Xylitol Biomanufacturing: Production Technologies, Industrial Applications and Future Opportunities

Abstract

Xylitol is a five-carbon sugar alcohol widely used in the food, pharmaceutical, oral healthcare, and personal care industries because of its low caloric value, low glycaemic index, and non-cariogenic properties. Industrial production is mainly based on catalytic hydrogenation of xylose, which provides high conversion efficiency but requires intensive energy input, costly catalysts, and complex purification processes. Microbial fermentation has emerged as a sustainable alternative for producing xylitol from renewable lignocellulosic biomass. This review summarizes recent advances in xylitol production, with a particular focus on microbial biomanufacturing. Key developments in lignocellulosic biomass utilization, metabolic engineering, cofactor balancing, oxygen regulation, and fermentation optimization are discussed. Chemical and biological production routes are critically compared in terms of efficiency, sustainability, and industrial applicability. Recent progress in downstream purification and biorefinery integration is also highlighted. Despite substantial advances, challenges including inhibitor toxicity, limited microbial robustness, low fermentation productivity, and high purification costs continue to hinder large-scale commercialization. Future research should focus on feedstock valorization, systems metabolic engineering, process intensification, and sustainable separation technologies to improve the economic and environmental sustainability of bio-based xylitol production.

1. Introduction

Changes in dietary habits and the growing preference for health-oriented products have intensified efforts to reduce free-sugar intake. Accordingly, the formulation of low-sugar and sugar-free foods has become an important research and development priority, particularly in the field of functional food ingredients [1,2]. This trend is driven by increasing evidence that excessive consumption of conventional caloric sweeteners, including sucrose, may contribute to dental caries, obesity, diabetes, metabolic syndrome, and other chronic diseases [3,4,5,6,7]. Therefore, considerable attention has been directed toward alternative sweeteners that can maintain acceptable sweetness while providing lower caloric density and a reduced glycemic impact.

Among these alternatives, xylitol is one of the most widely investigated sugar alcohols. Chemically, it is a five-carbon polyol with the molecular formula C₅H₁₂O₅ and the systematic name pentane-1,2,3,4,5-pentol [8]. Xylitol has a sweetness intensity similar to that of sucrose and produces a characteristic cooling sensation because of its negative heat of dissolution. From a nutritional perspective, it provides fewer calories and induces a lower glycemic response than sucrose. From an oral-health perspective, xylitol is not readily fermented by cariogenic microorganisms and consequently generates little acid in dental plaque. These combined physicochemical, sensory, metabolic, and anticariogenic properties account for its extensive application in sugar-free foods, chewing gums, confectionery products, pharmaceuticals, and oral-care formulations [7,9].

Among commercially important sugar alcohols, xylitol is distinguished by its balanced sensory, nutritional, and technological properties. Compared with sorbitol, maltitol, erythritol, and mannitol, it provides a combination of sweetness close to that of sucrose, low cariogenic potential, a characteristic cooling sensation, and compatibility with diverse food and oral-care formulations [10]. Its anticariogenic value is associated with several complementary mechanisms. Xylitol reduces the production of organic acids in dental plaque, interferes with the metabolism and growth of cariogenic bacteria, and can limit the formation or maturation of microbial biofilms. It also stimulates salivary flow, thereby enhancing acid clearance, buffering capacity, and the recovery of plaque pH [11]. These properties account for its extensive use in sugar-free chewing gum, lozenges, confectionery products, toothpaste, mouthwash, and oral sprays [12].

The functional relevance of xylitol is no longer confined to sweetness replacement and oral-health applications. As a humectant and moisture-regulating agent, it contributes to water retention, texture, and product stability in food, pharmaceutical, cosmetic, and personal-care formulations. Experimental studies have additionally reported antibacterial and antibiofilm effects, prompting investigation of its potential use in microbial control and tissue-protective formulations. More recent research has extended to possible effects on gut-microbiota composition, applications in ear, nose, and throat care, improvement of skin hydration and barrier function, and modification of the physicochemical properties of bio-based materials [13,14]. However, these emerging applications are supported by evidence of varying maturity, and their broader adoption will depend on further mechanistic studies, clinical validation, formulation optimization, and assessment of dose-dependent effects. The diversification of xylitol applications has been accompanied by continued commercial growth. Xylitol is now used across the food and beverage, pharmaceutical, nutraceutical, oral-care, cosmetics, and personal-care industries. Its relatively low caloric value, limited glycemic impact, oral-health relevance, and versatile formulation properties have contributed to its positioning as a high-value functional ingredient. A market report published in 2026 estimated that the global xylitol market reached USD 1.05 billion in 2025 and projected an increase to USD 1.48 billion by 2034, equivalent to a compound annual growth rate of approximately 3.82% during 2026–2034 [15]. The projected expansion is primarily associated with growing demand for low-calorie sweeteners, sugar-free foods, and health-oriented formulations, although market estimates should be interpreted as commercial forecasts rather than independently validated scientific data.

Quantitative application data further highlight the commercial significance of xylitol, particularly in the food and beverage sector. Recent industry data indicate that the food and beverage segment of the global xylitol market was valued at approximately USD 810 million in 2025, accounting for 39.5% of the total market [16]. This segment is also projected to continue expanding, driven by sugar-reduction reformulation and the development of sugar-free or low-calorie products. Typical food and beverage applications include sugar-free chewing gum, confectionery, bakery products, beverages, and diabetic-friendly formulations. Beyond food applications, xylitol is also used in pharmaceutical and nutraceutical products, including oral dosage forms, medicated confectionery, coating applications, dietary supplements, and medical nutrition products. Its established use in oral-care products, such as toothpaste, mouthwash, and dental chewing gum, together with its emerging use in cosmetics and personal-care formulations, further demonstrates its commercial relevance across multiple industrial sectors [16].

Xylitol occurs naturally in fruits, vegetables, berries, mushrooms, oats, and woody plant tissues, but only at low levels. Direct extraction is therefore unsuitable for industrial production. Therefore, the growing market demand and broad downstream utilization of xylitol make the development of efficient, stable, and economically feasible production technologies particularly important. Commercial xylitol production still depends largely on chemical synthesis [17]. This route usually starts from lignocellulosic resources rich in xylan or pentosans, such as corncobs, birch chips, and sugarcane bagasse. Hydrolysis releases xylose, which is then converted to xylitol by metal-catalyzed hydrogenation under high temperature and high pressure. This process has laid the foundation for industrial xylitol production. Its strengths include mature technology, a well-defined reaction pathway, relatively high conversion efficiency, and extensive scale-up experience. Yet it also raises clear sustainability concerns. High energy demand, harsh reaction conditions, dependence on metal catalysts, and complex separation and purification steps remain major barriers to greener process development [18].

Green manufacturing and biomass valorization are reshaping xylitol production. Biotechnological production offers a more sustainable option. This route uses microbial cells or intracellular oxidoreductase systems to selectively reduce D-xylose derived from lignocellulosic hemicellulose into xylitol. The process can proceed under relatively mild conditions and reduces the need for high-pressure hydrogen and metal catalysts [19]. A wide range of agricultural, forestry, and industrial by-products can serve as feedstocks. These include corncobs, sugarcane bagasse, rice straw, rice husks, fruit peels, nutshells, olive pomace, and industrial xylose mother liquor [20]. Even so, broad industrial application remains challenging. Hydrolysate inhibitors, limited strain robustness, difficult control of oxygen supply and redox balance, low fermentation intensity, and high downstream purification costs remain major barriers. Addressing these issues is essential for the green biomanufacturing of xylitol.

Although previous reviews have examined xylitol production, bioconversion, health benefits, or specific applications, most have focused on individual aspects, such as lignocellulosic feedstocks, microbial fermentation, oral-health effects, or food-related uses. A broader framework that connects the functional value of xylitol with its production technologies, industrial constraints, commercial relevance, and emerging applications remains limited. This review addresses this gap by integrating the physicochemical and functional properties of xylitol with its major production routes, including catalytic chemical synthesis and biotechnological conversion. These routes are critically compared in terms of feedstock requirements, process principles, technological maturity, environmental implications, technical advantages, and current limitations. Particular attention is given to microbial strain development, fermentation optimization, inhibitor tolerance, downstream separation and purification, and the challenges associated with industrial scale-up.

The review further evaluates established and emerging applications of xylitol in foods, oral-care products, pharmaceuticals, nutraceuticals, cosmetics, personal-care formulations, and other industrial fields, while also considering safety, market demand, and patterns of commercial utilization. Finally, future opportunities are discussed in the context of green manufacturing, integrated biorefineries, efficient product recovery, functional product design, and evidence-based safety evaluation. By linking molecular properties and biological functions with manufacturing feasibility and market needs, this review provides a comprehensive perspective on xylitol as both a multifunctional ingredient and a value-added bio-based product, and identifies priorities for its sustainable production and high-value industrial development.

2. Basic Properties of Xylitol

2.1. Physicochemical Properties and Functional Characteristics

Xylitol is a five-carbon sugar alcohol with the molecular formula C₅H₁₂O₅ and a relative molecular mass of 152.15 [21]. It occurs widely in various biomass resources, including fruits, vegetables, berries, mushrooms, oats, and woody plant tissues [22]. It can also exist as a low-abundance intermediate in the alternative pathway of human glucose metabolism. Xylitol is highly soluble in water. Its dissolution absorbs heat, which gives a mild cooling sensation in the mouth. It is slightly soluble in ethanol and methanol and usually appears as white crystals or a crystalline powder. Its melting point is approximately 92–96 °C, and its boiling point can reach 216 °C. The pH of a 10% aqueous solution is about 5.0–7.0. Xylitol also shows good thermal stability and does not participate in the Maillard reaction.

Xylitol has a sweetness close to that of sucrose. It can therefore be widely used as a sweetener in sugar-free food systems [23]. Previous studies have shown that xylitol is not readily fermented by cariogenic oral bacteria. It reduces acid production in dental plaque and helps lower the risk of dental caries [24,25,26]. Compared with sucrose, xylitol has a lower energy value. It is commonly reported to provide about 2.4 kcal/g, whereas sucrose provides about 4 kcal/g [27]. In addition, xylitol has a lower glycemic index and induces a weaker insulin response than glucose and sucrose. As a low-glycemic sugar alcohol, xylitol has advantages in reducing postprandial glycemic load and replacing conventional sugars. It serves both as a sugar substitute and as a functional food ingredient. For this reason, xylitol is considered a promising sweetener for dietary management in diabetes. It may be particularly useful as a practical alternative to sucrose for reducing sugar intake in patients with type 2 diabetes [28,29].

Xylitol not only a low-calorie sweetener but also has certain physiological regulatory effects. Studies suggest that it may help improve liver function, support liver protection, and participate in lipid metabolism regulation. It is therefore suitable for use as a nutritional health ingredient in the development of functional products [30]. In addition, xylitol has good hygroscopic and water-retention properties. It can be used as a moisture-regulating agent and antifreeze humectant. With these functional features, xylitol has considerable application value and development potential in the food, pharmaceutical, and chemical industries [31,32].

2.2. Comparison of Xylitol with Other Sweeteners and Sugar Alcohols

Table 1 summarizes the main differences between xylitol and several common sugar alcohol sweeteners. Xylitol, sorbitol, maltitol, erythritol, and mannitol all belong to the sugar alcohol family. Yet they differ in sweetness quality, metabolic fate, gastrointestinal tolerance, and effects on the oral microbiota [33]. Erythritol is low in calories and is mainly absorbed unchanged before urinary excretion. Sorbitol and maltitol offer advantages in raw material availability and production cost. They are therefore widely used in the food industry. However, their sensory properties, glycemic effects, and intestinal tolerance are not the same as those of xylitol.

The main strengths of xylitol are its sucrose-like sweetness and its well-defined oral health benefits. Existing studies and product applications show that xylitol can inhibit cariogenic bacterial metabolism, reduce acid production in dental plaque, and help maintain oral health [34]. Thus, among sugar alcohol sweeteners, xylitol has strong overall application value. It combines sensory compatibility with functional benefits and is well suited for the development of sugar-free foods and oral care products [35,36].

Table 1. Comparative functional characteristics of xylitol and selected sugar alcohols.

Sugar Alcohol	Relative Sweetness	Energy Value/Glycemic Response	Oral-Health Relevance	Processing and Tolerance Characteristics
Xylitol	Approximately equivalent to sucrose [37]	Approximately 2.4 kcal/g; low glycemic response [38].	Not readily fermented by cariogenic bacteria to produce acids; closely associated with studies on Streptococcus mutans, dental plaque, and caries prevention using chewing gum [36,39,40].	Pronounced cooling sensation; excessive intake may cause bloating and diarrhea; toxic to dogs [41,42].
Sorbitol	Approximately 50–70% as sweet as sucrose [43]	Approximately 2.6 kcal/g; relatively low GI [44].	Low cariogenicity, although some oral microorganisms may utilize it slowly; frequently used as a reference sugar alcohol.	Strong humectant properties; commonly used in confectionery and oral-care products; gastrointestinal tolerance requires attention [45].
Erythritol	Approximately 60–80% as sweet as sucrose	Nearly 0 kcal/g; GI close to 0 [46].	Non-cariogenic; generally shows better gastrointestinal tolerance than xylitol [47].	Most is absorbed in the small intestine and excreted unchanged in urine; cardiovascular risk has also been discussed in recent studies.
Maltitol	Approximately 75–90% as sweet as sucrose [48]	Nearly 2.1 kcal/g, but GI is higher than that of most monosaccharide sugar alcohols.	Low cariogenicity, but its postprandial glycemic effect is higher than that of xylitol and erythritol.	Suitable for chocolate, bakery products, and confectionery; excessive intake may have a laxative effect [49].
Mannitol [50]	Approximately 50–70% as sweet as sucrose	About 1.6 kcal/g; glycemic and insulin indices close to 0 [51]	Non-cariogenic; not readily fermented by oral bacteria to produce acids; commonly used in sugar-free chewing gum [52]	Non-reducing and does not readily undergo Maillard reactions, helping preserve product color; improves stability and texture in chewing gum, ice cream, chocolate, and bakery products; generally well tolerated, although excessive intake may cause gastrointestinal discomfort or diarrhea
Arabitol	Reported sweetness varies with stereoisomer and formulation; generally regarded as a sweet-tasting pentitol, although standardized relative-sweetness data remain limited.	Its physiological energy value and glycemic response have not been as systematically established as those of commercially established polyols such as xylitol, erythritol, and sorbitol.	Potential non-cariogenic properties have been discussed, but direct clinical and oral-health evidence remains limited compared with xylitol and erythritol [53].	A five-carbon polyol and stereoisomer of xylitol; can be produced by yeasts and fungi from sugars or renewable carbon sources; currently more relevant as a biotechnological product and platform chemical than as a widely used bulk sweetener. Excess-intake tolerance data remain limited.
Lactitol	Approximately 30–40% as sweet as sucrose [54].	Approximately 2 kcal/g; poorly absorbed in the small intestine and generally produces a low postprandial glycemic response.	Low cariogenic potential because it is not readily fermented to acids by oral microorganisms; may help reduce tooth demineralization when replacing fermentable sugars.	Produced by catalytic hydrogenation of lactose; used as a bulk sweetener, texturizer, and pharmaceutical excipient. Its low hygroscopicity is advantageous in moisture-sensitive products. Excessive intake may cause abdominal discomfort, flatulence, or a laxative effect.

Table 1. Comparative functional characteristics of xylitol and selected sugar alcohols.

Sugar Alcohol	Relative Sweetness	Energy Value/Glycemic Response	Oral-Health Relevance	Processing and Tolerance Characteristics
Xylitol	Approximately equivalent to sucrose [37]	Approximately 2.4 kcal/g; low glycemic response [38].	Not readily fermented by cariogenic bacteria to produce acids; closely associated with studies on Streptococcus mutans, dental plaque, and caries prevention using chewing gum [36,39,40].	Pronounced cooling sensation; excessive intake may cause bloating and diarrhea; toxic to dogs [41,42].
Sorbitol	Approximately 50–70% as sweet as sucrose [43]	Approximately 2.6 kcal/g; relatively low GI [44].	Low cariogenicity, although some oral microorganisms may utilize it slowly; frequently used as a reference sugar alcohol.	Strong humectant properties; commonly used in confectionery and oral-care products; gastrointestinal tolerance requires attention [45].
Erythritol	Approximately 60–80% as sweet as sucrose	Nearly 0 kcal/g; GI close to 0 [46].	Non-cariogenic; generally shows better gastrointestinal tolerance than xylitol [47].	Most is absorbed in the small intestine and excreted unchanged in urine; cardiovascular risk has also been discussed in recent studies.
Maltitol	Approximately 75–90% as sweet as sucrose [48]	Nearly 2.1 kcal/g, but GI is higher than that of most monosaccharide sugar alcohols.	Low cariogenicity, but its postprandial glycemic effect is higher than that of xylitol and erythritol.	Suitable for chocolate, bakery products, and confectionery; excessive intake may have a laxative effect [49].
Mannitol [50]	Approximately 50–70% as sweet as sucrose	About 1.6 kcal/g; glycemic and insulin indices close to 0 [51]	Non-cariogenic; not readily fermented by oral bacteria to produce acids; commonly used in sugar-free chewing gum [52]	Non-reducing and does not readily undergo Maillard reactions, helping preserve product color; improves stability and texture in chewing gum, ice cream, chocolate, and bakery products; generally well tolerated, although excessive intake may cause gastrointestinal discomfort or diarrhea
Arabitol	Reported sweetness varies with stereoisomer and formulation; generally regarded as a sweet-tasting pentitol, although standardized relative-sweetness data remain limited.	Its physiological energy value and glycemic response have not been as systematically established as those of commercially established polyols such as xylitol, erythritol, and sorbitol.	Potential non-cariogenic properties have been discussed, but direct clinical and oral-health evidence remains limited compared with xylitol and erythritol [53].	A five-carbon polyol and stereoisomer of xylitol; can be produced by yeasts and fungi from sugars or renewable carbon sources; currently more relevant as a biotechnological product and platform chemical than as a widely used bulk sweetener. Excess-intake tolerance data remain limited.
Lactitol	Approximately 30–40% as sweet as sucrose [54].	Approximately 2 kcal/g; poorly absorbed in the small intestine and generally produces a low postprandial glycemic response.	Low cariogenic potential because it is not readily fermented to acids by oral microorganisms; may help reduce tooth demineralization when replacing fermentable sugars.	Produced by catalytic hydrogenation of lactose; used as a bulk sweetener, texturizer, and pharmaceutical excipient. Its low hygroscopicity is advantageous in moisture-sensitive products. Excessive intake may cause abdominal discomfort, flatulence, or a laxative effect.

Beyond their functional characteristics, sugar alcohols also differ in their production routes. Commercial production generally relies on the catalytic hydrogenation of the corresponding sugars, whereas biotechnological production uses selected microorganisms under relatively mild conditions. Mannitol, arabitol, and erythritol are representative sugar alcohols that can be produced through microbial conversion, and glycerol may serve as a renewable carbon source or co-substrate in some microbial processes. These biotechnological routes provide potential advantages in terms of renewable feedstock utilization and mild processing conditions, although their practical application still depends on microbial conversion efficiency, product yield, process stability, and downstream purification requirements.

3. Production Processes of Xylitol

Based on the expanding demand and broad industrial application of xylitol, the development of efficient, stable, and economically feasible production processes is essential for supporting its large-scale utilization. At present, industrial xylitol is mainly produced through chemical synthesis and biotechnological methods. The following section summarizes the major technical routes, process characteristics, and key limitations associated with these production strategies.

3.1. Chemical Synthesis

Chemical catalytic synthesis remains one of the core routes for industrial xylitol production [17]. This process uses agricultural and forestry lignocellulosic materials rich in pentosans or xylan, such as corncobs, birch wood chips, and sugarcane bagasse, as feedstocks [18,55]. After hydrolysis, the hemicellulose fraction is degraded and releases a xylose-rich sugar liquor [56,57]. However, the hydrolysate is not a pure xylose system. It usually contains other monosaccharides, including glucose, galactose, and arabinose, as well as non-sugar impurities such as organic acids, sugar degradation products, and lignin-derived phenolic compounds [58].

These complex components can interfere with hydrogenation and increase the burden of downstream purification. Efficient purification is therefore a prerequisite for chemical xylitol production. After multistep purification, the high-purity xylose solution is hydrogenated under high temperature and high pressure using Raney nickel as the catalyst. The reaction liquor is then refined through catalyst removal, concentration, decolorization, desalting, chromatographic separation, and low-temperature crystallization. High-purity xylitol crystals are finally obtained [59].

Thus, chemical synthesis is based on high-purity xylose, uses catalytic hydrogenation for targeted conversion, and depends on precise downstream processing to ensure product quality. This route is mature, technically clear, and remains an important basis for chemical xylitol production [19,60]. The basic reaction process is shown in Figure 1.

In terms of process maturity, chemical catalysis offers several advantages. These include a well-defined reaction pathway, high product selectivity, well-established process control, and a solid basis for continuous or semi-continuous scale-up. For these reasons, it has long played a central role in industrial xylitol production. In recent years, many catalytic systems have been developed to reduce the use of noble metals, improve the activity and stability of non-noble metal catalysts, enhance compatibility with aqueous-phase reactions, and promote continuous operation. Representative systems include Co/SiO₂ catalysts [62], Ni–Re bimetallic nanoparticle catalysts [63], Ni₃Fe bimetallic nanocatalysts in choline chloride-based media [64], phyllosilicate-derived Cu–Ni alloy catalysts [65], Cu–Ni/SiO₂ bimetallic catalysts [66], Cu@C catalysts [67], solid foam-supported catalysts [68], Ru/TiO₂ catalysts [69,70], and Ru catalysts supported on mesoporous silica-alumina [71,72]. These studies show that high xylose conversion and high xylitol selectivity can be achieved at relatively high xylose concentrations by regulating metal-support interactions, bimetallic synergy, and pore structure. They also provide an important basis for reducing reaction severity, improving catalyst reusability, and upgrading the chemical synthesis process for xylitol [73]. In this review, xylose conversion, xylitol yield, xylitol selectivity, reaction time, catalyst recyclability, and catalyst stability are used as key indicators for evaluating the performance of chemical catalytic systems. Representative chemical catalytic systems and their reported performances are summarized in

Table 2. Representative chemical production methods and catalytic systems for xylitol production.

Chemical Approach/Catalytic System	Typical Substrate or Operating Feature	Representative TRY-Related Performance	Main Advantages	Main Limitations	References
Conventional Raney Ni or Ni-based hydrogenation	Purified or highly concentrated xylose solution; elevated temperature and H2 pressure	High industrial reliability, but detailed public TRY values are often not disclosed for commercial processes	Mature unit operations; relatively low catalyst cost; established scale-up experience	Requires high-pressure H2 and purified xylose; Ni leaching, catalyst deactivation, metal residues, and complex purification remain concerns	[62,63]
Co/SiO2 catalytic hydrogenation	Xylose hydrogenation in water over silica-supported cobalt catalyst	Optimized xylitol yield up to 98%; selectivity remained nearly unchanged after four reuse cycles, although moderate deactivation occurred	Uses non-noble cobalt; high yield in water; promising selectivity	Catalyst deactivation and long-term stability require further improvement; validation with real hydrolysates remains limited	[62]
Ni-Re/AC bimetallic catalyst	Aqueous-phase xylose hydrogenation; activated-carbon-supported Ni-Re catalyst	Xylitol yield up to 98.0% at 140 °C for 1 h; hemicellulosic hydrolysate gave high xylose conversion and xylitol yield	Re improves Ni dispersion, activity, and leaching resistance; suitable for hydrolysate testing	Re cost, catalyst recyclability, impurity tolerance, and long-term stability need further assessment	[63]
Ni3Fe catalyst in choline chloride-based medium	High-concentration xylose/choline chloride system; transition-metal alloy catalyst	Approximately 80% xylitol yield from 76 wt.% xylose under optimized conditions; conversion and yield decreased during recycling	Allows high substrate concentration; avoids precious metals; choline chloride medium may improve substrate handling	Catalyst deactivation by adsorbed organic species; recycling stability limited; solvent recovery and viscosity need evaluation	[64]
Cu-Ni/SiO2 bimetallic catalyst	Catalytic hydrogenation of xylose over supported Cu-Ni catalyst	96% xylose conversion and >99% xylitol selectivity reported under optimized conditions	Non-noble bimetallic system; high selectivity; improved interaction between Cu, Ni, and support	Need long-term continuous testing, metal-leaching data, and evaluation with real hydrolysates	[66]
Phyllosilicate-derived Cu-Ni alloy catalyst	High-concentration xylose aqueous solution hydrogenation	Designed for efficient hydrogenation of high-concentration xylose solutions	Enhanced alloy dispersion and catalytic activity; relevant to process intensification	Further data needed on catalyst lifetime, hydrolysate impurities, continuous operation, and TEA/LCA	[65]
Electrocatalytic xylose reduction	Electrocatalytic hydrogenation on roughened metal electrodes using electricity and water as hydrogen source	Roughened Cu/Ag-type systems showed xylitol formation, but conversion and selectivity were lower than mature thermal hydrogenation systems; xylitol selectivity up to 67.1% at 30.8% xylose conversion has been reported	Mild temperature and pressure; potential coupling with renewable electricity; avoids external high-pressure H2	Low current density, Faradaic efficiency, conversion, selectivity, electrode stability, and downstream separation remain major barriers	[74]
One-pot hydrolytic hydrogenation of xylan	Bifunctional acid-metal catalytic systems integrating xylan hydrolysis and hydrogenation	PTA_Ru/CTF3 achieved 88% xylan conversion and up to 80% xylitol selectivity, with stability over six recycling runs	Integrates hydrolysis and hydrogenation; may reduce intermediate xylose purification	Requires balance of acid and metal functions; sugar degradation, catalyst leaching, impurity tolerance, and scale-up remain challenging	[75]

.

The comparison in Table 2 indicates that conventional catalytic hydrogenation still provides the highest maturity and the most reliable product consistency. Co/SiO₂, Ni–Re/AC, Ni₃Fe, and Cu–Ni catalysts have all improved catalytic performance relative to traditional Raney Ni systems, but their advantages are not identical. Co/SiO₂ and Ni–Re/AC provide high yield in aqueous xylose hydrogenation, whereas Ni₃Fe in choline chloride-based media is attractive for high-concentration xylose processing. Cu-Ni systems reduce dependence on noble metals and can provide very high xylitol selectivity.

However, conventional chemical synthesis still has several limitations that cannot be ignored. First, catalytic hydrogenation of xylose usually requires external hydrogen and is conducted at elevated temperature and pressure. This places high demands on reactor design, energy consumption, hydrogen supply, and safety control [76]. Second, the reaction often relies on metal catalysts such as Raney Ni, Ni-based catalysts, or Ru-based catalysts [77,78]. The cost of catalyst preparation, leaching of active metals, deactivation caused by carbon deposition or impurity poisoning, catalyst regeneration and disposal, and control of metal residues in the final product all increase the burden of production and downstream processing [76].

In addition, acid hydrolysis and subsequent refining may generate by-products or inhibitory impurities, including furfural, 5-hydroxymethylfurfural, organic acids, phenolic compounds, pigments, and inorganic salts. These components complicate xylose liquor purification, xylitol crystallization, and mother liquor recycling. They also increase the pressure on wastewater treatment and environmental management [79]. Therefore, although chemical catalysis has the advantages of mature technology, relatively high conversion efficiency, and a well-established basis for industrial scale-up, its high energy demand, strict equipment requirements, multistep refining process, and environmental burden limit its further development in the context of green manufacturing and sustainable production.

3.2. Biotechnological Production

Biotechnological production offers a more sustainable route for xylitol production. Its core principle is to use microbial cells or intracellular oxidoreductase systems to selectively reduce D-xylose released from lignocellulosic hemicellulose into xylitol [18]. Unlike chemical hydrogenation, this process is usually performed at mild temperatures and under atmospheric or low-pressure conditions. It does not depend on high-pressure hydrogen or metal catalysts. As a result, it can reduce metal residues, lower safety risks, and lessen the environmental pressure caused by harsh reaction conditions. Another advantage of this route is its broad feedstock base. Renewable resources such as corncobs, sugarcane bagasse, rice straw, rice husks, fruit peels, nutshells, olive pomace, and industrial xylose mother liquor can all be used as substrate sources [21,80]. These materials are rich in xylan or xylose and are well suited for integration with second-generation biorefinery systems. In this sense, biotechnological production is not only a method for preparing xylitol. It is also a green manufacturing strategy for upgrading agricultural wastes into higher-value products [81,82].

Biotechnological xylitol production is a systems-level process rather than a single fermentation step. Figure 2 summarizes the overall biotechnological process for xylitol production from lignocellulosic biomass, including feedstock utilization, pretreatment, detoxification, microbial conversion, and downstream recovery. Among these steps, biomass pretreatment is particularly critical because it determines hemicellulose deconstruction efficiency, xylose recovery, inhibitor formation, and the subsequent fermentability of the hydrolysate. An ideal pretreatment for xylitol production should selectively release xylose from hemicellulose while minimizing sugar degradation, lignin-derived inhibitors, acid neutralization requirements, and downstream detoxification costs. Therefore, pretreatment performance should be evaluated not only by total sugar release, but also by xylose yield, inhibitor concentration, cellulose retention, wastewater generation, and compatibility with xylitol-producing microorganisms.

The front end of this process focuses on disrupting the lignocellulosic structure, enabling selective hemicellulose depolymerization and efficient xylose release [83]. Dilute acid, hydrothermal treatment, steam explosion [84], enzymatic treatment, combined acid–enzyme treatment, and green solvent-based pretreatment can all serve this purpose. Dilute acid pretreatment remains one of the most effective and widely used strategies for hemicellulose solubilization because it can achieve high xylose recovery under relatively simple operating conditions. For example, optimized dilute sulfuric acid pretreatment of corn stover has been reported to achieve approximately 82.8% xylan hydrolysis and to provide a fermentable hydrolysate that supported xylitol production of 10.9 g/L with a conversion yield of 0.97 g/g without additional detoxification or nutrient supplementation [85]. These results indicate that dilute acid pretreatment can be highly suitable for xylitol production when inhibitor formation is properly controlled. However, its limitations are also evident. Acid-catalyzed reactions can promote the formation of furfural, 5-hydroxymethylfurfural, acetic acid, and lignin-derived phenolic compounds. They may also cause equipment corrosion, increase neutralization costs, and generate additional wastewater treatment burdens [86,87,88].

Hydrothermal or liquid hot water pretreatment provides a less corrosive alternative because it uses water as the reaction medium and avoids the addition of mineral acids. This method can improve hemicellulose solubilization and reduce chemical input, making it attractive from an environmental perspective [89]. Nevertheless, hydrothermal pretreatment often requires relatively high temperature and pressure, and the resulting hydrolysate may contain lower xylose concentrations because of dilution effects. Therefore, it is more suitable when chemical-free operation and reduced equipment corrosion are prioritized, but further concentration or process integration may be needed to improve fermentation efficiency [90]. Steam explosion is another scalable pretreatment technology with potential relevance to xylitol production. It combines hydrothermal disruption with rapid pressure release and can be applied to various agricultural residues [91,92]. In a multi-feedstock optimization study, steam explosion generated xylose-rich hydrolysates containing approximately 75–95% of the xylose originally present in the biomass, while inhibitor levels remained within a range compatible with microbial conversion to xylitol [93]. Its advantages include scalability, relatively short residence time, and partial preservation of cellulose and lignin in the solid fraction. However, xylose release and inhibitor formation are highly sensitive to pressure, residence time, catalyst loading, and feedstock type. Acid-impregnated steam explosion may still suffer from corrosion and inhibitor-related problems.

Enzymatic and combined acid–enzyme pretreatments offer another strategy for improving process selectivity [94]. Enzymatic hydrolysis can operate under mild conditions and generate fewer degradation products, which is favorable for subsequent fermentation. However, enzyme cost, reaction time, substrate accessibility, and the need for effective upstream delignification limit its direct application as a stand-alone pretreatment [95]. Combined acid–enzyme strategies may improve overall sugar recovery by using acid pretreatment to release hemicellulosic xylose and enzymatic hydrolysis to further utilize residual polysaccharides. Such integrated approaches are particularly useful when xylitol production is designed as part of a broader biorefinery process that also valorizes cellulose-derived glucose or residual lignin.

Biological pretreatment may further complement enzymatic and combined pretreatment strategies by facilitating lignin removal prior to hydrolysis. In particular, white-rot fungi are known for their ability to secrete oxidative enzymes that contribute to lignin modification and degradation, thereby improving the accessibility of cellulose and hemicellulose and favoring the subsequent release of glucose and xylose. Representative ligninolytic enzymes include laccase, lignin peroxidase, and manganese peroxidase, while several other oxidative enzymes may also participate in this process. However, compared with physicochemical pretreatment technologies, fungal pretreatment generally requires longer processing times and remains less widely applied in industrial xylitol production.

Recent advances in green pretreatment technologies have focused mainly on ionic liquids, deep eutectic solvents, organic acid-based systems, and other recyclable solvent platforms [96]. Deep eutectic solvents are especially attractive because they are tunable, have low vapor pressure, can promote delignification, and may improve the accessibility of hemicellulose and cellulose [97]. For instance, sequential pretreatment using a choline chloride deep eutectic solvent followed by CuCl₂ treatment of oil palm fronds produced a hydrolysate containing 14.76 g/L xylose, which was approximately 25% higher than that obtained with CuCl₂-only pretreatment [98]. This indicates that deep eutectic solvent-assisted pretreatment can enhance xylose recovery and lignocellulose fractionation. More recent deep eutectic solvent-based strategies also attempt to reduce washing steps and water consumption through one-pot or process-intensified designs. However, high solvent viscosity, solvent cost, incomplete solvent recovery, possible solvent residues, inhibition of enzymatic saccharification or microbial fermentation, and scale-up uncertainty remain major barriers to industrial application. Ionic liquids and organic solvent systems can also improve biomass fractionation, but their practical use for xylitol production depends on solvent recyclability, toxicity, cost, and compatibility with downstream fermentation [99].

Overall, each pretreatment method has a different suitability profile for xylitol production. Dilute acid pretreatment is efficient for xylose release but requires careful control of inhibitor formation, corrosion, and neutralization burden. Hydrothermal pretreatment reduces chemical input but may generate dilute sugar streams. Steam explosion is scalable and effective for biomass disruption, but its selectivity depends strongly on operating severity and feedstock type. Enzymatic and combined pretreatments provide higher selectivity and lower inhibitor formation, but enzyme cost and reaction time remain concerns. Green solvent-based pretreatments, particularly deep eutectic solvent systems, show promise for selective fractionation and improved xylose recovery, but their economic feasibility, solvent recycling, biological compatibility, and scale-up stability need further validation [100]. Future studies should compare pretreatment technologies using unified indicators, including xylose recovery, inhibitor concentration, hydrolysate fermentability, detoxification demand, water and energy consumption, and total process cost, rather than evaluating sugar release alone.

Hemicellulosic hydrolysates obtained after pretreatment are usually rich in xylose. However, they also contain complex components, including arabinose, glucose, galactose, acetic acid, furfural, 5-hydroxymethylfurfural, phenolic compounds, inorganic salts, and pigments [82,101]. These inhibitors can reduce xylitol yield and production intensity through several mechanisms. For example, they have been reported to damage cell membrane integrity, interfere with xylose transport, inhibit key enzyme activities, and disturb intracellular redox balance and energy metabolism [102]. Therefore, the hydrolysate often needs to be concentrated, decolorized, desalted, and detoxified before fermentation. Several methods have been used to improve the fermentability of hydrolysates. These include activated carbon adsorption, ion exchange, overliming, vacuum evaporation, nanofiltration/reverse osmosis membrane separation, enzymatic degradation, and biological detoxification [103,104]. However, stronger detoxification is not always better. Excessive treatment may cause xylose loss and increase material consumption and wastewater burden. A more rational process goal is to reduce inhibitor concentrations below the tolerance threshold of the production strain, while maximizing xylose retention and minimizing the overall downstream cost [105].

The basic reaction process is shown in Figure 3. From a metabolic perspective, xylitol accumulation depends on the balance among xylose uptake, reduction, and subsequent oxidative diversion. After D-xylose enters the cell, it is first reduced to xylitol by xylose reductase (XR), using NADPH or NADH as the reducing cofactor [106,107]. Xylitol can then be oxidized to xylulose by xylitol dehydrogenase (XDH) [106,107]. Subsequently, xylulose is phosphorylated by xylulokinase (XK) to form xylulose-5-phosphate (X5P), which serves as the key intermediate linking xylose metabolism to central carbon metabolism [108]. X5P is primarily assimilated through the non-oxidative pentose phosphate pathway (PPP), where transketolase (TKT) and transaldolase (TAL) catalyze a series of reversible carbon rearrangement reactions, generating fructose-6-phosphate and glyceraldehyde-3-phosphate that subsequently enter glycolysis and biosynthetic pathways [108]. In certain bacteria and non-conventional microorganisms, X5P may also be metabolized through the phosphoketolase (PK) pathway, producing glyceraldehyde-3-phosphate and acetyl phosphate, thereby providing an alternative route for carbon utilization and ATP generation [109]. The distribution of intracellular carbon flux between the PPP and phosphoketolase pathway strongly influences cofactor regeneration, biomass formation, and xylitol accumulation [17]. Consequently, enzymes such as XK, TKT, TAL, and phosphoketolase have become important targets for metabolic engineering aimed at improving xylose utilization efficiency and xylitol productivity [19].

Therefore, improving xylitol accumulation is not simply a matter of increasing cell growth. It requires an appropriate metabolic state that balances XR catalytic efficiency, XDH activity, cofactor supply, oxygen level, and carbon flux distribution through the coordinated regulation of xylose assimilation and downstream pentose metabolism [110,111]. Oxygen supply is a key engineering parameter in xylitol fermentation. Moderate microaerobic conditions help maintain cell activity and cofactor regeneration. They also limit the excessive oxidation of xylitol to xylulose, allowing more metabolic flux to remain at the xylitol-forming stage. In contrast, excessive oxygen supply promotes further oxidation of xylitol and directs carbon toward growth and energy metabolism. Insufficient oxygen, however, may suppress cell activity, xylose transport, and reducing power regeneration.

This pattern has been verified to varying degrees in Candida [112], Pichia [113], Pichia/Komagataella, Kluyveromyces [114], and other non-conventional yeasts. Therefore, fermentation performance should be improved through the coordinated optimization of pH, temperature, initial xylose concentration, inoculum size, nitrogen supplementation, agitation and aeration, and volumetric oxygen transfer coefficient (kLa). These parameters should also be matched with the cofactor preference and inhibitor tolerance of the production strain to establish a stable process window [115,116,117].

Various filamentous fungi, yeasts, and bacteria can form xylitol through their natural metabolic processes. However, yeasts remain the most representative and industrially promising hosts in current studies on xylitol biomanufacturing [17]. Their main advantages include strong xylose-reducing capacity, tolerance to high osmotic pressure and acidic conditions, and good potential for process regulation and strain engineering. Xylitol accumulation in yeasts can be further improved through strategies such as oxygen-limited control, nutrient regulation, cell immobilization, adaptive evolution, and metabolic engineering.

Conventional strain screening and fermentation optimization have identified many xylitol-producing yeasts, including Candida [118], Pichia [119], Meyerozyma [120], Debaryomyces [121], Wickerhamomyces [122], Rhodotorula [123], Kluyveromyces [124], Barnettozyma [125], and Clavispora species [126]. These studies have clarified the importance of pH, temperature, aeration, agitation, nitrogen source, initial xylose concentration, cell immobilization, detoxification strategy, and fed-batch or airlift operation. However, conventional optimization mainly improves production performance by selecting naturally favorable phenotypes or adjusting extracellular process conditions [19]. It cannot fully resolve intracellular bottlenecks such as limited xylose uptake, insufficient reducing-power supply, xylitol reassimilation, and weak tolerance to hydrolysate-derived inhibitors. Therefore, metabolic engineering has become an increasingly important strategy for further improving xylitol titer, yield, productivity, substrate utilization, and hydrolysate tolerance [118].

Metabolic engineering strategies for xylitol production mainly focus on four constraints: xylose uptake, xylose-to-xylitol reduction, xylitol reassimilation, and intracellular reducing-power supply. First, heterologous expression or screening of efficient xylose reductases can increase the rate of xylose reduction to xylitol. Engineered hosts such as Escherichia coli [127], Saccharomyces cerevisiae [128], and Pichia pastoris [119] have been modified by introducing or strengthening XR genes from efficient xylose-utilizing microorganisms. Second, attenuation of XDH activity or downstream xylose-assimilation pathways can reduce the oxidation of xylitol to xylulose, thereby enhancing xylitol accumulation. Third, cofactor engineering can increase NADPH or NADH availability and adjust cofactor preference, which is essential because insufficient reducing power may limit XR activity. Fourth, transporter engineering can improve xylose uptake, especially under high-substrate-concentration or mixed-sugar hydrolysate conditions [129].

Representative engineering approaches include XR overexpression, screening of XR variants with improved catalytic efficiency, deletion or weakening of competing pathways, modification of native or heterologous xylose transporters, enhancement of NADPH regeneration, adaptive laboratory evolution, and stress-tolerance engineering. For example, engineered E. coli expressing xylose reductase from Zymomonas mobilis, together with cofactor-supply and transporter-engineering strategies, produced 88.4 ± 0.7 g/L xylitol with a yield of 0.95 g/g when the mutant glucose facilitator GlfL445I was used [127]. Another recombinant E. coli process produced 172.4 g/L xylitol after 110 h of fed-batch cultivation, with an average productivity of 1.57 g/L/h [130]. In industrial S. cerevisiae, overexpression of GRE3 enabled production of 148.5 g/L xylitol with a yield of 0.95 g/g from xylose-rich media [131]. In engineered Pichia pastoris, synthetic-pathway construction, pentose phosphate pathway enhancement, enzyme engineering, and XDH modification further expanded xylitol production from non-xylose carbon sources such as glucose, glycerol, and methanol [132]. These examples show that metabolic engineering can complement natural strain screening and process optimization by directly controlling intracellular carbon flux and redox balance.

To avoid repetition between natural strain screening studies and engineered high-performance systems,

Table 3. Comparison of representative natural yeasts, filamentous fungi, and engineered microbial platforms for xylitol production.

System Type	Representative Species/Strain	Engineering or Process Strategy	Typical Substrate or Reactor System	Xylitol Titer, Yield, and Productivity	Main Characteristics	Process Implications	References
Natural yeast/process optimization	Candida tropicalis/C. tropicalis GS18/MTCC 6192	Hydrolysate detoxification, fermentation optimization, and oxygen-limited conversion	Rice straw pentosan; areca nut husk enzymatic hydrolysate; mixed agricultural waste hydrolysate	25.15 g/L in non-detoxified rice straw hydrolysate and 34.21 g/L in detoxified rice straw hydrolysate using C. tropicalis GS18; 2.47–5.88 g/L in other agricultural hydrolysate systems	Strong xylose-reducing capacity and a well-established research basis; suitable for integrated studies on detoxification, fermentation, and crystallization	Suitable for xylose-rich hydrolysates; inhibitor tolerance and oxygen-limited control should be carefully considered	[133,134]
Natural yeast/real hydrolysate conversion	Candida guilliermondii FTI 20037	Reactor-scale fermentation using hemicellulosic hydrolysate	Olive-tree pruning residue hydrolysate	Yield and volumetric productivity of 0.37 kg kg−1 and 0.26 kg m−3 h−1, respectively	Capable of using real hydrolysates for co-production of ethanol and xylitol; suitable for scale-up-related studies	Nutrient supplementation, oxygen transfer, and reactor-scale effects need to be optimized	[135]
Natural yeast/intensified process	Pichia fermentans WC1507	Oxygen-limited fermentation and immobilized-cell/airlift reactor operation	High-concentration xylose medium; free-cell batch and immobilized-cell airlift systems	79.4 g/L in free-cell batch fermentation; 63.0 g/L in an immobilized-cell/airlift reactor system	High xylitol titers under oxygen-limited, pH-controlled, and appropriate nitrogen-source conditions; cells can be immobilized using alginate or mycelial-pellet carriers	Immobilization supports cell reuse, but mass-transfer limitation should be avoided	[115]
Natural filamentous fungus (Zygomycetes)	Thamnidium elegans CCF-1465	Wild-type fungal fermentation	Commercial D-xylose (100 g/L) in shake-flask culture	31.1 g/L xylitol after approximately 240 h; xylitol production increased with increasing xylose concentration	Native xylose metabolism with efficient xylitol secretion; simultaneous production of microbial lipids and xylitol	Demonstrates that filamentous fungi can serve as alternative natural xylitol producers and potential chassis for future metabolic engineering	[17,136]
Natural filamentous fungus (Zygomycetes)	Mortierella (Umbelopsis) isabellina ATHUM 2935	Wild-type fungal fermentation	Commercial D-xylose (80 g/L) under nitrogen-limited shake-flask cultivation	24.0 g/L xylitol; yield ≈ 0.35 g/g xylose consumed	Carbon flux is naturally redirected toward xylitol instead of lipid accumulation during xylose metabolism	Represents a promising non-conventional fungal platform for studying carbon partitioning and future strain improvement	[19,137]
Tolerant yeast/adaptive evolution	Wickerhamomyces anomalus Z1/ALE	Adaptive laboratory evolution for hydrolysate-inhibitor tolerance	Sugarcane bagasse hemicellulosic hydrolysate	13.41 g/L using 75% deacetylated sugarcane bagasse hydrolysate	Adaptive laboratory evolution can improve tolerance to pretreatment-derived inhibitors	Suitable for coupling mild detoxification with tolerant-strain adaptation	[138]
Natural yeast/complex hydrolysate conversion	Debaryomyces hansenii	Nanofiltration detoxification and nutrient supplementation	Dilute-acid hydrolysate of olive pomace supplemented with corn steep liquor	26.3 g/L using nanofiltration-detoxified olive pomace hydrolysate	Shows tolerance to salt and osmotic stress; suitable for conversion of complex hydrolysates	Further work should reduce nutrient supplementation costs and improve production intensity	[139]
Natural yeast/mixed-sugar substrate	Kluyveromyces marxianus ATCC 36907/CCA510	Fermentation of fruit-residue hydrolysates	Passion fruit peel hydrolysate and cashew apple bagasse hydrolysate	14.97 g/L using passion fruit peel hydrolysate; 17.04 g/L using cashew apple bagasse hydrolysate	Good temperature adaptability and potential for mixed-sugar utilization; suitable for xylitol production or xylitol/ethanol co-production	Glucose repression should be controlled; detoxification and concentration can improve xylose conversion efficiency	[140,141]
Natural yeast/high-titer process	Meyerozyma caribbica CP02/Pichia caribbica	Process optimization and activated-carbon detoxification; fermentation linked with crystalline product recovery	Optimized lignocellulosic hydrolysate system; detoxified hydrolysate with product recovery	124.1 ± 0.45 g/L; yield of 0.80 ± 0.02 g/g; 96.5% purity crystalline xylitol reported after recovery	Newly isolated or non-conventional yeast with strong xylitol-producing potential; links upstream fermentation with downstream crystallization	Can serve as a non-conventional yeast chassis for further screening, process optimization, and strain engineering	[117,142]
Natural yeast/detoxification-dependent process	Rhodotorula mucilaginosa	Overliming plus activated-carbon detoxification	Sugarcane bagasse pith hydrolysate	Yield of 0.496 g/g using detoxified hydrolysate	Detoxification strategy strongly affects xylitol production performance; the strain shows potential for tolerating complex substrates	Detoxification cost, pigment removal, and fermentation performance should be balanced	[143]
Natural yeast/immobilized fermentation	Barnettozyma populi NRRL Y-12728	Medium optimization and immobilization strategy	Xylose medium and immobilized fermentation system	31.2 g/L in optimized medium; 17.84 g/L in an immobilized system	Can limit arabitol by-product formation and is suitable for immobilized fermentation studies	By-product formation should be reduced, and adaptability to real hydrolysates should be improved	[116]
Natural yeast/staged oxygen control	Clavispora lusitaniae	Microaerobic fermentation and staged oxygen regulation	Saccharified sugarcane bagasse system	14.3 g/L under microaerobic conditions	Enables coordinated ethanol and xylitol production under different oxygen-supply stages; microaerobic conditions favor xylitol formation	Suitable for developing a single-reactor biorefinery mode with staged oxygen control	[144]
Engineered bacterium/fed-batch process	Recombinant E. coli	Engineered xylose reduction and cofactor regeneration; fed-batch cultivation	Hemicellulosic hydrolysate with co-substrate feeding; fed-batch reactor	172.4 g/L; approx. 2.2 mol xylitol/mol glucose co-substrate; 1.57 g/L/h	One of the highest reported microbial xylitol titers and productivities	Demonstrates the potential of bacterial chassis for high-productivity xylitol biomanufacturing, but co-substrate strategy and hydrolysate compatibility should be considered	[130]
Engineered yeast/industrial chassis	Industrial S. cerevisiae PE-2 GRE3	Overexpression of endogenous GRE3 xylose reductase; whole-slurry corncob hydrolysate strategy	High-xylose medium and lignocellulosic whole-slurry process	148.5 g/L; yield of 0.95 g/g	High-titer xylitol production in an industrial yeast background	Provides a robust and scalable yeast chassis, but xylose uptake and redox balance remain important engineering targets	[131]
Engineered bacterium/transporter engineering	Engineered E. coli with GlfL445I	XR screening, cofactor engineering, and xylose transporter engineering	Engineered E. coli shake-flask/bioprocess system	88.4 ± 0.7 g/L; yield of 0.95 g/g	Demonstrated the contribution of transporter engineering to xylose uptake and xylitol yield	Transporter engineering is important under high-xylose or mixed-sugar conditions	[132]
Engineered bacterium/non-detoxified hydrolysate	Genetically engineered E. coli mutant	Mutagenesis and strain engineering for non-detoxified hydrolysate utilization	Non-detoxified corncob hydrolysate; 15 L fed-batch bioreactor	82.0 g/L; 1.04 g/L/h	High titer and productivity from completely non-detoxified hydrolysate	Highlights the importance of inhibitor tolerance and robust chassis construction for reducing detoxification costs	[145]

integrates the representative microbial, process-optimized, and metabolically engineered xylitol production systems. The table highlights how different biological chassis and process strategies address distinct bottlenecks in xylitol biomanufacturing.

The integrated comparison in Table 3 demonstrates that natural yeasts, filamentous fungi, and engineered microbial systems contribute to xylitol production through distinct physiological characteristics and engineering strategies. Natural and non-conventional yeasts remain the most extensively investigated microbial hosts because they possess intrinsic xylose-reducing activity, efficient xylose assimilation pathways, and varying degrees of tolerance to lignocellulosic hydrolysates. These strains are especially relevant for processes using real biomass hydrolysates, where inhibitor tolerance, detoxification demand, mixed-sugar utilization, and oxygen-limited control strongly influence production performance. In addition to yeasts, several wild-type filamentous fungi belonging to the Zygomycetes, particularly T. elegans and M. isabellina, have also demonstrated promising xylitol-producing capabilities. T. elegans has been reported to produce approximately 31.1 g/L xylitol from commercial xylose [136], while M. isabellina achieved approximately 24.0 g/L xylitol under optimized cultivation conditions [137]. Although their xylitol titers are generally lower than those of the best-performing yeasts or engineered microorganisms, these fungi possess unique carbon partitioning characteristics and native xylose metabolism, making them attractive alternative microbial hosts for future metabolic engineering and biorefinery applications.

In contrast, engineered E. coli and S. cerevisiae systems can reach higher titers or productivities by redirecting intracellular carbon flux, strengthening xylose reduction, improving cofactor regeneration, and reducing competing pathways [102,127]. Engineered P. pastoris further broadens the production concept by enabling xylitol biosynthesis from non-xylose carbon sources, although its current titers are still lower than those of xylose-based systems [132]. Natural hydrolysate-tolerant yeasts are advantageous for direct biomass conversion, whereas naturally occurring filamentous fungi expand the diversity of native xylitol-producing microorganisms and provide additional microbial resources for future strain development. Engineered bacterial and yeast platforms generally exhibit superior titers and productivities under well-controlled fermentation conditions. Rather than being viewed as competing production systems, these microbial platforms should be considered complementary because each possesses distinct advantages in substrate utilization, inhibitor tolerance, metabolic characteristics, genetic accessibility, and industrial applicability. Therefore, future strain evaluation should not rely solely on final xylitol titer. A more systematic comparison should include titer, yield, volumetric productivity, substrate utilization efficiency, inhibitor tolerance, by-product formation, operational stability, reactor scalability, detoxification demand, and downstream recovery efficiency. For industrial implementation, the most promising systems will likely be those that combine the robustness of natural hydrolysate-tolerant yeasts and the metabolic diversity of naturally occurring filamentous fungi with the precision of metabolic engineering and the productivity advantages of intensified fermentation.

Separation, purification, and recovery of xylitol are among the most cost-sensitive steps in the biotechnological production route. Compared with chemical hydrogenation liquor, fermentation broth usually has a more complex composition. In addition to xylitol, it often contains residual sugars such as xylose, arabinose, and glucose; by-products such as arabitol, ethanol, and organic acids; and impurities including pigments, proteins, salts, and phenolic compounds. These components reduce crystallization selectivity and increase the burden of decolorization, desalting, membrane separation, chromatography, and evaporative concentration. Therefore, a single crystallization step is usually insufficient to obtain a high-purity xylitol product. In practical processes, an integrated downstream workflow is often required. This typically includes solid–liquid separation, decolorization, ion-exchange desalting, membrane separation or chromatographic refining, and concentration followed by crystallization. In recent years, new methods such as nanofiltration, reverse osmosis, supercritical carbon dioxide extraction, antisolvent crystallization, and process-coupled separation have shown potential. However, these technologies still require systematic evaluation in terms of recovery yield, selectivity, energy consumption, solvent recycling, membrane fouling, and continuous operation [19].

Overall, biotechnological production of xylitol is based on the high-value utilization of lignocellulosic resources and centers on the selective microbial reduction of xylose. It offers several advantages, including greener operation, mild reaction conditions, sustainability, and easy integration into biorefinery systems. However, this route still faces four key bottlenecks before stable industrial implementation can be achieved. First, pretreatment must balance xylose release, inhibitor formation, and process cost. Second, the composition of real hydrolysates often fluctuates, which requires production strains with stronger inhibitor tolerance and better adaptability to mixed sugars. Third, fermentation requires precise regulation of oxygen transfer, cofactor balance, and carbon flux distribution. Finally, downstream purification remains costly, and problems such as xylitol loss and co-crystallization with by-products have not yet been fully resolved.

Future research should shift from single-step optimization to full-process integration. At the feedstock stage, low-cost pretreatment strategies that generate fewer inhibitors should be developed. At the strain level, natural screening, adaptive laboratory evolution, metabolic engineering, and synthetic biology should be integrated to construct industrial chassis strains with high productivity, strong inhibitor tolerance, efficient xylose uptake, balanced cofactor supply, and low by-product formation. At the reaction-engineering stage, fed-batch fermentation, cell recycling, cell immobilization, staged oxygen control, and continuous fermentation should be further developed to improve volumetric productivity. At the downstream stage, highly selective, low-energy, and continuously operable separation technologies should be established by coupling membrane separation, adsorption, chromatography, and crystallization. Only when feedstock variability, strain performance, fermentation stability, downstream recovery, product purity, and life-cycle cost are evaluated together can biotechnological xylitol production move from laboratory feasibility to competitive industrial application.

3.3. Comparative Assessment, Industrial Scale-Up, and Downstream Processing

To provide a more comprehensive evaluation of the two xylitol production routes,

Table 4. Comparative assessment of chemical and biotechnological xylitol production from technical, economic, and environmental perspectives.

Evaluation Aspect	Chemical Synthesis	Biotechnological Production
Main conversion principle	Catalytic hydrogenation of xylose to xylitol [146]	Microbial or enzymatic reduction of xylose to xylitol [58]
Feedstock requirement	Usually requires purified or highly concentrated xylose solution [147]	Can use xylose-rich lignocellulosic hydrolysates, agricultural residues, or industrial by-products [148]
Representative best-reported TRY-related performance	Model-solution studies have reported very high catalytic performance, such as xylitol yield up to 98% over Co/SiO2 or Ni–Re/AC catalysts, approximately 80% xylitol yield from highly concentrated 76 wt.% xylose over Ni3Fe catalysts, and 96% xylose conversion with >99% xylitol selectivity over Cu–Ni/SiO2 catalysts [62,63,64,65,66]	Reported fermentation performance varies widely. High titers include 124.1 ± 0.45 g/L using Meyerozyma caribbica CP02 [104], 79.4 g/L using Pichia fermentans WC1507 [102], and 34.21 g/L using Candida tropicalis GS18 in detoxified rice straw hydrolysate [112]. Reported yields include 0.496 g/g using detoxified sugarcane bagasse pith hydrolysate [120].
Process maturity	Highly mature and widely used in industrial production [149]	Still developing; many studies remain at laboratory or pilot scale [19]
Catalyst or biocatalyst stability	Affected by metal leaching, sintering, support instability, poisoning by hydrolysate impurities, and incomplete recyclability [150]	Affected by strain robustness, genetic stability, inhibitor tolerance, oxygen-limited performance, repeated-batch stability, and by-product accumulation [151]
Energy consumption	High due to elevated temperature/pressure, H2 supply, xylose purification, concentration, and crystallization [149]	Lower reaction severity, but energy demand may arise from pretreatment, hydrolysate concentration, aeration, agitation, sterilization, and downstream purification [119]
Product purity	High-purity xylitol can be obtained after catalyst removal, decolorization, desalting, chromatography, concentration, and crystallization [146]	Recent integrated processes have reported crystalline xylitol purities of approximately 96.5–98% after purification and crystallization [104,106,119]
Scalability/TRL	Commercially established; current benchmark for large-scale xylitol production [152]	Promising but generally lower TRL; many studies remain at laboratory, bench, or pilot-oriented scale [153]
Operating conditions	Usually requires elevated temperature, high pressure, external hydrogen, and metal catalysts [154]	Usually proceeds under mild temperature and pressure conditions without high-pressure hydrogen [155]
Main advantages	Stable process control, high product consistency, established scale-up experience, and reliable commercial output [152]	Better sustainability potential, broader feedstock flexibility, and stronger connection with biomass valorization [153]
Main limitations	High energy demand, strict equipment requirements, catalyst cost, possible metal residues, and complex purification [150]	Hydrolysate inhibitors, limited strain robustness, oxygen-transfer control, cofactor imbalance, by-product formation, and costly downstream recovery [151]
Downstream processing	Requires catalyst removal, decolorization, desalting, concentration, separation, and crystallization [156]	Requires cell removal, decolorization, desalting, separation of residual sugars and by-products, concentration, and crystallization [157]
Environmental implication	Environmental pressure mainly comes from energy input, catalyst use, hydrogen supply, and wastewater treatment [146,149]	Potentially greener, but actual environmental benefit depends on pretreatment, detoxification, fermentation efficiency, and recovery process [148,153]
Techno-economic and life-cycle evidence	Chemical synthesis is commercially established, but systematic public TEA/LCA data are less frequently reported because industrial operation data are often proprietary. Environmental burdens are mainly associated with xylose purification, hydrogenation, energy input, catalyst use, and wastewater treatment [146,149]	Recent TEA/LCA studies on lignocellulosic xylitol biorefineries indicate commercial potential but also identify pretreatment, fermentation, downstream recovery, energy input, and co-product allocation as key determinants of cost and environmental performance [158]. For example, sugarcane bagasse-based biorefinery analysis reported a product cost of approximately 230 INR/kg xylitol and cradle-to-gate greenhouse gas emissions of 2.759 kg CO2-eq/kg xylitol [159].
Industrial position	Current industrial benchmark for large-scale xylitol production [14,152]	Promising green manufacturing strategy, but not yet a full replacement for the chemical route [160]
Future improvement focus	Lower reaction severity, improve catalyst stability, reduce energy consumption, and simplify purification [146,149,152]	Improve strain performance, inhibitor tolerance, fermentation intensity, product selectivity, and downstream recovery efficiency [147,151]

compares chemical synthesis and biotechnological production in terms of process maturity, feedstock adaptability, industrial feasibility, and sustainability potential. In response to the need for a more quantitative comparison, the table further summarizes representative best-reported TRY-related indicators, including titer or concentration, reaction rate or productivity where available, and yield or selectivity. Because chemical hydrogenation and microbial fermentation use different reporting conventions, xylose conversion and xylitol selectivity or yield are emphasized for the chemical route, whereas xylitol titer, yield, and volumetric productivity are emphasized for the biotechnological route.

From the perspective of industrial-scale production, chemical synthesis remains the dominant commercial route because it relies on established unit operations, including xylose purification, catalytic hydrogenation, catalyst removal, decolorization, desalting, concentration, chromatographic separation, and crystallization. Its technology readiness level is therefore high, and the process already has a strong basis for continuous or semi-continuous industrial operation [58,161]. In contrast, biotechnological xylitol production has shown considerable promise in laboratory, bench-scale, and pilot-oriented studies, but its overall technology readiness remains lower [19]. Most reported processes have been validated in shake flasks, stirred-tank bioreactors, airlift reactors, immobilized-cell systems, or small-scale fed-batch configurations, whereas integrated pilot-scale demonstrations using real lignocellulosic hydrolysates and complete downstream recovery remain limited [118].

Bioreactor configuration is a key factor in the scale-up of biotechnological xylitol production. Stirred-tank bioreactors allow for precise control of pH, temperature, agitation, aeration, and the volumetric oxygen transfer coefficient, making them suitable for studying process kinetics and oxygen-limited xylitol accumulation [60]. Airlift reactors can reduce mechanical shear and energy input, and may be advantageous for immobilized-cell or repeated-batch systems. Immobilized-cell reactors support cell reuse and can improve operational stability, but mass-transfer limitation and carrier cost must be carefully controlled [58]. Fed-batch operation is also attractive because it can maintain xylose availability, reduce substrate inhibition, and improve volumetric productivity. However, scale-up remains challenging because oxygen transfer, mixing efficiency, heat removal, foam formation, hydrolysate variability, contamination control, and downstream impurity load may change substantially when moving from laboratory to industrial systems [19].

Recent techno-economic analysis and life-cycle assessment studies suggests that biotechnological xylitol production can be economically and environmentally attractive when low-cost lignocellulosic feedstocks, efficient fermentation, high product recovery, and co-product valorization are achieved [159]. Life-cycle studies of integrated xylitol biorefineries further show that process configuration, energy supply, pretreatment severity, wastewater treatment, and co-product allocation strongly influence the final environmental profile [162]. Therefore, the environmental superiority of the biotechnological route should not be assumed solely from mild reaction conditions; it must be demonstrated through integrated TRY performance, product recovery, and TEA/LCA indicators [163].

Commercialization of the biotechnological route depends not only on fermentation performance, but also on the efficiency of downstream purification and crystallization. Compared with chemical hydrogenation liquor, fermentation broth usually contains cells, residual xylose, arabinose, glucose, arabitol, ethanol, organic acids, proteins, pigments, salts, and phenolic compounds [164]. These impurities decrease crystallization selectivity and increase the cost of decolorization, desalting, membrane filtration, electrodeionization, chromatography, evaporation, and crystallization [165]. Therefore, downstream processing should be evaluated using recovery yield, crystallization yield, product purity, energy consumption, resin or adsorbent regeneration, wastewater generation, and compatibility with continuous operation. Representative recent purification and crystallization strategies are summarized in

Table 5. Recent purification and crystallization strategies for xylitol recovery.

Downstream Strategy	Main Process Features	Reported Purity or Recovery Performance	Advantages	Main Limitations	Industrial Relevance
Activated carbon detoxification followed by concentration and crystallization	Activated carbon treatment for inhibitor removal, fermentation of concentrated hydrolysate, and crystallization of xylitol	Pichia caribbica produced 124.1 ± 0.45 g/L xylitol with a yield of 0.80 ± 0.02 g/g; crystallized xylitol reached 96.5% purity [142]	Provides an end-to-end bioprocess from corncob hydrolysate to crystalline xylitol; relatively high titer and product purity	Requires effective hydrolysate detoxification and concentration; crystallization performance depends on broth impurity profile	Relevant to biorefinery-based scale-up because it links upstream fermentation with crystalline product recovery
Membrane-based filtration followed by crystallization	Membrane-based filtration combined with crystallization after fermentation using a non-conventional aeration strategy	Xylitol yield of 0.86 ± 0.015 g/g and productivity of 0.74 g L−1 h−1; crystals showed approximately 98% purity; 0.584 kg food-grade xylitol crystals were obtained from 3.5 kg corncob biomass [166]	High product purity; reduced agitation energy; provides material balance and toxicity evaluation	Membrane cost, fouling, process control, and scalability still require further validation	Promising for food-grade xylitol production and process-intensified recovery
Ultrafiltration combined with electrodeionization	Ultrafiltration removes macromolecular impurities, followed by electrodeionization to reduce ionic impurities	UF–EDI was reported to remove most impurities from microbial xylitol broth; higher current density improved impurity removal [167]	Lower thermal burden than evaporation-intensive purification; useful for desalting and impurity reduction	Crystal purity and crystallization yield are not always directly reported; membrane fouling and electricity consumption need evaluation	Useful as a polishing or pre-crystallization purification step
Antisolvent-assisted crystallization of biotechnological xylitol	Fermentation broth concentration followed by antisolvent-assisted crystallization using ethanol, isopropanol, or protic ionic liquid systems	In cashew apple bagasse hydrolysate-derived broth, the best condition used 50% isopropanol and a 0.5 °C/min cooling rate, producing crystals with 84.8% purity and 69.7% crystallization yield [168]	Can enhance crystallization from complex fermentation broths; provides an alternative to direct cooling crystallization	Residual sugars may inhibit crystallization; solvent recovery, safety, and cost must be considered	Suitable for complex hydrolysate-derived broths, but solvent recycling is essential for scale-up
Cooling, evaporative, and antisolvent crystallization	Batch crystallization by cooling, evaporation, antisolvent addition, or combined antisolvent–cooling strategies	Recent comparative crystallization studies show that nucleation, viscosity, solvent composition, and supersaturation strongly affect crystal formation and recovery [169]	Provides systematic comparison of crystallization modes; useful for optimizing crystal size and process design	Performance depends strongly on solution composition; model systems may not fully represent fermentation broth	Important for designing robust final crystallization steps
Crystallization from agro-industrial hydrolysate fermentation broth	Fermentation of de-oiled rice bran hydrolysate followed by concentration and crystallization	Candida guilliermondii NCIM 3044 produced 64.37 g/L xylitol with a yield of 0.59 g/g xylose; the product was concentrated to 148.2 g/L and crystallized [170]	Demonstrates the use of agro-industrial residues for crystalline xylitol production	Final crystal purity and recovery yield require more detailed reporting and optimization	Supports expansion of xylitol production from low-cost agricultural by-products
Crystallization-focused process evaluation and techno-economic perspective	Evaluation of physicochemical factors, crystallization behavior, and process economics for bioprocessed xylitol	Recent reviews emphasize that crystallization can produce high-purity xylitol, but recovery efficiency depends on broth composition, supersaturation, nucleation, impurity removal, and process cost [171]	Provides process-level guidance and techno-economic perspective	Requires validation using real fermentation broths and integrated pilot-scale operation	Useful for identifying industrial bottlenecks and future process design criteria

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4. Application Fields of Xylitol

Xylitol is a polyol sweetener with a sweetness close to that of sucrose, but with lower caloric value and a lower glycemic index. Its absorption and metabolism in the body are mainly associated with the liver and gut microbiota, and do not depend on insulin. Because xylitol is absorbed relatively slowly in the intestine, the D-glucose generated during its metabolism can first be stored in the liver as glycogen and then released gradually. As a result, xylitol is less likely than sucrose or glucose to cause rapid postprandial fluctuations in blood glucose. It is therefore considered a suitable alternative sweetener for individuals with diabetes [29]. According to current regulatory information from the U.S. FDA, xylitol is permitted for use in food systems as a sugar alcohol sweetener, provided that its use level does not exceed the amount required to achieve the intended technical effect [172,173].

4.1. Applications in the Food Sector

In the food industry, xylitol is mainly used as a functional sweetener to replace sucrose. Because it has a sweetness close to that of sucrose, a cooling mouthfeel, and lower caloric and glycemic effects, xylitol has been widely incorporated into the formulation of sugar-free confectionery, chewing gum, low-sugar baked products, functional beverages, and diabetes-friendly foods [14,20,174]. Beyond sweetness, xylitol can also improve food quality by regulating moisture retention, texture formation, and flavor release.

For example, in confectionery and gel-based foods, partial or complete replacement of sucrose with xylitol can reduce sugar load while maintaining good mouthfeel, flexibility, and sensory acceptance. This provides a feasible strategy for developing low-sugar and functional confectionery products [175]. In dysphagia-oriented foods and protein gel systems, xylitol can also participate in gel-structure regulation and sweetness release. It may therefore provide a theoretical basis for texture optimization in foods for special medical purposes and nutritional products for older adults [176].

In baked products, xylitol can be used in sugar-reduced formulations for bread, muffins, biscuits, and cakes. It helps reduce sucrose addition and product energy density, while improving the nutritional profile of these products [177]. However, the role of xylitol in baked systems is not limited to sweetness replacement. Its dosage, molecular structure, and interactions with starch, gluten proteins, and water can strongly affect dough rheology, fermentation performance, specific volume, texture, and sensory quality. Studies have shown that an appropriate level of xylitol can improve crust color and crumb fineness. However, excessive addition may weaken the formation and stability of the gluten network [178]. In addition, yeast cannot efficiently use xylitol as a fermentable substrate. A high replacement level may therefore reduce gas production during fermentation and limit oven spring. This can lead to reduced loaf volume, a denser internal structure, and poorer textural quality.

On the other hand, sugar alcohol molecules can form hydrogen bonds with starch chains through their hydroxyl groups. This affects starch gelatinization, gel formation, retrogradation, and water migration and redistribution. These processes are closely related to staling in baked products. Therefore, the moderate incorporation of xylitol may help delay starch retrogradation, improve mouthfeel during storage, and extend shelf life [179]. It should be noted that xylitol is often described in earlier literature as “not undergoing the Maillard reaction.” Recent studies suggest a more nuanced view. In complex food matrices and during long-term storage, xylitol-containing products may still show reaction features related to browning and fluorescent product formation. A more rigorous statement is therefore that xylitol, as a polyol, does not show the same browning behavior as reducing sugars or sucrose under typical thermal-processing conditions. However, its thermal and storage stability in real food systems should still be evaluated in relation to matrix composition, water activity, temperature, and storage time [180].

From a nutritional and health perspective, long-term excessive intake of refined sugar is closely associated with an increased risk of chronic diseases, including obesity, diabetes, dental caries, cardiovascular disease, and metabolic syndrome. Partial replacement of sucrose with xylitol can reduce dietary sugar load and postprandial glycemic response to some extent. It may also have positive implications for body weight management and metabolic health [20,181]. Human trials have shown that, compared with sucrose preload, xylitol preload may reduce total energy intake during subsequent ad libitum eating. This suggests that xylitol has potential value in the design of low-energy diets and glycemic-control foods [38]. However, the health effects of xylitol and other sugar alcohol sweeteners should not be attributed simply to their “low-calorie” nature. Their practical value is also shaped by several factors, including intake dose, gastrointestinal tolerance, individual metabolic status, long-term exposure risk, processing compatibility, and consumer acceptance [9,47].

Therefore, in food formulation development, xylitol should be positioned as a functional sweetening component in sugar-reduction systems, rather than as a “healthy sugar” that can be consumed without limitation. Future studies should further investigate the interaction mechanisms between xylitol and proteins, starch, dietary fibers, hydrocolloids, and blended sweetener systems. A better understanding of these interactions will help achieve coordinated optimization of sweetness quality, texture stability, processing adaptability, nutritional and health attributes, and cost control.

4.2. Applications in Oral Care and Dental Caries Prevention

Among the health-related applications of xylitol, oral health is one of the most extensively studied areas with relatively strong evidence. Xylitol is a sugar alcohol that is not readily fermented into acids by cariogenic bacteria such as S. mutans. It may reduce the risk of dental caries by inhibiting bacterial adhesion, reducing dental plaque biofilm formation, promoting salivary secretion and acid clearance, and, to some extent, supporting enamel remineralization [181,182,183]. Based on these effects, xylitol has been widely used in sugar-free chewing gum, lozenges, confectionery, syrups, toothpaste, mouthwash, and oral sprays [12,13,184,185].

Most existing clinical studies have focused on caries prevention in children. The available evidence suggests that repeated daily exposure to xylitol, with a total intake of approximately 5–6 g per day, may provide favorable anticaries effects. For young children, local delivery forms such as xylitol syrup, lozenges, and wipes have also shown a certain degree of safety and feasibility during the eruption of primary teeth [186]. Recent studies support a positive role of xylitol chewing gum in reducing dental plaque or lowering cariogenic bacterial levels. However, large differences remain among studies in product type, dose, frequency of use, follow-up duration, and baseline caries risk of participants. As a result, the strength of evidence is still somewhat inconsistent [187,188,189,190].

In recent years, research on xylitol-based oral care products has expanded from caries prevention alone to oral microbiota modulation and formulation synergy. Studies have examined not only the effects of xylitol chewing gum on salivary pH, plaque index, and S. mutans levels, but also its antibacterial potential when combined with licorice, essential oils, surfactants, and other active ingredients [191,192]. For example, chewing gum containing both xylitol and licorice has shown formulation value in terms of anticaries activity and pharmacokinetic behavior [193]. Oral microbiome studies also suggest that xylitol may contribute to oral microbial homeostasis by limiting the metabolic activity of cariogenic bacteria [194,195].

In addition, xylitol-containing mouthwash can inhibit the growth of Streptococcus sanguinis and S. mutans at an early stage. Fluoride toothpaste containing 10% xylitol has also shown a greater caries-reducing effect than fluoride toothpaste alone, suggesting a possible synergy between xylitol and fluoride [196]. Overall, xylitol has practical value in lowering cariogenic bacterial levels, reducing plaque formation, and supporting caries prevention. However, its real-world effectiveness is still influenced by dose, exposure frequency, user compliance, formulation-release properties, and the baseline caries risk of the target population [197]. Therefore, xylitol should be regarded as an adjunctive oral health intervention alongside fluoride use, mechanical cleaning, and dietary sugar control, rather than as a replacement for conventional caries-prevention measures.

4.3. Applications in Pharmaceutical and Health-Related Fields

Beyond its use as a sweetener and functional ingredient in oral care, xylitol research has gradually expanded to several health-related fields. These include gut microbiota modulation; ear, nose, throat and respiratory care; metabolic health; anti-inflammatory and anti-infective applications; and bone health. In terms of gut health, xylitol is a poorly digestible and slowly absorbed sugar alcohol. A fraction of ingested xylitol can reach the colon and be utilized by intestinal microorganisms. In vitro dynamic colon models and animal studies have shown that xylitol and its derived oligosaccharides can affect the production of short-chain fatty acids, promote the formation of propionate or butyrate, and may modulate the abundance of beneficial bacteria such as Bifidobacterium and Lactobacillus [43]. These findings provide experimental support for the use of xylitol in gut microbiota regulation and functional food development [198,199,200,201]. However, the intestinal effects of xylitol are clearly dose-dependent. Excessive intake is associated with gastrointestinal symptoms such as bloating and diarrhea. Therefore, the practical use of xylitol as a prebiotic-like functional component still requires further validation through human clinical studies.

In ear, nose, throat, and respiratory care, xylitol exerts its effects by reducing the salt concentration of airway surface liquid, enhancing local innate antibacterial defense, and inhibiting pathogen adhesion. Previous studies have shown that xylitol can reduce the number of coagulase-negative staphylococci in the nasal cavity. It also shows inhibitory effects against the Burkholderia cepacia complex, biofilms associated with chronic rhinosinusitis, and human respiratory syncytial virus [202,203]. Xylitol nasal sprays or irrigation solutions have also been explored for their potential to improve the nasal microenvironment, reduce bacterial adhesion, and support disease management [204]. Clinical studies suggest that xylitol has a certain degree of safety and feasibility in the prevention of recurrent acute otitis media in children, postoperative care after functional endoscopic sinus surgery, and outpatient adjunctive treatment of COVID-19 infection [42,205]. For the prevention and management of acute otitis media, xylitol can reduce the adhesion of pathogens such as Streptococcus pneumoniae and Haemophilus influenzae to nasopharyngeal epithelial cells. This effect is associated with changes in bacterial surface structures or the blocking of bacterial lectins [206]. Other studies have reported that daily intake of 2–5 g xylitol oral solution is associated with a lower incidence of acute otitis media. However, no unified global guideline for this application has yet been established [207]. In addition, nebulized inhalation of 15% xylitol solution, 5 mL twice daily for two weeks, has been reported to be safe and feasible in hospitalized patients with cystic fibrosis [208].

In systemic health-related fields, xylitol has also shown research value. As a low-calorie sweetener, xylitol may contribute to body weight management by enhancing satiety [22]. In addition, given the prebiotic-like properties of sugar alcohols, xylitol is also considered to be involved in gut microbiota modulation [209]. In oxidative stress-related conditions, xylitol dehydrogenase, which participates in xylitol metabolism, can promote NADH generation and may help attenuate oxidative damage. Therefore, xylitol has been proposed to have potential intervention value in hemolytic anemia associated with glucose-6-phosphate dehydrogenase deficiency [31]. In anti-inflammatory and anticancer studies, xylitol has been reported to inhibit the adhesion of Porphyromonas gingivalis and the release of inflammation-related mediators induced by this pathogen. It has also shown inhibitory effects on the proliferation of several tumor cell lines in vitro [210]. In addition, xylitol may alleviate hyperosmotic stress responses in keratinocytes by regulating IL-1α expression and Ca²⁺ signaling [211]. In lipid metabolism, xylitol is involved in metabolic regulation through its effects on the expression of carbohydrate response element-binding protein, lipogenic enzymes, fatty acid oxidation-related genes, and sterol regulatory element-binding protein 1c. It may also enhance the tolerance of multiple organs to diabetes-related oxidative stress [48,212]. Xylitol may promote bone healing and increase bone mineral density-related indicators in an animal bone-defect model [213].

It should be noted that, with increasing xylitol intake and expanding application scenarios, greater attention is being paid to its long-term safety. Recent studies have reported an association between elevated circulating xylitol levels and an increased risk of major adverse cardiovascular events, together with enhanced platelet responsiveness and thrombosis potential in experimental and short-term intervention settings [214]. However, these findings should not be interpreted as establishing a causal relationship between habitual dietary xylitol intake and cardiovascular disease. Subsequent analyses have emphasized that circulating xylitol may partly reflect endogenous metabolism, that observational associations cannot establish causality, and that the available platelet-response data are based on limited short-term studies [215]. Therefore, further well-controlled and adequately powered human intervention studies are required before firm conclusions can be drawn regarding the long-term cardiovascular safety of dietary xylitol. Accordingly, currently available evidence does not negate the appropriate use of xylitol in foods, oral-care products, and related health products, but supports continued risk–benefit evaluation, particularly under long-term or high-dose exposure conditions and in populations with elevated baseline cardiovascular risk.

Overall, the functional role of xylitol has gradually expanded from that of a conventional low-calorie sweetener to a functional ingredient with antibacterial activity, microbiota-modulating effects, metabolic regulatory potential, and possible systemic health benefits. However, except for areas such as oral health, where the evidence base is relatively well established, other application fields still require more high-quality human studies. Future research should further clarify the effective dose, target populations, mechanisms of action, and long-term safety of xylitol.

4.4. Applications in Other Fields

Xylitol contains multiple hydroxyl groups in its molecular structure. This gives it good hydrophilicity, humectant capacity, osmotic regulation ability, and chemical modifiability. Therefore, xylitol can be used not only as a conventional humectant and auxiliary sweetening ingredient, but also as a polyol platform molecule in personal care formulations, surfactants, plasticizers, functional materials, and the modification of medical materials [17,216].

In personal care products, xylitol and its derivatives are used as humectants, skin-conditioning agents, oral-care actives, and antibacterial formulation components. Studies on skin hydration, transepidermal water loss, and skin-barrier-related gene expression indicate that xylitol improves skin moisture retention and supports barrier function [217,218]. Xylitol also shows concentration-dependent effects on skin-related microorganisms, including Staphylococcus aureus, Staphylococcus epidermidis, and Cutibacterium acnes: low concentrations may support certain commensal bacteria, whereas higher concentrations can inhibit selected skin pathogens [216]. These results provide preliminary support for its use as a moisturizing and microbiota-modulating ingredient in personal care formulations, but its effective concentration range, formulation stability, and long-term safety still need to be clarified.

Moreover, a combined active system composed of propylene glycol, caprylic acid, and xylitol has shown antibacterial and skin-care potential in in vitro and in vivo acne-related studies. This further expands the application scenarios of xylitol and its derivatives in personal care formulations [219].

Beyond its moisturizing and antibacterial effects, xylitol has attracted increasing attention for its potential role in skin barrier repair and wound care. Human skin studies have shown that continuous use of a topical formulation containing 5% xylitol and 5% glycerol can increase hydration in dry skin, reduce transepidermal water loss, and enhance filaggrin expression. These findings provide experimental support for the involvement of xylitol in improving skin barrier function [217].

In normal human epidermal keratinocytes, xylitol can upregulate the expression of genes related to keratinization, tight junctions, and barrier homeostasis, including filaggrin, keratin, involucrin, and occludin. This effect is linked to activation of the MAPK pathway and protein kinase Cδ, thereby contributing to the regulation of epidermal differentiation [220]. Further studies have shown that xylitol-containing topical formulations can increase skin water content, reduce water loss, and show barrier-protective and anti-irritant effects in dry skin or irritant dermatitis models [211,221]. Long-term dietary xylitol supplementation has also been reported to affect skin collagen metabolism, increase acid-soluble collagen content, and reduce fluorescence intensity associated with collagen glycation. These findings suggest that xylitol may have a regulatory role in skin aging and diabetes-related collagen abnormalities [222].

In wound care, xylitol can inhibit the growth of chronic wound-associated pathogens, including Pseudomonas aeruginosa, S. aureus, and Enterococcus faecalis. At relatively high concentrations, xylitol has been reported to completely suppress biofilm formation. When combined with components such as lactoferrin, its inhibitory effect against biofilms formed by P. aeruginosa and methicillin-resistant S. aureus is further enhanced [223]. In addition, an emollient formulation containing xylitol and farnesol has been shown to reduce S. aureus counts and improve skin hydration in volunteers with atopic dermatitis. These findings suggest that xylitol has potential as an adjunctive care ingredient for inflammatory skin diseases [224].

In materials chemistry and tissue engineering, xylitol can be functionalized through esterification, phosphorylation, or interactions with polymer matrices. In recent years, increasing attention has been given to the construction of functional materials using xylitol as a structural unit or modifier. Xylitol-containing polyester materials can be designed with different mechanical properties and physicochemical features by adjusting the type of dicarboxylic acid, carbon-chain length, and crosslinking conditions. This provides a new structural building block for the design of degradable and biocompatible medical materials [225].

For example, xylitol-modified electrospun polymer scaffolds can improve the physicochemical properties and antibacterial performance of materials, offering a new strategy for developing tissue-engineering scaffolds and functional wound dressings [226]. Poly(xylitol dodecanedioate), a xylitol-based polymer, can be used as a carrier for fibroblast growth factor. This system improves release behavior and promotes the adhesion and proliferation of human fibroblasts, showing potential in tissue repair and regenerative medicine [227]. Because xylitol fatty acid monoesters can construct stable oleogels and serve as delivery carriers for β-carotene, they show potential application value in food colloids and lipid-replacement systems [228]. Xylitol-based environmentally friendly plasticizers have also been used to modify polymer systems such as polylactic acid/poly(butylene succinate), helping improve the flexibility and processing performance of bio-based materials [229]. In flame-retardant and fiber materials, xylitol can work together with green components such as phytic acid to modify bacterial cellulose. This approach can improve both flame retardancy and flexibility, providing a new design strategy for green flame-retardant textiles and bio-based functional materials [230].

In summary, xylitol has evolved from a conventional humectant and auxiliary sweetening ingredient into a reactive polyol platform molecule with expanding applications in personal care and materials science. It now combines multiple functions, including moisturization, antibacterial activity, barrier repair, antibiofilm effects, collagen metabolism regulation, green plasticization, and functional material construction. Compared with more mature application fields such as food and oral care, research on xylitol in personal care materials, medical materials, and functional polymers is still developing rapidly. To achieve higher-level industrial application, future studies should systematically address key issues such as raw material cost, reaction selectivity, product stability, formulation compatibility, toxicological safety, and scalable production processes.

5. Conclusions and Perspectives

Xylitol is a five-carbon sugar alcohol with favorable sweetness characteristics and multiple physiological functions. Because of its sucrose-like sweetness, lower caloric value, mild glycemic response, and low cariogenicity, xylitol has established a solid application basis in sugar-free foods, oral care, special dietary products, pharmaceutical nutrition, and personal care products. Current studies show that xylitol not only meets the need for sweetness replacement in low-sugar and sugar-free foods, but also supports oral health by reducing acid production by cariogenic bacteria and inhibiting dental plaque accumulation. At the same time, xylitol shows further potential in gut microbiota modulation, nutritional health products, pharmaceutical excipients, humectants, and the development of bio-based chemicals.

Xylitol is present only at limited levels in natural plants and foods, making direct extraction unsuitable for industrial production. Large-scale production still relies mainly on catalytic hydrogenation of xylose. This route is mature, efficient, and supported by extensive scale-up experience. Yet its high-temperature and high-pressure conditions, high energy demand, dependence on metal catalysts, environmental burden, and separation and purification costs limit further green upgrading. By contrast, biotechnological routes based on lignocellulosic hydrolysates, agricultural wastes, and other renewable resources provide a more sustainable direction for green xylitol manufacturing.

Future research needs to focus on two main directions: production processes and application evaluation. In terms of production, improving the utilization efficiency of low-cost feedstocks, optimizing pretreatment and detoxification processes, and developing production strains with higher tolerance and productivity remain important priorities. At the same time, xylose transport, cofactor balance, metabolic flux regulation, and the coordination between continuous fermentation and separation processes directly affect xylitol yield and production stability. Since downstream crystallization and purification remain costly, future studies should also focus on more efficient, low-energy, and scalable separation and purification methods.

In terms of application, as xylitol is used in a wider range of products, its functional effects and safety require more thorough validation. Product form, intake dose, frequency of use, and differences among target populations can all influence its practical effects and tolerance. In particular, gastrointestinal discomfort and potential metabolic risks under long-term or relatively high-dose intake conditions deserve further attention.

In summary, xylitol already has a relatively well-established application basis as a functional sweetener and an oral-health-related ingredient. Its applications in pharmaceuticals, personal care, and bio-based materials are still being further explored. In the future, the value of xylitol should not be limited to sucrose replacement. It can also be further developed as a functional polyol and bio-based feedstock with broader potential. However, these wider applications still need support from experimental studies, clinical evaluation, life-cycle assessment, and techno-economic analysis.