Search Results (565)

Background/Objectives: The gut microbiota is increasingly recognized as a key determinant of human health, playing a vital role in metabolism, immunity, and disease susceptibility. Dysbiosis, or microbial imbalance, is associated with gastrointestinal disorders such as irritable bowel syndrome (IBS), inflammatory bowel disease (IBD), and Clostridioides difficile infection (CDI), as well as extraintestinal conditions, including obesity, cardiovascular disease, and neuropsychiatric disorders. This review aims to provide an updated overview of emerging therapeutic strategies to modulate the gut microbiota to restore eubiosis and improve health outcomes. Methods: A narrative review of recent literature was conducted, focusing on preclinical and clinical studies investigating microbiota-targeted therapies. The review primarily covers innovative interventional approaches, including fecal microbiota transplantation (FMT), bacterial consortium transplantation (BCT), bacteriophage therapy and outer membrane vesicles (OMVs). Results: Evidence supports the role of probiotics, prebiotics, and synbiotics in remodeling microbial communities and improving host health, although their effects may be strain- and context-dependent. FMT has demonstrated high efficacy in the treatment of recurrent Clostridium difficile infections and is being studied for IBD, IBS and extraintestinal diseases, following the recent Food and Drug Administration approval of the first commercial FMT products. BCT offers a standardized alternative to donor-derived material, with early clinical successes such as FDA-approved SER-109. Phage therapy and OMVs represent promising frontiers, offering targeted microbial modulation and interactions with the immune system, although clinical data remain limited. Conclusions: Emerging gut microbiota modulation strategies offer new perspectives for precision medicine and could transform the prevention and treatment of many diseases, but further studies are needed to ensure their safety, standardization, and clinical application. Full article

Weaning is a critical developmental stage in puppies often accompanied by gastrointestinal disturbances and empiric antibiotic use. This double-blind, placebo-controlled trial evaluated the safety and efficacy of two canine milk-derived probiotic strains, Lacticaseibacillus rhamnosus CECT 30021 and Lactiplantibacillus plantarum CECT 30022, in recently weaned Labrador Retriever puppies. Forty-nine healthy puppies were enrolled and allocated to receive a daily capsule containing either strain alone, a combination of both, or placebo for six weeks, followed by a six-week observation period. Probiotic supplementation was well tolerated, and clinical, hematological, and biochemical parameters remained within normal ranges. Compared with placebo, the probiotic-treated puppies experienced fewer gastrointestinal infections and required less antibiotic therapy. Supplementation helped maintain normal fecal consistency, prevented increases in fecal calprotectin and inflammatory cytokines, and produced significantly higher fecal short-chain fatty acid concentrations. Systemically, probiotic intake was associated with lower serum cortisol, IL-8, TNF-$\alpha$, and cholesterol, and stronger antibody responses to vaccination. Probiotic-supplemented puppies also showed faster weight gain during treatment, and this difference persisted after supplementation ended. Overall, these findings indicate that both strains, administered individually or in combination, safely support gastrointestinal, metabolic, endocrine, and immunological health in Labrador Retriever puppies during weaning and may help reduce the need for antibiotics. Full article

Background/Objectives: The prevalence of the commensal gut bacterium species, Phascolarctobacterium faecium, has been associated with normal weight in humans. Preclinical evidence suggests that the strain P. faecium DSM 32890 exerts beneficial effects on metabolic and immune function in diet-induced obesity. Herein, we aimed to evaluate the safety and tolerability of this strain in a preclinical study and a pilot interventional trial in humans. Methods: A repeated-dose oral toxicity study of 28 days was performed in Wistar rats (male and female), during which adverse signs and clinical outcomes were assessed, along with histological, hematologic, biochemical, and immune markers. Subsequently, a pilot human intervention trial was conducted, including 20 participants (11 overweight and 9 normal weight) who received P. faecium DSM 32890 daily for 15 days. Body composition, dietary intake, physical activity, clinical data, perceived health, gastrointestinal symptoms, and blood analyses were assessed to determine tolerability and identify potential adverse effects. Results: In rats, the administration of the bacterium did not cause behavioral, physiological, histologic, immune, or biochemical alterations. In humans, there was no evidence of adverse effects on general health, hematological and biochemical profiles, bowel habits, or gastrointestinal symptoms. Overweight participants experienced reductions in flatulence and nausea after the intervention. Conclusions: The consumption of P. faecium DSM 32890 did not raise safety concerns and was well tolerated in rats and humans. The findings represent a step forward in the path toward future, longer-term studies to explore the potential efficacy. Full article

Background/Objectives: Casein glycomacropeptide (cGMP) has been modified to enable its suitability as a low phenylalanine (Phe) protein substitute (PS) in phenylketonuria (PKU). No data is available about its global usage. Methods: A 60-item multiple choice and short answer/extended response questionnaire examining the use of modified cGMP in PKU was distributed globally to dietitians and physicians via web-based professional inherited metabolic disorder groups. Results: Respondents (n = 208) from 45 countries across 6 continents completed the questionnaire. Of these, 83.7% (n = 174) were dietitians/nutritionists, 14.9% (n = 31) medical doctors/physicians and 1.4% (n = 3) other health professionals, caring for both paediatric and adult patients (59.1%), paediatrics only (25.0%) or adults only (15.9%). cGMP PS were reported as not available in their centre/hospital by 19.7% (n = 41), mostly in Africa, South America, and southern and western Asia. The main reasons included lack of regulatory approval (65.8%), not promoted by manufacturers (41.5%), and cost (29.3%). An estimated 25% of represented patients globally were using cGMP PS; 78.4% (n = 163) following refusal/poor adherence with Phe-free amino acids and 54.8% (n = 114) for adult patients recommencing dietary treatment. There were concerns about the residual Phe in cGMP negatively impacting blood Phe levels in children <12y (66.3%), adolescents (48.0%), adults (34.6%), and the first trimester of pregnancy (53.1%). Sixty nine percent (n = 145) adjusted dietary Phe prescription according to the cGMP Phe content, particularly in regions with a higher percentage of severe PKU variants. Commonly perceived clinical advantages with cGMP were improved taste/palatability (93.2%, n = 194) and fewer gastrointestinal symptoms (55.8%, n = 116). Perceived clinical disadvantages were residual Phe (72.1%, n = 150), lack of data in children < 3 years (48.1%, n = 100), and the high energy content of some brands (45.2%, n = 94). There were concerns that cGMP PS were too high in sugar (34.1%, n = 71) and dissatisfaction or uncertainty about the adequacy of its Phe (66.3%) and amino acid (34.1%) content. Conclusions: There is global inconsistency in access to cGMP PS suitable for PKU, and in the interpretation of evidence-based research. Some professionals have significant concerns about its nutritional composition particularly residual Phe, limiting its estimated use to approximately 25% of PKU patients globally. Full article

Faced with the challenge of reducing food waste, transforming discarded fruit into functional ingredients useful for the food industry is a valuable solution. Ingredients from fruit such as persimmons, which are rich in indigestible carbohydrates and bioactive compounds with antiradical capacity, could positively impact on the health of certain population groups due to their potential prebiotic effect. This study aimed to select the most suitable drying conditions and milling intensity for obtaining powdered persimmon ingredients with a prebiotic-like effects observed in vitro for postmenopausal women, and to evaluate this effect by considering the stimulation of health-promoting bacterial growth and short-chain fatty acids (SCFAs) production. First, the effect of the drying method (hot air drying at 60 and 70 °C, and freeze-drying) and grinding intensity on antiradical capacity, particle size, and the release of bioactive antiradical components into the intestinal lumen after an in vitro gastrointestinal digestion was determined. Next, the effect of these conditions on the microbiota composition of postmenopausal women was preliminary assessed in a batch colonic fermentation experiment for 24 h. The results showed that the ingredient dried with air at 70 °C had the highest phenol and flavonoid content, suffered the least degradation during in vitro gastrointestinal digestion and promoted the differential growth of fiber-degrader genera. Consequently, this was the ingredient selected as the most suitable. Lastly, the impact of this ingredient on the microbiota composition of 4 postmenopausal women has been evaluated in a long-term study using the Simulator of the Human Intestinal Microbial Ecosystem (SHIME^®) coupled to high throughput sequencing. The growth stimulation of health-associated bacteria, such as Akkermansia muciniphila, Faecalibacterium prausnitzii or Phascolarctobacterium faecium, and the promotion of beneficial metabolic pathways, such as the sugar uptake-specific phosphotransferase system, sugar metabolism and propionate and isobutyrate production, were detected along 14 days of persimmon powder supplementation. A holistic framework for promoting human health while advancing environmental sustainability is represented by the combination of sustainable by-product valorization and microbiota-targeted functional food development. Full article

The family Lactobacillaceae, reclassified in 2020 into 25 genera comprising 261 species, remains one of the most extensively studied groups of lactic acid bacteria (LAB) due to its wide distribution in fermented products, commensal presence in the gastrointestinal tract, and studied health effects. Long classified as “generally recognized as safe (GRAS)” by the U.S. Food and Drug Administration (FDA), these organisms not only contribute to the flavor, texture, and preservation of fermented foods and beverages but also provide important health benefits as probiotics. Their metabolic versatility allows them to produce lactic acid, bacteriocins, and other bioactive compounds that inhibit pathogenic microorganisms and enhance food quality. This review provides a comprehensive overview of the functional roles of members of the Lactobacillaceae family in the context of the food matrix in fermentation, health, and biotechnology, and examines recent advances in functional genomics, metabolomics, and extracellular vesicle research to highlight future directions for leveraging these microorganisms in sustainable and innovative applications. Full article

Dietary fiber and phenolic compounds are key bioactives in gastrointestinal and metabolic health; however, their compositional features and metabolic implications have rarely been studied as an integrated system within realistic food matrices. Mango bagasse confectionery previously demonstrated prebiotic potential, and its reformulation with extruded mango peel showed hepatoprotective effects linked to gut microbiota modulation. In this study, mango bagasse and peel confectionery (MBPC) was characterized and its metabolic impact was evaluated in vivo. Wistar rats were fed standard or high-fat diets with or without MBPC supplementation, followed by fecal fatty acid analysis. MBPC exhibited a high dietary fiber content for a confectionery product (25 g total fiber per 100 g), with monomeric profiles indicative of cell wall-derived polysaccharides and pectic components. The fiber fraction showed a low Mw (14.71 ± 0.02 kDa), suggesting a matrix favorable for fiber–phenolic interactions. Phenolic profiling revealed substantial concentrations of free (9.0 mg/mL) and bound (16.7 mg/mL) phenolic compounds. Fecal fatty acid profiles were diet-dependent, with palmitic acid showing the highest relative abundance, followed by stearic, oleic, and linoleic acids, associated with dietary fiber intake. This study elucidates the structural and metabolic relevance of dietary fiber–phenolic interactions within a formulated food matrix. Full article

Aging is accompanied by progressive gastrointestinal structural and functional decline, increased intestinal permeability, dysbiosis, and impaired mucosal immunity, collectively elevating susceptibility to infections, chronic inflammation, and multimorbidity. These age-related changes are further exacerbated by polypharmacy, metabolic disorders, and lifestyle factors, positioning the gastrointestinal tract as a central driver of systemic physiological decline. Gut-centered interventions have emerged as critical strategies to mitigate these vulnerabilities and support healthy aging. Dietary modulation, prebiotic and probiotic supplementation, and microbiota-targeted approaches have demonstrated efficacy in improving gut microbial diversity, enhancing short-chain fatty acid production, restoring epithelial integrity, and modulating immune signaling in older adults. Beyond nutritional strategies, non-nutritional interventions such as molecular hydrogen and medical ozone offer complementary mechanisms by selectively neutralizing reactive oxygen species, reducing pro-inflammatory signaling, modulating gut microbiota, and promoting mucosal repair. Hydrogen-based therapies, administered via hydrogen-rich water or inhalation, confer antioxidant, anti-inflammatory, and cytoprotective effects, while ozone therapy exhibits broad-spectrum antimicrobial activity, enhances tissue oxygenation, and stimulates epithelial and vascular repair. Economic considerations further differentiate these modalities, with hydrogenated water positioned as a premium wellness product and ozonated water representing a cost-effective, scalable option for geriatric gastrointestinal care. Although preclinical and early clinical studies are promising, evidence in older adults remains limited, emphasizing the need for well-designed, age-specific trials to establish safety, dosing, and efficacy. Integrating dietary, microbiota-targeted, and emerging non-nutritional gut-centered interventions offers a multimodal framework to preserve gut integrity, immune competence, and functional health, potentially mitigating age-related decline and supporting overall health span in older populations. Full article

Background/Objectives: Prebiotics, which are non-digestible compounds that selectively modulate gut microbiota, are recognized for their potential to promote host health. Although their bifidogenic effect is well documented, a systematic synthesis of how this microbial modulation translates into clinical gastrointestinal (GI) and metabolic outcomes across diverse populations is needed. This review aims to integrate mechanistic insights with clinical evidence to elucidate the pathway from prebiotic structures to tangible health benefits. Methods: This comprehensive narrative review details the structural properties of major prebiotics (e.g., inulin, FOS, and GOS) that govern their fermentation and the production of short-chain fatty acids (SCFAs). To evaluate clinical efficacy, an analysis of 22 randomized controlled trials from the past decade was conducted, focusing on human studies that utilized ISAPP-recognized prebiotics as the sole intervention. Results: The analysis confirms that prebiotic supplementation consistently increased the abundance of beneficial bacteria (e.g., Bifidobacterium and Lactobacillus) and SCFA production. These changes are associated with significant clinical improvements, including enhanced stool frequency and consistency, strengthened intestinal barrier function, and modulated immune responses. Benefits have been documented in healthy individuals, children, the elderly, and those with conditions such as constipation, metabolic syndrome, and antibiotic-associated dysbiosis. However, significant inter-individual variability in response was evident, and the study designs showed notable heterogeneity in prebiotic type, dosage, and duration. Conclusions: Prebiotics are effective modulators of gut health, driving clinical benefits through selective microbial fermentation and SCFA production. The documented heterogeneity and variability highlight the need for future research to focus on personalized nutritional strategies. Key priorities include standardizing intervention protocols, elucidating dose–response relationships, integrating multi-omics data to link taxonomy to function, and exploring novel applications such as synbiotic formulations and gut–brain axis modulation. Full article

Background/Objectives: This study examines the application of the novel double emulsion gel system for the delivery and release of encapsulated cannabidiol (CBD) and the probiotic strain Lactiplantibacillus plantarum DSM 24624. Methods: During a six-week experimental period comprising stabilization, treatment, and wash-out phases, the dynamic Simulator of the Human Intestinal Microbial Ecosystem (SHIME^®) model was employed to assess a system. The evaluation focused on the delivery of CBD and probiotics, as well as the system’s effects on microbial composition, diversity, and metabolic activity throughout the digestion process using 16S rRNA gene sequencing and digital PCR methods. Results: Microbial community analysis revealed significant shifts in both mucosal and luminal microbiota following supplementation. The treatment increased beneficial bacterial families such as Lachnospiraceae and Clostridiaceae, demonstrated effective delivery, release, and persistence of the probiotic L. plantarum, as well as enhanced butyrate and lactate production. Diversity analyses highlighted a transient rise in alpha diversity within the mucin layer and a decrease in the lumen, with significant changes in beta diversity across experimental phases. Conclusions: Findings suggest that double emulsion gel can be employed for the delivery of probiotics and CBD to the gastrointestinal tract. In addition, an innovative CBD-probiotic formulation can modulate gut microbiota composition and metabolic activity, suggesting its potential as a functional food innovation for intestinal health. However, the results are based on an in vitro model, which lacks the complexity of the human host environment, and further clinical studies are necessary to confirm the biological relevance and therapeutic potential of such delivery systems for gastrointestinal health. Full article

This review highlights the anti-inflammatory and antioxidant effects of probiotics and their complex health-related impacts. The main health areas targeted are gastrointestinal inflammation, neuroinflammation, systemic metabolic disorders, and liver conditions. Probiotics work mechanistically to regulate key inflammatory pathways by suppressing nuclear factor (NF-κb) and mitogen-activated protein kinase (MAPK) pathways and activating antioxidant defenses through nuclear erythroid 2-related factor (Nrf2). They stimulate anti-inflammatory cytokines (including interleukin 10 (IL-10) and inhibit pro-inflammatory mediators such as tumor necrosis factor-α (TNF-α), partly through the regulation of T cells. Probiotics also produce antioxidant metabolites (e.g., exopolysaccharides and short-chain fatty acids), which enhance the host’s resistance to oxidative stress. Supplementation with probiotics improves intestinal inflammation and oxidative injury in gut disorders. Clinical trials suggest that probiotic supplements may reduce neuroinflammation and oxidative stress, while improving cognitive or behavioral outcomes in neurodegenerative disorders. Overall, this review underscores that probiotics have potent anti-inflammatory and antioxidant effects within the gut–brain axis and across various organ systems, supporting their use as valuable adjunctive therapies for inflammatory and oxidative stress-related conditions. It further emphasizes that additional mechanistic research and controlled clinical trials are essential to translate these findings into the most effective therapeutic strategies. Full article

Microplastics (MPs) are considered to be dominant agents responsible for serious contamination in environmental and biological systems. Despite a huge increase in research on these contaminants, there are still considerable uncertainties and progress to be made on the exposure pathways of biological systems, modes of detection, and toxicity assessments. Therefore, developing a critical review of MPs is crucial due to growing evidence of their harmful effects on human health. In the current review, we aim to emphasize the potential toxic effects of MPs on different biological systems in humans, the mechanisms of their toxic effects, and gaps in our knowledge on risk assessment. Importantly, we focus on the risks posed by MPs for fetuses and child health. To ensure methodological rigor, the current review follows the PRISMA guidelines, explicitly detailing the literature search strategy and inclusion/exclusion criteria. The present review summarizes potential sources of MP generation, exposure pathways, quantitative analyses of dietary exposure, estimated daily intake, particle/leachate toxicity evidence, detection in different human organs, and potential toxic effects. MPs cause toxicity in several biological systems in humans, such as the gastrointestinal, nervous, hepatic, endocrine, respiratory, and reproductive systems. In addition, these particles are known to cause oxidative stress, alter metabolism, and affect gut microflora and gastrointestinal functions. Importantly, the current review also discusses the challenges encountered in conducting risk assessments for MPs and the approaches for counteracting these challenges. Finally, the review concludes by recommending future research directions in terms of counteracting the toxic effects of MPs on human health. Full article

Infantile-onset lysosomal acid lipase deficiency (LAL-D) (Wolman disease, historically) is a rare inherited, rapidly progressive disorder caused by pathogenic variants in the LIPA gene, which encodes the enzyme LAL. LAL is essential for the metabolism of cholesteryl esters and triglycerides. LAL deficiency leads to the accumulation of cholesteryl esters and triglycerides within the lysosomes, macrophages, and parenchymal cells in most tissue types, including those in the liver, gastrointestinal tract, and lymph nodes but excluding the central nervous system. Infants with rapidly progressive LAL-D present with gastrointestinal disturbance, adrenomegaly with calcification, hepatosplenomegaly, growth failure due to malabsorption, and systemic inflammation. If untreated, rapidly progressive LAL-D typically leads to death within the first year of life. Treatment takes the two-pronged approach of sebelipase alfa, a human lysosomal acid lipase enzyme replacement therapy (ERT) that improves lipid metabolism, combined with nutritional management. Dietary substrate (lipid) reduction, known as substrate reduction therapy, is essential for optimal management in LAL-D. Following a nutritional plan and managing gastrointestinal disturbances together reduce systemic inflammation and improve growth, gut function, liver health, quality of life, and survival in patients with infantile-onset LAL-D. A multidisciplinary specialized team is necessary to manage the highly complex, multisystemic conditions in these patients. Nutritional management of LAL-D has evolved with increasing experience with the clinical management of ERT-treated infantile-onset LAL-D. A review of guidance for best practice nutritional management is needed. This narrative review aims to provide updated recommendations and guidance for the optimal nutritional management of infantile-onset LAL-D. Full article

Polyphenols, particularly anthocyanins, are associated with metabolic health benefits; however, whether anthocyanin extracts provide greater bioaccessibility than whole foods remain unclear. This study investigated the role of the food matrix in açaí berry, one of the richest natural sources of anthocyanins, by comparing polyphenol and anthocyanin bioaccessibility across freeze-dried whole fruit, crude extract, and purified extract. All samples underwent standardised INFOGEST in vitro digestion, and total polyphenol content (TPC), anthocyanins (ACN), and antioxidant activity were quantified using Folin–Ciocalteu, pH-differential, and DPPH assays, respectively. Intestinal-phase TPC % bioaccessibility was similar in whole fruit (58%) and crude extract (58%) but significantly lower in pure extract (43%). ACN bioaccessibility showed a pronounced matrix effect, with the highest retention in whole fruit (44%), followed by crude extract (32%), and the lowest retention in pure extract (12%). Antioxidant activity after intestinal digestion mirrored these patterns. Overall, these findings demonstrate that the natural açaí food matrix substantially preserves anthocyanin stability during digestion, resulting in higher bioaccessible levels than matrix-free extracts, suggesting that incorporating matrix components into anthocyanin-rich nutraceuticals may help support greater functional recovery during gastrointestinal digestion. Full article

During gastrointestinal digestion, dietary proteins are hydrolyzed into peptides and free amino acids that modulate enteroendocrine function and satiety-related hormone secretion along the gut–brain axis, thereby contributing to obesity prevention. We investigated whey protein concentrate (WPC) as a source of bioactive peptides and evaluated the effects of its digests on cholecystokinin (CCK) secretion in STC-1 enteroendocrine cells by integrating the standardized INFOGEST in vitro digestion protocol, peptidomics (LC–MS/MS), and in silico bioactivity prediction. In STC-1 cells, the <3 kDa intestinal peptide fraction exhibited the strongest CCK stimulation, positioning these low-molecular-weight peptides as promising bioactive components for satiety modulation and metabolic health applications. Peptidomic analysis of this fraction identified short sequences derived primarily from β-lactoglobulin (β-La) and α-lactalbumin (α-La), enriched in hydrophobic and aromatic residues, including neuropeptide-like sequences containing the Glu–Asn–Ser–Ala–Glu–Pro–Glu (ENSAEPE) motif of β-La f(108–114). In silico bioactivity profiling with MultiPep predicted antihypertensive, angiotensin-converting enzyme (ACE)–inhibitory, antidiabetic, dipeptidyl peptidase-IV (DPP-IV)–inhibitory, antioxidant, antibacterial, and neuropeptide-like activities. Overall, digestion of WPC released low-molecular-weight peptides and amino acids that enhanced CCK secretion in vitro; these findings support their potential use in nutritional strategies to enhance satiety, modulate appetite and energy intake, and improving cardiometabolic health. Full article