Postbiotics Derived from Lactic Acid Bacteria Fermentation: Therapeutic Potential in the Treatment of Muscular Complications in Inflammatory Bowel Disease

Abstract

Inflammatory bowel disease (IBD) is characterized by chronic inflammation in the gastrointestinal tract, which can result in several muscular complications, including sarcopenia, the loss of muscle mass, and impaired muscle function. Recently, postbiotics derived from lactic bacteria, such as Lactobacillus and Bifidobacterium, have emerged as potential therapeutic modulators for these complications. Postbiotics are bioactive metabolites, such as short-chain fatty acids (SCFAs), antimicrobial peptides, and other compounds produced by microorganisms during fermentation, which have anti-inflammatory, antioxidant, and metabolic regulatory effects. These metabolites are important due to their potential to positively influence muscle health in patients with IBD, mainly by reducing systemic and local inflammation, improving gut microbiota, and modulating muscle metabolism. Studies suggest that these postbiotics may help minimize muscle degradation and promote muscle tissue regeneration, assisting in the prevention or management of IBD-associated sarcopenia. Despite the promising results, challenges remain, such as variability in postbiotic production and the need for further clinical studies to establish clear therapeutic guidelines. This review article explores the mechanisms of action of postbiotics derived from lactic acid bacteria and their potential applications in the treatment of muscle complications in patients with IBD, highlighting future therapeutic perspectives.

1. Introduction

Inflammatory bowel disease (IBD) is a chronic, progressive, immune-mediated condition characterized by the dysregulation of both innate and adaptive immune responses. The most well-known forms of IBD are Crohn’s disease and ulcerative colitis, whose etiologies are complex and involve a combination of genetic, microbial, and environmental factors [1,2]. IBD is thought to arise as a response to an initial insult to the epithelial barrier in specific intestinal regions, which may be influenced by factors such as diet-induced dysbiosis, exposure to chemical compounds, or infectious agents [3].

In recent years, the prevalence of IBD has increased significantly worldwide [4]. For example, a retrospective study evaluating 226 patients found that approximately 54 were diagnosed with IBD, including 44 cases of ulcerative colitis (19.46%) and 10 cases of Crohn’s disease (4.42%), affecting individuals across different age groups and both sexes [5]. Clinically, IBD can lead to various muscular complications due to associated metabolic disorders and nutritional deficiencies, which negatively impact muscle function [4]. It has been reported that more than one-third of adult IBD patients present with myopenia and pre-sarcopenia [6], conditions linked to poor nutrient absorption, which is primarily caused by the inflammatory process. This inflammation reduces the contact time between the intestinal mucosa and nutrients, impairing the absorption of essential compounds such as aminoacids [4,7].

The incidence of sarcopenia in IBD patients is estimated to be as high as 60%, accompanied by reduced muscle strength [8]. This decline is not only due to the diminished bioavailability of nutrients but also the inflammatory milieu inherent to IBD. Elevated levels of pro-inflammatory cytokines inhibit protein synthesis and promote the generation of reactive oxygen species, further contributing to muscle dysfunction [8]. Therapeutic approaches to IBD commonly include the use of corticosteroids, immunosuppressants, 5-aminosalicylic acid (5-ASA), biological agents, and dietary management [9]. Notably, the intestinal microbiota plays a critical role in these treatments, as scientific evidence supports the benefits of selected probiotic strains in preventing and managing ulcerative colitis and Crohn’s disease [10].

The intestinal microbiota consists of over 1000 bacterial species and other microorganisms, whose imbalance is linked to various metabolic diseases. Consequently, preserving and restoring the gut microbiome has become a significant focus, with functional dietary components such as prebiotics, probiotics, and postbiotics gaining prominence [11]. Prebiotics are non-digestible fibers that selectively promote the growth and activity of beneficial intestinal bacteria like Lactobacillus, Bifidobacterium, and Bacteroides [10]. Probiotics are live microorganisms that maintain intestinal homeostasis, modulate the immune system, and support physiological functions. Postbiotics, as defined by the International Scientific Association for Probiotics and Prebiotics (ISAPP), are preparations of inactivated microorganisms and/or their components that confer health benefits to the host. These bioactive substances result from interactions between probiotics and prebiotics through fermentation [12].

Postbiotics offer several advantages over probiotics, including longer shelf life, easier storage and transportation, and no risk of transferring antibiotic resistance genes or virulence factors. This enhances their safety profile, especially for immunocompromised individuals [12]. Moreover, postbiotics are more stable against processing, storage, and gastrointestinal conditions, making them a promising therapeutic alternative [12]. Lactic acid bacteria (LAB), such as Lactobacillus and Bifidobacterium, are primary producers of postbiotics. These bacteria are extensively used industrially in fermentation processes to obtain postbiotic by-products, including organic acids, peptides, and exopolysaccharides (EPSs) [13].

Given their anti-inflammatory properties and role in restoring microbial balance, postbiotics have therapeutic potential in IBD management [14]. However, challenges remain in their clinical application, such as variability in postbiotic production and the need for further research to confirm their therapeutic efficacy. This review aims to discuss the mechanisms of action of postbiotics and explore their application in treating muscular complications associated with IBD.

2. Postbiotic: Mechanisms of Action and Benefits

Postbiotics are bioactive compounds generated by microorganisms during fermentation processes, which may include non-viable whole cells, cell fragments, metabolites, or other released substances. These components exert beneficial effects on the host’s health, similar to probiotics, but without the need for the microorganisms to be alive. Thus, postbiotics offer benefits such as greater safety and stability, reducing risks associated with the consumption of viable microorganisms [14,15,16,17].

Postbiotics have been considered as a therapeutic intervention for various pathologies, such as kidney diseases (hyperoxaluria), oncological diseases (colorectal cancer), metabolic disorders (diabetes), inflammatory diseases (rheumatoid arthritis and IBD), and even neurodegenerative diseases [18,19,20,21,22].

Some studies highlight the benefits of postbiotics. In the study by Du et al. (2022) [23], the action of postbiotics derived from the strains Lacticasebacillus rhamnosus, Limosilactobacillus reuteri and Bifidobacterium animalis on silica-induced cytotoxicity and inflammation in an in vitro macrophage model was investigated. The results demonstrated the compounds’ anti-inflammatory activity, in addition to a significant reduction in toxicity. Wang et al. (2024) [24] also noted a reduction in inflammation in addition to the proliferation and differentiation of intestinal stem cells in mice after the use of postbiotics. Di Chiano et al. (2024) [25] observed that postbiotics were able to act at the brain level, protecting and preventing microglial cells from experiencing oxidative stress.

However, the benefits of postbiotics are directly related to the fermentation process. Fermentation by LAB, such as Lactobacillus and Bifidobacterium, is widely used for the synthesis of postbiotics due to their ability to produce a variety of bioactive compounds that are beneficial to human health. These bacteria, which are commonly found in fermented foods such as yogurt and kefir, play a crucial role in the production of organic acids, peptides, and other substances that can have antimicrobial, anti-inflammatory, and immunomodulatory effect [17,26]. During the fermentation process, these bacteria metabolize nutrients in the substrate, releasing cell fragments and metabolites that, even after the death of microorganisms, continue to provide health benefits to the hosts [17,26].

In addition to the widely studied genera mentioned above, other genera of microorganisms have shown potential for use in the production of postbiotics through the fermentation process, such as some species of the genera Fructilactobacillus, Enterococcus, Akkermansiamuciniphila, Eubacateriumhallii, and Streptococcus, found in various foods [13,27,28]. These strains display distinct metabolic behaviors and result in a variety of bioactive compounds beneficial to human health. Streptococcus thermophilus has been explored as a rich postbiotic source due to its applications in the food industry. It is associated with yogurt starter cultures as it is a bacterial strain considered ‘Generally Recognized as Safe’ (GRAS), converting lactose into lactic acid during fermentation, and an EPS producer, a status characterizing its anti-inflammatory and immunomodulatory properties, even after undergoing hydrolysis [29,30].

Other genera such as Lacticaseibacillus and Pediococcus are also of great relevance for the production of postbiotics. Studies have demonstrated the health properties of the postbiotics produced using strains of Lacticaseibacillus paracasei due to the immunomodulatory effects achieved by inducing the differentiation of Tfh cells through their action on the cytokine IL-12. These bacteria also produce EPSs, modulating the intestinal microbiota [27,28]. As for Pediococcus, the main strain exploited as a producer of postbiotics is Pediococcus acidilactici due to its growth properties at different pH values, temperatures, and osmotic pressures; it is therefore adaptable to different conditions, such as those imposed by the human gastrointestinal tract, having homofermentative capacity for the production of lactic acid and bacteriocins, which gives it antimicrobial properties [31,32].

Fermentation by LAB is an anaerobic process, i.e., it occurs in the absence of oxygen, in which these bacteria convert carbohydrates, mainly glucose, into lactic acid, among other products. There are two main types of fermentation in LAB: homofermentative, in which the final product is exclusively lactic acid; and heterofermentative, in which, in addition to lactic acid, by-products such as ethanol, acetic acid, and carbon dioxide are also produced. In addition to lactic acid, other bioactive substances can be generated during fermentation, such as short-chain fatty acids (SCFAs), vitamins, EPSs, biosurfactants, and bacteriocins [33,34,35].

The LAB fermentation process is widely used in food industry due to its contribution to the flavor, texture, and functional properties of foods, in addition to its potential beneficial effects on intestinal health and the immune system [26,36]. It is worth noting that the synthesis of postbiotics can vary according to the bacterial strain used in their synthesis. In addition, they are subject to factors such as physical criteria during fermentation, growth media, and nutrients provided [26,36].

SCFAs are produced from the bacterial fermentation of complex polysaccharides, i.e., non-digestible dietary fibers, the main representatives being butyrate, acetate, and propionate [17,36]. These substances have been shown to be effective in reducing inflammation generated in IBD through the inhibition of histones and the activation of G-protein-coupled receptors. Thus, they present advantages such as influencing cell proliferation, preventing the development of malignant cells, and improving the vitality of enterocytes and colonocytes, in addition to promoting intestinal barrier maintenance [26,36,37].

Studies have shown that butyrate has gene expression modulation properties and an immunosuppressive effect through the regulation of pro-inflammatory cytokines such as IL-1β, IL-6, and tumor necrosis factor (TNF-α). Moreover, it has been observed that it elevates anti-inflammatory mediators, such as IL-10, contributing to anoxidative stress reduction and being a source of energy for the colon mucosa. Thus, it was demonstrated that the dysbiosis associated with patients with IBD was closely linked to the reduction of SCFA, mainly from bacteria that synthesize butyrate, such as bacteria belonging to the phylum Firmicutes [17,37,38,39].

EPSs are biopolymers released by the bacterial cell wall that are responsible for modulating the immune response through the stimulation of dendritic cells and macrophages. They are also known to activate NK cells and increase the proliferation of T lymphocytes, in addition to reestablishing the intestinal barrier function during IBD through the regulation of adhesion proteins that make up tight junctions [17,26,40].

Zhou et al. (2018) [40] demonstrated the ability of EPSs produced by LAB to regulate intestinal barrier integrity during IBD through the activation of a transcriptional factor called STAT3. The antioxidant effects demonstrated by EPSs have also been quite attractive, as they act by neutralizing and eliminating reactive oxygen species (ROS) involved in oxidative stress reactions [26,41].

Postbiotic enzymes also play an important antioxidant role, the main ones being superoxide dismutase, glutathione peroxidase, and NADH peroxidase [14,42]. Oxidative stress represents an imbalance between oxidation and antioxidant processes, with superoxide dismutase being one of the most important enzymes for regulating antioxidant function due to its ability to dismutate the O²⁻ radical, which reduces the concentration of free cations and the damage caused by hydrogen peroxide [43,44].

Organic acids and some postbiotic proteins are relevant due to their antimicrobial effect. The main organic acids produced are lactic acid, propionic acid, and 3-phenyllactic acid, which have shown wide application as antimicrobials. Regarding synthesized proteins, it is worth mentioning bacteriocins and the S-Layer [15,45].

Bacteriocins are synthesized in the ribosomes of LAB as primary metabolites and released into the extracellular environment. They exercise antimicrobial action through the formation of pores in the cell membranes of susceptible pathogens. They can exert a bactericidal or bacteriostatic effect and are classified into classes I, II, and III, where class I and II bacteriocins are resistant to changes in pH and heat, while class III bacteriocins do not have the same resistance [15,26,46].

The other compounds that make up this postbiotic contribute to its overall effectiveness due to their diverse antioxidant, antimicrobial, and anti-catabolic properties, as well as their other properties, as demonstrated in

Table 1. Characterization of main postbiotics generated from lactic acid bacteria fermentation.

Category	Biometabolite	Mechanism	Proprieties	Functionality	References
Short chain fatty acids	Butyrate Acetate Propionate	Histone inhibition and activation of G-protein-coupled surface receptors	Anti-inflammatory, antioxidant, anti-microbial, anti-catabolic	Intestinal barrier maintenance, muscle restoration, protection against pathogens	[36,37,38,39].
Carbohydrates	Exopolysaccharides	Stimulation of dendritic cells and macrophages, neutralization of reactive oxygen species and activation of STAT3	Anti-inflammatory and antioxidant	Immune response modulation, oxidative stress reduction and barrier restoration	[17,26,40,41].
Enzymes	Glutathione peroxidase Superoxide dismutase NADH peroxidase	Dismutation and removal of superoxide and hydrogen peroxide radicals	Antioxidant	Oxidative stress reduction	[14,42,47].
Organic acids	Lactic acid Propionic acid 3-phenyllactic acid	pH reduction	Antimicrobial	Protection against pathogens	[15,45].
Proteins	S-Layer Bacteriocins	Inhibition of adhesion and formation of pores in the membrane of microorganisms	Antimicrobial	Protection against pathogens	[15,26,46,48].
Vitamins	Vitamin B Vitamin K	Enzymatic cofactors	Maintains homeostasis	Cellular maintenance	[15,49].
Biosurfactants	-	Inhibition of adhesion of microorganisms	Antimicrobial	Protection against pathogens and inhibition of biofilm formation	[15].

.

The use of postbiotics in the nutraceutical, pharmaceutical, and food industries has shown promise due to their health benefits. However, large-scale production still faces challenges [13,14].

The production of postbiotics occurs through controlled fermentation using specific LAB (lactic acid bacteria) strains. The required conditions involve cultivation in MRS media or modified media, under anaerobic or microaerophilic atmospheric conditions, at temperatures between 30 and 37 °C and pH values between 5.0 and 6.5, depending on the desired postbiotic. Postbiotic production has advanced with the use of various modern biotechnological techniques aimed at increasing efficiency, standardization, and bioactivity [50,51].

The use of bioreactors with automated control is employed in the production of EPSs, bacteriocins, and organic acids. This technique allows the real-time monitoring of pH, temperature, oxygen, and substrates to optimize the process and increase productivity [52]. However, the use of bioreactors for large-scale fermentation still faces limitations, such as low tolerance to temperature variations [44,45].

Techniques such as spray-drying, freeze-drying, and alginate encapsulation have contributed to improving the stability of sensitive postbiotics, such as antioxidant enzymes and bioactive peptides. According to Thorakkattu et al. (2022) [14], freeze-drying is one of the most promising ways to commercialize these compounds, although this process may affect their stability and antimicrobial properties. On the other hand, microencapsulation techniques ensure proper storage and prolonged release (Jin et al., 2025) [53].

Thus, controlled industrial fermentation emerges as a viable alternative for the production of active postbiotics [13], as shown in Figure 1. Furthermore, the production of compounds such as EPSs by LAB has proven to be commercially unviable due to low yield [54].

3. Pathophysiology of Muscular Complications in Inflammatory Bowel Disease

Sarcopenia, characterized by the progressive loss of skeletal muscle mass and strength, is a growing concern in patients with IBDs, such as Crohn’s disease and ulcerative colitis. The prevalence of sarcopenia in patients with IBD is significantly higher than that in healthy individuals. It is estimated that approximately 51% of patients diagnosed with IBD show signs of muscle wasting [46,50]. Compared to the general population, where the prevalence of sarcopenia ranges from 5% to 13% in people aged 60 to 70 years, patients with IBD have an increased risk of developing this condition, with data revealing that prevalence can reach 65% in some groups [55].

Systemic and localized inflammation plays a key role in the muscle degeneration observed in patients with IBD, as demonstrated in Figure 2. Chronic inflammation in the intestine activates a systemic inflammatory response, promoting the release of inflammatory mediators that directly impact muscle integrity. Steell et al. (2021) [56] highlighted that intestinal inflammation, characteristic of IBD, results in an increase in intestinal permeability, facilitating the translocation of endotoxins into systemic circulation. This process aggravates systemic inflammation, leading to the activation of catabolic pathways, such as NF-kB pathway, which is directly involved in muscle degradation.

Furthermore, chronic inflammation results in increased levels of cortisol, a catabolic hormone that is released in response to inflammatory stress. As discussed by Nishiwaka et al. (2021) [4], increased cortisol in circulation favors the degradation of muscle proteins and reduces the synthesis of skeletal proteins, contributing to the development of sarcopenia.

Local inflammation in the intestine also increases the production of cytokines such as IL-6 and TNF-α, which have a direct effect on skeletal muscle, promoting resistance to protein synthesis and increasing muscle degradation [57]. The ubiquitin–proteasome proteolytic pathway is a primary cellular mechanism responsible for the selective degradation of damaged or unneeded proteins. In this process, proteins are tagged with ubiquitin molecules and subsequently directed to the proteasome, a protein complex that breaks them down. This pathway plays a crucial role in regulating muscle protein turnover, particularly during inflammation and muscle wasting conditions [58]. Muscle loss in patients with IBD is also often associated with insulin resistance and increased basal energy expenditure, processes that contribute to the metabolic imbalance that characterizes these conditions [59].

Increased basal energy expenditure in IBD patients can lead to excessive muscle catabolism, as the body uses muscle protein as an energy source. This phenomenon is particularly concerning in malnourished patients, who may have a reduced ability to mobilize fat and protein stores to support muscle function [55].

Moreover, intestinal malabsorption, common in individuals with IBD, makes it difficult to obtain essential nutrients, such as proteins and amino acids, which are fundamental for maintaining muscle mass. Leucine, an essential branched-chain amino acid, plays a crucial role in activating the mTOR pathway, which promotes muscle protein synthesis. In patients with IBD, leucine deficiency is one of the main factors contributing to muscle mass loss, since the insufficient intake of this amino acid results in a reduced anabolic response in the muscles [59].

In addition to leucine, other nutrients such as vitamin D play an important role in muscle health and sarcopenia prevention. Vitamin D is involved in regulating muscle function and promoting muscle protein synthesis, and is an important factor in maintaining muscle mass in patients with inflammatory diseases. Thus, vitamin D deficiency is common in patients with IBD, which worsens the loss of muscle mass and weakness associated with sarcopenia [55].

Insufficient protein intake may also be associated with the clinical condition of these patients, who have difficulty consuming the appropriate amount due to abdominal pain, distension, and other gastrointestinal symptoms. Studies show that approximately 40% of older patients with IBD do not reach the recommended daily protein intake, which contributes to the muscle deterioration observed in these individuals [59].

Thus, the protein destruction observed in many IBD patients further compromises the capacity for muscle regeneration, in addition to being associated with a higher rate of hospitalizations and postoperative complications [4]. With the loss of muscle mass and the resulting fragility, these patients become more vulnerable to falls, fractures, and an increased risk of premature death. Therefore, the nutritional management of these patients should include not only the correction of dietary deficiencies, but also strategies to improve the absorption of essential nutrients.

4. Application of Postbiotics Derived from Lactic Acid Bacteria in Muscular Complications

The application of postbiotics derived from lactic bacteria has shown great potential in alleviating muscle complications, particularly due to their immunomodulatory, anti-inflammatory, and antioxidant properties (Figure 3) [60,61,62,63].

In general, postbiotics comprise a broad range of bioactive compounds that exert beneficial effects on host health through distinct molecular pathways (as detailed in Table 1). SCFAs, such as butyrate, acetate, and propionate, modulate inflammation and muscle metabolism through histone deacetylase inhibition and the activation of G-protein-coupled receptors (GPR41 and GPR43), enhancing intestinal barrier function and promoting muscle regeneration [36,37,38,39]. Exopolysaccharides, derived from lactic acid bacteria, activate immune cells and neutralize reactive oxygen species via the STAT3 signaling pathway, contributing to oxidative stress reduction and mucosal healing [17,26,40,41]. Antioxidant enzymes like superoxide dismutase and glutathione peroxidase scavenge free radicals, limiting tissue damage in chronic inflammatory states [14,42,47]. In addition, organic acids, bacteriocins, and biosurfactants demonstrate antimicrobial effects by lowering pH or disrupting pathogen membranes, while vitamins serve as enzymatic cofactors essential for cellular maintenance [15,45,46,48,49]. The integrated action of postbiotic metabolites underscores their therapeutic relevance in IBD treatment, especially in mitigating inflammation-driven muscle wasting.

Among the most studied postbiotics, SCFAs such as butyrate, acetate, and propionate are recognized for their key roles in inflammation control and redox balance. These compounds help to neutralize skeletal muscle damage, enhancing muscle repair and regeneration. Studies suggest that SCFAs may also act as metabolic modulators by activating G-protein-coupled receptors (GPR41 and GPR43), leading to the secretion of gut peptides that improve insulin sensitivity and increase glucose uptake in muscle tissue [63,64,65,66].

Butyrate, specifically, has demonstrated benefits in inflammatory modulation, mitochondrial function preservation, and energy metabolism regulation [61]. Its action on PI3K/AKT/mTOR signaling pathways and antioxidant capacity has been associated with muscle mass maintenance [60,61]. Acetate activates AMPK and supports mitochondrial biogenesis, while propionate influences lipid and glucose metabolism, contributing to gut barrier integrity and the modulation of inflammatory responses, factors considered essential in the management of sarcopenia [61,64,67].

Additional studies have evaluated the effects of Lactobacillus-derived postbiotics in muscle atrophy models. Jeong et al. (2024) [63] demonstrated that thermally processed Lactiplantibacillus plantarum postbiotics improved muscle mass and function through anti-inflammatory and anti-catabolic mechanisms. In another study, the use of sodium butyrate and ReFerm (a L. plantarum-derived product) significantly reduced clinical symptoms and improved quality of life in patients with irritable bowel syndrome [68].

Furthermore, protein fractions from Lactobacillus delbrueckii CIDCA 133 postbiotics promoted mucosal healing, reinforced the intestinal epithelial barrier, and corrected dysbiosis in a murine model of 5-fluorouracil-induced mucositis, in addition to reducing inflammatory cytokine levels [69].

Other studies, such as the work of Han et al. (2023) [70], examined the use of polyphenol-rich melon peel extract and whey fermented with Lentilactobacillus kefiri (DH5) in mice. These interventions resulted in the attenuation of muscle atrophy, improved myotube morphology, and the modulation of the gut microbiota. The observed benefits were attributed to an increase in butyrate-producing microorganisms, reinforcing the importance of this SCFA in muscle health.

Moreover, bacteriocins produced by certain LAB strains inhibit intestinal pathogens, contributing to microbiota equilibrium and enhancing nutrient absorption important for muscle metabolism, while exopolysaccharides (EPSs) exert immunomodulatory effects, reducing systemic inflammation linked to sarcopenia and supporting muscle function [60,71,72].

Recent studies have revealed that the therapeutic effects of postbiotics are not limited to isolated mechanisms, but also involve synergistic interactions that enhance their efficacy (Figure 4). For instance, short-chain fatty acids (SCFAs), such as butyrate, acetate, and propionate, not only exert anti-inflammatory and antioxidant activities, but also interact with intracellular signaling pathways. Butyrate has been shown to activate the PI3K/AKT/mTOR axis, promoting muscle protein synthesis and the preservation of muscle mass [36,39]. Acetate stimulates AMPK and mitochondrial biogenesis, which supports energy metabolism and reduces muscle atrophy [36,37,38,39,61,64,67]. These SCFAs also improve intestinal barrier integrity and reduce systemic inflammation, which are key factors in muscle catabolism associated with IBD [36,37,38,39]. These synergistic effects amplify the physiological responses to postbiotic supplementation, particularly in the context of IBD-related sarcopenia, where chronic inflammation and dysbiosis impair muscle homeostasis.

Thus, these postbiotics, due to their multifaceted biological actions, represent promising therapeutic candidates for the management of sarcopenia, particularly in elderly populations or individuals with inflammatory and degenerative muscle conditions.

5. Postbiotics as Adjuvant Therapy in the Management of Muscular Complications of Inflammatory Bowel Disease

The management of muscular complications in IBD requires an integrated approach, combining nutritional and pharmacological therapies with emerging strategies such as postbiotic supplementation [62,73].

The integration of postbiotics with nutritional therapies can optimize the absorption and utilization of nutrients essential for muscle protein synthesis [74,75]. In the context of pharmacological treatment, postbiotics may serve as adjunctive agents, enhancing the effects of conventional therapies for IBD. The prolonged use of corticosteroids and TNF-α inhibitors, although essential for controlling inflammation, can lead to adverse effects such as insulin resistance and muscle atrophy; postbiotics may help to mitigate these effects by modulating gut inflammation and supporting metabolic balance [76].

Table 2. Interaction between postbiotic, nutritional, and pharmacological therapies in inflammatory bowel disease.

	Therapeutic Component	Objective	Example	Synergistic Benefits	Potential Adverse Effects/Limitations	References
Biotic therapy	Postbiotics	Reduction in inflammation and mitochondrial improvement	Short-chain fatty acids, exopolysaccharides, bacterial peptidoglycans	Reduced inflammation, improved cellular function	Individual responses vary, need for standardization	[70,80].
Nutritional therapies	Protein diet	Stimulation of protein synthesis	Leucine, whey protein	Muscle mass recovery and maintenance	Risk of renal overload in patients with renal failure	[78,79].
	Omega-3 and antioxidants	Oxidative stress reduction and inflammation	Supplementation with omega-3, vitamin E	Reduced muscle damage and chronic inflammation	Possible interactions with anticoagulants	[80,81].
Biotic therapy	Anti-inflammatories	Control of intestinal inflammation	Mesalazine, corticosteroids	Reduced intestinal inflammatory activity	Adverse effects such as osteoporosis and insulin resistance	[82,83].
	Immunosuppressants	Modulation of the immune response	Azathioprine, infliximab	Prevention of inflammatory flare-ups and muscle protection	Increased risk of infections and systemic adverse effects	[77,84,85].

summarizes the main interactions between postbiotics, nutritional and pharmacological therapies, highlighting their synergistic benefits and potential limitations [77,78,79,80,81,82,83,84,85].

Advances in research on postbiotic administration may lead to the optimization of formulations and the development of personalized therapies, thereby increasing the effectiveness of postbiotics in addressing muscle-related complications in IBD. The combination of these strategies with nutritional and pharmacological interventions could represent a significant step forward in the therapeutic management of these patients [86,87].

Table 3. Postbiotic administration strategies and their impacts on bioavailability.

Form of Administration	Example of Postbiotic	Advantages	Challenges	Bioavailability	References
Food supplements	Short-chain fatty acids, bioactive peptides	Precise dosage control, convenience	Need for standardization of the ideal dose	Medium, depends on formulation and intestinal absorption	[79,80].
Functional foods	Postbiotics enriched in yogurts, fermented beverages	Good consumer acceptance, easy daily consumption	There may be degradation of bioactive compounds	Variable, influenced by digestive processes	[79,81,82].
Nutritional formulas	Mixture of metabolites derived from Lactobacillus and Bifidobacterium	Indicated for patients with eating difficulties	High cost and lower adherence in healthy individuals	High, due to formulation optimized for absorption	[77,79].
Nanotechnology	Nanoencapsulation of postbiotics	Increases bioavailability and protection of compounds	Technology still under development, high cost	Very high, protection against gastric degradation	[77,83].

summarizes the main postbiotic administration strategies and their impacts on bioavailability and therapeutic efficacy.

Postbiotics can be incorporated into different carriers to ensure their stability and absorption. Supplements in capsules or soluble powders offer precise dosing and are often used in standardized formulations containing SCFAs, antimicrobial peptides, and bioactive polysaccharides [88]. These compounds have high bioavailability and can be formulated for controlled release, enabling sustained action throughout the gastrointestinal tract [89].

A complementary strategy involves the incorporation of postbiotics into functional foods, such as fermented yogurts, dairy drinks, and nutritional bars. In addition to facilitating patient adherence to treatment, these foods can act synergistically with other essential nutrients, such as high-quality proteins and antioxidants [90]. However, the stability of postbiotics in these products must be considered, as fluctuations in pH and temperature can compromise biological functionality [88,91].

The bioavailability of postbiotics can also be improved through technologies such as microencapsulation and the use of polymeric nanoparticles, protecting bioactive compounds against enzymatic degradation and ensuring targeted delivery to the small intestine and colon. These strategies are essential to ensure that postbiotics reach the site of action with maximum efficacy [86,92].

Furthermore, attention should be paid to the dose when applying postbiotics. Defining the ideal dosage still requires more robust clinical studies, but preliminary evidence suggests that concentrations between 10⁸ and 10¹¹ CFU/mL (or their metabolic equivalents) may be effective in reducing inflammation and supporting muscle mass maintenance in patients with IBD [92]. Therefore, tailoring treatment based on the individual intestinal microbiota profile represents a promising future direction to maximize the therapeutic potential of postbiotics [87,89].

6. Challenges and Limitations in the Use of Postbiotics for Muscular Complications in Inflammatory Bowel Disease

The use of postbiotics for the management of muscular complications in patients with inflammatory bowel diseases (IBDs) is emerging due to their promising pharmacotherapeutic potential. In particular, postbiotics have shown potential in mitigating sarcopenia—a frequent and debilitating complication in IBD patients—by modulating inflammation and supporting muscle metabolism. However, limitations must be considered and challenges must be overcome for their safe and effective use [63].

During the LAB (lactic acid bacteria) selection process for postbiotic production, it is necessary to analyze and consider factors that alter the chemical composition of postbiotics, as these factors can affect their behavior and decrease the growth rate. The specificity of lactic bacteria is widely reported in the literature, with emphasis on the production of organic acids regardless of genus, but considering the specific strain used—an important consideration when tailoring postbiotics for muscle health in IBD patients [93].

Another important factor is the technology used in the microbial inactivation process. Recent studies have shown that different thermal treatments (air drying, spray drying, freeze-drying) directly and significantly impact the viability, availability, and immunomodulatory properties of postbiotics. Thus, heat-based processing may reduce their therapeutic potential, especially when targeting complex conditions like sarcopenia in IBD [94]. On the other hand, emerging non-thermal technologies—such as ionizing radiation, electric field treatment, magnetic field heating, and ultrasonication—have demonstrated promise in preserving functional compounds while improving stability and bioavailability [95].

Another critical challenge is the high degree of individual variability among IBD patients, including differences in gut microbiota composition, genetic predispositions, age, and nutritional status—all of which influence muscle health and responses to postbiotic therapy [96]. Furthermore, IBD itself disrupts gut homeostasis and absorption, reinforcing the need for personalized therapeutic strategies that ensure the selection of functional bacterial strains and effective delivery methods tailored to muscle recovery [14].

The interaction between administered postbiotics and the existing human microbiome can also result in unexpected outcomes, such as metabolite inactivation, toxicity, or dysbiosis, potentially compromising therapeutic goals like inflammation control and muscle preservation. Moreover, manipulating specific metabolites in the gut may disrupt homeostasis and impair endogenous synthesis. These concerns highlight the importance of identifying specific bioactive compounds produced by native LAB strains and assessing their compatibility with supplemented postbiotics before therapeutic application [97].

Therefore, it is of the utmost importance to analyze in vitro and in vivo results to establish a relationship with the unique characteristics of the human intestine, especially the colon. Through these clinical studies and biochemical evaluations, more precise mechanisms by which postbiotics support muscle recovery in IBD can be elucidated [98].

Regulatory clarity is another challenge. The US Food and Drug Administration has not specifically addressed postbiotics and will most likely evaluate them according to the category under which a product falls. The product’s safety and efficacy must meet all standards for medical and pharmacotherapeutic use [14]. The European Medicines Agency [99], for instance, only approved bacterial lysates for the prevention of recurrent respiratory infections, not for other uses, including IBD-related conditions—highlighting the current regulatory limitations as regards expanding the application of postbiotics to sarcopenia in IBD.

Further research is considered essential to establish the relationship between the efficacy and prophylactic effects of postbiotics. Studies that integrate multiple methodological perspectives, such as large-scale clinical trials, double-blind, longitudinal studies, are needed to verify the potential of postbiotics as adjuvants in muscle recovery and preservation in patients with IBD-associated sarcopenia. In addition, it is recommended to conduct research exploring strain combinations and improved formulation techniques tailored to muscle anabolism, aiming to accelerate recovery or adapt therapy to individual patient needs [12].

7. Future Perspectives on the Use of Postbiotics Derived from Lactic Acid Bacteria

Postbiotics have gained prominence due to their therapeutic potential in the treatment of several conditions, particularly in addressing muscle wasting associated with inflammatory bowel disease (IBD). In the context of IBD-associated sarcopenia, chronic inflammation and gut dysbiosis play a critical role in accelerating muscle catabolism, highlighting the need for targeted interventions. With the postbiotics market expected to reach $91.7 billion by 2030, there is growing interest in developing formulations specifically aimed at modulating the gut–muscle axis in IBD patients. Advances such as microencapsulation and genetic engineering have the potential to improve the stability and efficacy of these compounds, enhancing their targeted delivery to sites of intestinal inflammation and maximizing therapeutic effects in muscle preservation [100,101].

Postbiotics can act as key modulators of the intestinal microbiome and inflammatory responses, both of which are closely linked to sarcopenia in IBD. This therapeutic strategy offers promise for mitigating muscle catabolism driven by dysbiosis and systemic inflammation [8]. Regarding sarcopenia, targeted postbiotic interventions, including supplementation with SCFAs and fermented foods rich in bioactive metabolites, have shown the capacity to improve muscle health in IBD patients. Intestinal microbiome modulation through probiotics, prebiotics, and postbiotics can positively impact essential metabolic processes, such as protein metabolism and mitochondrial function, helping to counteract the catabolic effects of inflammation and promote muscle mass maintenance or gain [102]. This innovative approach not only offers an alternative to conventional treatment, but represents a promising path toward individualized therapy and precision medicine for patients suffering from both IBD and sarcopenia.