Search Results (473)

Sarcopenia is an age-related skeletal muscle disorder characterized by reduced muscle mass, strength, and physical performance, as well as increased risk of disability, hospitalization, and mortality. Emerging evidence suggests that gut microbiota alterations may contribute to muscle decline via a microbiota–gut–muscle axis, acting as a context-dependent modulator rather than a primary causal driver. This narrative review synthesizes mechanistic, clinical, and translational evidence linking gut dysbiosis to sarcopenia. Preclinical studies show that microbiota modulation (e.g., antibiotics, probiotics, prebiotics, postbiotics, fecal microbiota transplantation) affects muscle mass, strength, and metabolism through pathways including inflammation, mitochondrial dysfunction, altered short-chain fatty acid production, and impaired anabolic signaling. In humans, observational studies associate lower microbial diversity and reduced short-chain fatty acid-producing taxa with poorer muscle outcomes, but findings are heterogeneous and non-causal. Interventional trials remain limited and characterized by small sample sizes, with effects more consistent for functional outcomes than muscle mass. Overall, the gut microbiota represents a modifiable contributor within the complex biology of sarcopenia. Future studies should integrate microbiome profiling and multi-omics approaches within well-designed clinical trials to identify responder phenotypes and define the role of microbiota-targeted strategies within multimodal interventions. Full article

Increasing evidence suggests pancreatic cancer develops within a host–microbe ecosystem in which microbial communities across anatomical niches interact with tumour biology, immune regulation, metabolism, and therapeutic response. This review examines pancreatic cancer through the lens of humans as holobionts, integrating evidence from the oral, gut, biliary, and intratumoural microbiomes. Epidemiological and sequencing studies demonstrate consistent microbial alterations across these niches in pancreatic cancer, including oral dysbiosis associated with periodontal pathogens, gut microbial shifts toward pro-inflammatory taxa, disease-specific biliary microbial signatures, and the presence of distinct intratumoural microbial communities. Mechanistic studies indicate that intestinal barrier disruption, microbial translocation, immune and metabolite signalling can influence tumour immune architecture, macrophage polarisation, T-cell infiltration, oncogenic signalling pathways, and chemotherapeutic metabolism, particularly inactivation by tumour-associated bacteria. Microbiome-driven shifts in immunometabolism can reprogramme immune-cell metabolic pathways, impairing effective T-cell activation, promoting tumour-supportive macrophage phenotypes. Emerging therapeutic strategies aim to modulate the microbiome–tumour axis, including dietary interventions, probiotics and immunonutrition, faecal microbiota transplantation, engineered microbial therapies, and microbiome-informed antibiotic strategies. While pre-clinical findings are compelling and early-phase clinical studies suggest feasibility, most evidence remains associative and heterogeneous across cohorts and methodologies. Understanding pancreatic cancer as a multi-site ecological system may help explain inter-patient variability in disease progression and treatment response. This could usher in a new era for therapeutic manipulation where future progress will depend on longitudinal, multi-omic, and interventional studies to determine whether microbiome-targeted strategies can produce clinically meaningful improvements in pancreatic cancer outcomes. Full article

Allergic asthma is a prevalent chronic inflammatory disease of the airways whose pathogenesis has traditionally been attributed to localized immune dysfunction within the lung. However, accumulating evidence from microbiome research supports a broader system-level perspective in which cross-organ interactions contribute to disease susceptibility and progression. In particular, the gut–lung axis has emerged as a key regulatory pathway linking intestinal microbial ecology, immune development, and respiratory health. This review synthesizes current epidemiological, mechanistic, and experimental evidence supporting the role of gut microbiota dysbiosis in allergic asthma. We examine how early-life environmental and nutritional exposures and gut microbiota establishment during critical developmental windows shape long-term immune tolerance and asthma susceptibility. We then summarize characteristic features of asthma-associated gut dysbiosis and discuss how microbial-derived metabolites, including short-chain fatty acids, tryptophan metabolites, pro-allergic lipid mediators such as 12,13-dihydroxy-9Z-octadecenoic acid, and bacterial-derived histamine, modulate distal airway immune responses through epigenetic, receptor-mediated, and immune trafficking mechanisms. Particular emphasis is placed on the role of diet as a key upstream regulator of gut microbiota composition and metabolic function. Finally, we evaluate experimental and translational studies targeting the gut–lung axis, including dietary modulation, microbiome-targeted interventions such as fecal microbiota transplantation, and emerging postbiotic approaches. Collectively, current evidence indicates that gut microbial composition and metabolic function are critical determinants of respiratory immune homeostasis. Targeting the gut–lung axis through nutrition- and microbiome-based strategies offers a promising avenue for the prevention and precision treatment of allergic asthma. Full article

Microbiome-based therapies are reshaping the therapeutic landscape for ulcerative colitis (UC), offering new avenues for disease management beyond conventional immunomodulatory and biologic treatments. UC remains a chronic, relapsing condition with significant unmet clinical needs, as many patients fail to achieve sustained remission or experience adverse effects with current therapies. The gut microbiome has emerged as a central contributor to UC pathogenesis, influencing epithelial barrier integrity, immune homeostasis, and metabolic signaling. Interventions such as fecal microbiota transplantation (FMT) and defined microbial consortia have demonstrated proof-of-concept efficacy in early-phase clinical trials, each leveraging distinct mechanistic strategies. FMT, as a broad ecological intervention, restores microbial diversity and functional redundancy, potentially addressing multiple pathogenic mechanisms simultaneously. In contrast, defined consortia enable precise targeting of specific metabolic and immunological pathways, including short-chain fatty acid production, bile-acid remodeling, epithelial barrier reinforcement, immune modulation, and succinate degradation. Recent clinical evidence suggests that consortia with broader mechanistic coverage may achieve more consistent biological activity than narrowly focused designs. This review synthesizes mechanistic and clinical insights across broad and defined microbial consortia, integrates evidence from randomized controlled trials and early-phase LBP studies, and outlines a precision-medicine framework to guide therapy selection. We highlight the importance of aligning therapeutic mechanisms with patient-specific microbial, metabolic, and immune profiles, and discuss future directions including biomarker-guided stratification, hybrid consortia, and adaptive trial designs. Advancing both broad and defined approaches, while incorporating ecological principles, mechanistic understanding, and patient stratification, will be essential to realizing the full therapeutic potential of microbiome-based therapies in UC. Full article

Probiotics, live microorganisms that confer health benefits when administered in adequate amounts, are increasingly recognized as modulators of interconnected microbiome–host networks that extend beyond gastrointestinal function. This review synthesizes evidence on classical probiotic roles in maintaining gut homeostasis, immune regulation, and infection prevention, while integrating emerging systemic effects across the gut–brain, gut–skin, gut–oral, and metabolic axes. Rather than presenting isolated outcomes, we adopt a systems-level framework that links probiotic actions to shared mechanisms, including microbial metabolite signaling (e.g., SCFAs), competitive exclusion of pathobionts, barrier reinforcement, and immune–neuroendocrine pathway modulation. We further discuss translational advances that enable rational probiotic design, including targeted delivery platforms (encapsulation and protective matrices), engineered/next-generation strains, and postbiotic-inspired strategies, alongside sustainability considerations and regulatory/labeling challenges. Finally, we outline future directions emphasizing precision microbiome-centered interventions, synthetic biology, and AI-assisted multi-omics analysis to support strain- and context-specific probiotic strategies. Collectively, this review provides an integrated, systems-oriented synthesis to guide future research and accelerate safe clinical and industrial applications of probiotics. Full article

Mongolians have high overweight prevalence linked to their nomadic lifestyle and diet, but gut microbiota studies in this population are scarce. This study used fecal metagenomic and serum metabolomic analyses of 96 Mongolian participants (normal-weight n = 55, overweight n = 41) to characterize gut microbiome alterations and identify weight-related biomarkers. The analyses revealed that Parabacteroides distasonis, Barnesiella intestinihominis, and Alistipes onderdonkii were significantly reduced in overweight individuals (p < 0.05). Concurrently, the metabolites such as beta-cryptoxanthin, p-cresol, and ribothymidine were significantly down-regulated in the overweight group (p < 0.05). Random forest models from the three datasets showed a strong diagnostic ability for microbial families (AUC > 0.70). A subsequent integrated multi-kingdom classifier that combined microbiota and metabolite data achieved the highest performance (AUC = 0.818). Key features with high predictive contributions were identified, including Lactobacillus crispatus, Alistipes onderdonkii, and Parabacteroides distasonis, and metabolites, such as beta-cryptoxanthin, p-cresol, and picolinic acid. These results show the random forest model has high predictive value for distinguishing normal weight and overweight individuals. In summary, this study identified specific gut microbiota and serum metabolomic profiles linked to overweight in Mongolians. Multi-omics integration established a diagnostic biomarker model, laying a theoretical basis for microbiome-targeted weight management interventions. Full article

The human gut microbiota represents a complex and dynamic ecosystem of trillions of microorganisms that play a fundamental role in maintaining physiological homeostasis, regulating metabolism, and modulating the immune system. This narrative review explores the biochemical intricacies of the gut microbiome, focusing on the dominant phyla (Firmicutes, Bacteroidetes, Actinobacteria, Proteobacteria, Verrucomicrobia, Fusobacteria) and their specific contributions to host health. A critical emphasis is placed on the metabolic outputs of these microorganisms, such as short-chain fatty acids (SCFAs) like butyrate, which serve as vital energy sources and anti-inflammatory signaling molecules. Conversely, the review examines how dysbiosis, the disruption of microbial balance, is mechanistically linked to the pathogenesis of diverse conditions, including obesity, diabetes mellitus, inflammatory bowel disease (IBD), and gout. Furthermore, it highlights the profound impact of dietary interventions on microbial architecture, notably, how non-digestible carbohydrates promote beneficial taxa and eubiosis, while high-fat and high-sugar diets drive metabolic endotoxemia and systemic inflammation. By synthesizing current knowledge on microbial biotransformations of proteins and polyphenols, this work underscores the bidirectional relationship between nutrition and the microbiome. Ultimately, understanding these biochemical interactions is essential for developing targeted probiotic, prebiotic, and nutritional strategies to prevent and manage chronic metabolic and inflammatory disorders. Full article

Microbiome research is shifting from a focus on “whole microorganisms” to an emphasis on microbial functional components. This review systematically describes how the effects of microbial communities on the host are mediated by bioactive functional components released by microbes. These components primarily exert their effects through interactions with host Pattern Recognition Receptors (PRRs) and metabolic sensing receptors, thereby regulating host immune, metabolic, and barrier function networks. The biological effects of these functional components are highly context-dependent. Under homeostasis, metabolites such as SCFAs and bile acids promote mucosal immune tolerance and maintain epithelial barrier integrity. However, the same signals can become deleterious under dysbiosis, driving inflammation and contributing to colorectal tumorigenesis. Mechanistic dissection of individual components, such as lipopolysaccharide (LPS), is now propelling a transition in clinical translation from whole-microbe-based interventions toward component-oriented diagnostics and therapeutics. Component-oriented diagnostics and therapeutics use defined microbial molecules rather than whole microorganisms. Microbial nucleic acids (e.g., HPV DNA), metabolites (e.g., SCFAs), and proteins can serve as biomarkers for disease risk, diagnosis, and prognosis. Therapeutic strategies include targeted modulation of beneficial components, neutralization of harmful molecules, and engineered microbial delivery. Full article

Background: Subclinical psychological symptoms—such as low mood, perceived stress, and poor sleep—affect a large portion of the population and can impair quality of life despite remaining below clinical thresholds. The gut–brain axis has emerged as a promising target for interventions that support emotional and psychological resilience. Probiotics and postbiotics are gaining attention for their potential to modulate mood and stress via microbiome-related mechanisms, but human evidence remains limited, particularly in non-clinical populations. Objectives: We aimed to assess the effects of a two-strain combination of live microorganisms alongside a two-strain combination of heat-treated inactivated microorganisms on outcomes associated with anxiety, mood, perceived stress, and quality of life in healthy adults experiencing mild stress. Methods: This study was conducted in two parts. In Part I, a randomized, double-blind, placebo-controlled study, 100 participants were randomized to receive either a blend of live microorganisms (Bifidobacterium longum CECT 7347 and Lactobacillus rhamnosus CECT 8361) or an identical placebo once daily for 12 weeks. In Part II, a pilot feasibility study, a subset of eight placebo non-responders from Part I received the heat-inactivated preparation of the same bacterial strains in a 6-week trial extension phase. For Parts I and II, the primary outcome was the change in the Hamilton Anxiety Rating Scale (HAM-A). Secondary outcomes included measures of mood (Beck Depression Inventory (BDI); Patient Health Questionnaire-9 (PHQ-9)), stress (state and trait anxiety inventory (STAI); Perceived Stress Scale (PSS)), sleep (Pittsburgh Sleep Quality Index (PSQI)), quality of life (36-item Short Form Survey (SF-36)), gastrointestinal symptoms (Gastrointestinal Symptom Rating Scale (GSRS)), salivary cortisol and microbiome modulation. Results: In Part I, there were no significant effects of the live blend on the HAM-A, indicating that the primary endpoint was not met. In addition, no significant effects were seen on the STAI or PSS scores when compared to the placebo. However, participants consuming the live blend trended toward a reduction in total PHQ-9 scores compared to placebo (p = 0.089), whilst preliminary exploratory analyses suggested an improvement in anhedonia (p = 0.045). Furthermore, there was a significant improvement in the vitality domain of the SF-36 compared to placebo (p = 0.017). On microbiome analysis, it was noted that consumption of the live blend was linked to the preservation of butyrate-producing bacteria, particularly members of the Pseudoflavonifractor genus and the Clostridium SGB6179 species. Furthermore, the abundance of B. longum species was found to be inversely associated with the total PSS Scores. In Part II, supplementation with the inactivated preparation resulted in significant within-group improvements for the vitality (p = 0.006) and social functioning (p = 0.010) domains of the SF-36 and improvements in PSS scores compared to baseline (p = 0.050). Conclusions: Supplementation with either the dual-strain live or inactivated formulations was associated with significant improvements in the vitality domain of the SF-36, whilst participants receiving the inactivated formulation demonstrated lower perceived stress and improved social functioning compared to baseline. Overall, the findings from this pilot study suggest that these two biotic consortia are well-tolerated and may be associated with improvements in measures of vitality in individuals with subclinical psychological symptoms. The subtle observations detected for stress and anhedonia suggest that further well-powered trials are needed to better characterize these findings, potentially in populations with greater baseline symptomatology. Full article

Adolescence is a metabolically vulnerable period, during which rapid physiological maturation coincides with the dynamic remodelling of the gut microbiome. This narrative review summarises evidence from 2015 to 2025 to clarify how disturbances to the gut–liver axis driven by dysbiosis contribute to the development and progression of non-alcoholic fatty liver disease (NAFLD) in young people. Based on a systematic search of the databases PubMed, Scopus and Web of Science, we outline the basis of bidirectional communication between the gut and liver and emphasise how microbial imbalance alters the handling of lipids in the liver by enhancing de novo lipogenesis, impairing fatty acid oxidation and disrupting AMPK signalling and mitochondrial function. Consistent findings from clinical and experimental studies show that adolescents with NAFLD exhibit reduced microbial diversity, the enrichment of ethanol- and LPS-producing taxa, and altered short-chain fatty acid profiles. Each of these is associated with hepatic inflammation and metabolic reprogramming. Microbial molecules, including LPS, secondary bile acids and branched-chain amino acid metabolites, activate TLR4–NF-κB pathways, promote Kupffer cell activation and intensify oxidative stress. These mechanisms intersect with factors specific to adolescence, such as increased adiposity, hormonal shifts and diet-induced metabolic strain. Dietary patterns emerge as key modulators of these processes. Westernised diets promote dysbiosis and endotoxemia, whereas Mediterranean, fibre-rich and plant-based diets enhance SCFA production, strengthen epithelial integrity and modulate adiponectin-dependent hepatic metabolism. Micronutrient-sensitive epigenetic regulation, particularly that involving folate, choline and polyphenols, also plays a role in shaping lipid homeostasis and inflammatory tone. We also highlight emerging evidence that the activation of cytoprotective pathways, especially Nrf2, is dependent on lifestyle factors and links antioxidant-rich functional foods and physical activity to improved mitochondrial resilience and microbiome stability. We evaluate therapies targeting the microbiome, including probiotics, prebiotics, synbiotics and postbiotics, which reduce endotoxemia, restore microbial balance and complement dietary strategies. Thus, these findings emphasise the importance of age-specific, mechanistically informed interventions that integrate diet quality, microbial ecology, and the molecular pathways that govern metabolic health in adolescents with NAFLD. Full article

Introduction: Clostridioides difficile (C. difficile) is a major cause of antibiotic-associated diarrhea and healthcare-associated infections, with rising global incidence and severity due to the emergence of hypervirulent strains. Methods: This review synthesizes recent literature on the epidemiology, pathogenesis, diagnostic approaches, and therapeutic strategies related to C. difficile infection (CDI). Sources were selected from peer-reviewed journals, clinical guidelines, and emerging research between 2020 and 2025. Results: Advances in molecular diagnostics have improved the accuracy and speed of CDI detection. New therapeutic options such as fidaxomicin offer narrower-spectrum antibiotic activity with reduced recurrence rates. Fecal microbiota transplantation (FMT) has emerged as a highly effective option for recurrent CDI. Preventive efforts, including antibiotic stewardship programs and early-phase vaccine trials, show potential in reducing infection rates. Discussion: The management of CDI is evolving rapidly with the integration of precision diagnostics, targeted therapies, and microbiome-based interventions. Preventive strategies are critical, particularly in healthcare settings where C. difficile persists in the environment. Continued research and coordinated public health efforts are essential to reduce disease burden, improve outcomes, and limit transmission. Conclusions: Clostridioides difficile infections remain a major healthcare challenge with rising incidence and recurrent cases. Fidaxomicin has become the preferred first-line therapy. Microbiota-based therapies (like FMT, Rebyota, and Vowst) and Lipopolysaccharide Binding Protein (LBP) are highly effective for recurrent CDI prevention. Diagnostic strategies have improved with multi-step testing, enhancing accuracy and reducing overtreatment. Future focus lies in vaccines, targeted antimicrobials, and stricter prevention through antibiotic stewardship and hygiene. Full article

Metabolic diseases, including obesity, type 2 diabetes, and their related complications, have emerged as major global public health challenges. Increasing evidence indicates that gut microbiota dysbiosis contributes to disrupted metabolic homeostasis, chronic low-grade inflammation, and progression of metabolic disorders. Among candidate microbiome-based interventions, Lactiplantibacillus plantarum (L. plantarum) and Akkermansia muciniphila (A. muciniphila) have attracted particular attention because they regulate host metabolism through partially distinct yet potentially complementary mechanisms. L. plantarum has been associated with modulation of appetite-related hormones, adipose tissue remodeling, reinforcement of intestinal barrier function, and attenuation of inflammatory signaling. A. muciniphila has been linked to strengthening of the mucus barrier, production of beneficial metabolites, and improvement in immune and metabolic homeostasis. However, current evidence remains fragmented across strain-specific studies, heterogeneous formulations, and predominantly single-strain experimental designs, and direct comparative evidence for combined administration is still limited. This review synthesizes current epidemiological, mechanistic, preclinical, and clinical evidence on L. plantarum and A. muciniphila, with emphasis on their physiological traits, gut ecological adaptability, pathway-based metabolic effects, and translational challenges in obesity, type 2 diabetes, and related complications. We further highlight the ecological rationale for their functional complementarity and discuss priorities for future combination studies and precision implementation. Overall, the available literature supports functional complementarity and possible additive metabolic benefits, but synergistic effects in humans remain unconfirmed. A clearer understanding of strain identity, active therapeutic entities, delivery strategies, and host context will be essential for advancing this dual-target microbial strategy toward clinically meaningful applications. Full article

The skin serves as the first line barrier of innate immunity, protecting the body from external influences and maintaining its homeostasis. Exogenous and endogenous stress factors alter the structure and functional properties of the skin. The search for compounds capable of counteracting these processes has allowed the identification of peptides as promising ingredients of products for medicinal and cosmetic applications. This review comprehensively examines the mechanisms of action and dermatological applications of two distinct classes of natural products—endogenous human peptides and those derived from marine organisms. Human peptides exhibit numerous biological functions, including antimicrobial and immunomodulatory ones, as well as promoting antioxidant protection and wound healing. Microbiome-associated peptides are an underestimated but powerful regulator of skin aging through immunomodulation, inflammation control, barrier function maintenance, and selection of the proper microbial community. Peptides from marine organisms exhibit significant structural diversity and a broad spectrum of biological activity, including regenerative effects and effects on antibiotic-resistant microorganisms. This review summarizes current data obtained from in vitro, ex vivo, and clinical studies demonstrating a broad potential of peptides for maintaining skin health. Both peptide classes represent powerful, targeted strategies for innovative dermatological interventions aimed at promoting skin rejuvenation, protection, and overall homeostasis. Full article

Immune checkpoint inhibitors (ICIs) have revolutionized the therapeutic landscape for hepatocellular carcinoma (HCC); however, a considerable proportion of patients do not achieve durable clinical benefits. This highlights the need for reliable predictive biomarkers, which are currently lacking. The accumulated evidence supports a relevant role of the gut–liver axis in modulating immunotherapy outcomes, and several studies have identified distinct microbial features associated with either responders or non-responders. Responders to immunotherapy frequently present with higher microbial diversity and enrichment of beneficial taxa, whereas the expansion of pro-inflammatory and pathogenic bacteria has been associated with primary resistance and increased treatment-related toxicity in non-responders. However, the available findings remain heterogeneous across cohorts, likely owing to differences in geography, diet, liver disease etiology, treatment regimens, and microbiome analytical methods. Machine-learning models integrating metagenomic and metabolomic data have shown encouraging results in defining microbial signatures associated with treatment outcomes, although variability among cohorts currently limits their clinical applicability and generalizability. Beyond microbial taxonomic composition, microbiota-derived metabolites—such as short-chain fatty acids, bile acids, inosine, and tryptophan catabolites—appear to play a crucial role in shaping the tumor microenvironment and host immune responses, thus representing additional candidate biomarkers, also due to the relative ease of their measurement. Finally, microbiota-targeted interventions are emerging as potential strategies to enhance immunotherapy efficacy. Overall, the gut microbiome and its metabolic activity represent promising tools, albeit still under investigation, for patient stratification and personalized management in HCC treated with ICIs. Therefore, this review aims to summarize and critically discuss the current evidence on gut microbiota-derived biomarkers of response and resistance to ICIs in HCC, with particular focus on microbial composition, microbiota-related metabolites, and emerging microbiome-based therapeutic strategies. This narrative review provides an updated overview of the role of gut microbiota as both a biomarker and a therapeutic target in patients with hepatocellular carcinoma (HCC) receiving immune checkpoint inhibitor (ICI) therapy. Full article

Background: Alzheimer’s disease (AD) is a multifactorial neurodegenerative disorder characterized by amyloid-β aggregation, tau hyperphosphorylation, oxidative stress, and mitochondrial dysfunction. Emerging evidence indicates that the gut microbiota plays a critical role in modulating neuroinflammatory, and metabolic pathways involved in AD pathogenesis through the microbiota-gut-brain axis. Objective: This systematic review aims to comprehensively evaluate the role of the microbiota-gut-brain axis in Alzheimer’s disease, with a particular focus on its mechanistic links to oxidative stress, mitochondrial dysfunction, and amyloid pathology, as well as its therapeutic potential. Methodology: A comprehensive literature search was conducted using PubMed, Scopus, and Web of Science databases, focusing on studies evaluating gut microbiota composition, metabolomic changes, oxidative stress markers, mitochondrial activity, and therapeutic interventions in AD models and patients. Results: Altered gut microbial composition in AD is associated with increased pro-inflammatory taxa (Escherichia-Shigella, Bacteroides) and depletion of short-chain fatty acid (SCFA) producing bacteria (Faecalibacterium, Roseburia). Dysbiosis contributes to systemic inflammation, disrupted intestinal permeability, and microglial activation, leading to oxidative damage and mitochondrial impairment in neurons. Preclinical and clinical studies indicate that probiotics, prebiotics, and fecal microbiota transplantation can restore redox balance, reduce neuroinflammation, and improve cognitive outcomes. Multi-omics and AI-based models are emerging as tools for identifying microbiome-derived biomarkers for early AD detection. Conclusion: The gut microbiota-mitochondria-oxidative stress axis represents a promising therapeutic target in Alzheimer’s disease. Future research should focus on longitudinal human studies, standardized microbial profiling, and personalized microbiome-based interventions to translate these mechanistic insights into clinical benefit. Full article