Search Results (840)

Hypobaric hypoxia poses a serious threat to growth and development and can induce pronounced inflammatory responses. These effects are closely associated with the gut microbiota. However, the underlying mechanisms, particularly the role of gut microbiota in regulating hepatic metabolism under chronic hypoxic conditions, remain poorly understood. In this study, SD rats were used as recipients and assigned to three groups: a hypobaric hypoxia group (H), an antibiotic-treated group (HA), and an antibiotic-treated group receiving fecal microbiota transplantation from plateau zokors (HAM). All rats were maintained in a hypobaric hypoxia chamber simulating an altitude of 6000 m for 30 days. Subsequently, growth performance, routine hematological parameters, and multi-omics profiles were evaluated. Compared with the H group, both the HAM and HA groups showed significantly increased average daily gain (ADG) (p < 0.05), while the ADG/ADFI ratio was significantly higher in the HAM group than in the H group (p < 0.05). Monocyte count (Mon#) and monocyte percentage (Mon%) were significantly higher in the HA group than in both the H and HAM groups (p < 0.05). Microbiota analysis revealed significant enrichment of Lachnospiraceae_NK4A136_group in the HAM group, whereas Desulfovibrio was significantly enriched in the HA group (p < 0.05). Fecal metabolomics showed that ursodeoxycholic acid (UDCA) was significantly increased in the HAM group (p < 0.05). In the liver metabolome, the anti-inflammatory lipid FAHFA 18:1/20:3 was significantly elevated in the HAM group, whereas pro-inflammatory factors, including uric acid and leukotriene D4, were significantly reduced (p < 0.05). Correlation analysis further demonstrated that the abundance of Lachnospiraceae was positively correlated with FAHFA 18:1/20:3 and negatively correlated with uric acid and creatinine (p < 0.05). Collectively, these findings indicate that the gut microbiota can modulate gut–liver metabolism, alleviate inflammatory responses, and enhance the adaptation of rats to hypoxic environments. This study provides valuable insights into potential strategies for promoting sustainable animal health and adaptation under hypoxic conditions. Full article

Heart failure (HF) continues to be a major global health burden, with persistent morbidity and mortality despite guideline-directed and device-based therapies. Evidence suggests the gut–heart axis is a critical and underrecognized contributor to HF progression. Alterations in cardiac output and systemic venous congestion in HF lead to intestinal hypoperfusion, mucosal edema, and loss of barrier integrity, increasing intestinal permeability, gut dysbiosis, and translocation of microbial products. This systemic translocation is associated with chronic low-grade inflammation that activates innate immune pathways that correlate with endothelial dysfunction, oxidative stress, fibroblast activation, and adverse cardiac remodeling. Gut-derived metabolites derived by microbial metabolism modulate cardiovascular health by altering the metabolic profiles. Dysbiosis results in loss of protective short-chain fatty acid (SCFA)-producing bacteria and enriches pro-inflammatory taxa such as trimethylamine N-oxide (TMAO)-producing bacteria. Elevated TMAO is associated with increased mortality and hospitalization in HF, whereas SCFAs enhance barrier integrity and immune tolerance. Secondary bile acids and uremic toxins such as indoxyl sulfate and p-cresyl sulfate further link dysbiosis to fibrosis and vascular stiffness. Circulating markers such as TMAO, lipopolysaccharide-binding protein (LBP), and soluble CD14 carry prognostic value beyond traditional cardiac biomarkers. This review highlights current experimental, translational, and clinical evidence describing gut dysbiosis and its molecular links to HF progression. Targeting the gut–heart axis represents a novel therapeutic approach in HF. Dietary modulation, probiotics/prebiotics, fecal microbiota transplantation, and inhibitors of microbial metabolic pathways show promise. Future research should emphasize microbiota-based interventions in HF management. Full article

The gut microbiota is increasingly examined as a therapeutic target because it contributes to epithelial barrier integrity, microbial metabolite production, bile acid transformation, immune regulation, and communication between the gut and distant organs. This structured narrative review synthesizes evidence on microbiota involvement in metabolic, gastrointestinal, hepatic, cancer, and neuroimmune conditions, including MASLD/MASH, inflammatory bowel disease, irritable bowel syndrome, obesity, type 2 diabetes, hypertension, colorectal cancer, Parkinson’s disease, and autism spectrum disorder. Across these conditions, microbiome findings are biologically plausible but heterogeneous. Many associations are shaped by diet, geography, medication exposure, host genetics, disease stage, sampling methods, and analytical pipelines. Microbial alterations should therefore be interpreted as context-dependent signals and candidate modifiers rather than universal causal markers. Conventional microbiota targeted strategies include diet, physical activity, prebiotics, probiotics, synbiotics, postbiotics, and fecal microbiota transplantation. These approaches are clinically familiar, but their effects are often broad, host specific, strain dependent, and difficult to assign to one mechanism. Fecal microbiota transplantation has the clearest clinical role in recurrent Clostridioides difficile infection, while evidence for most other indications remains inconsistent. Engineered microbial therapeutics offer greater experimental precision through signal sensing, payload delivery, metabolic modulation, and genetic circuit design. However, most evidence remains preclinical or early translational. Progress requires stronger human trials, standardized methods, mechanistic validation, safety monitoring, ecological containment, transparent reporting, and proportionate regulation. Full article

Cockroaches display a double symbiosis: an obligate intracellular one with Blattabacterium spp., and a complex extracellular non-vertically transmitted gut microbiota, that may be affected by horizontally transmitted factors. Four experiments using 16S rRNA gene amplicon sequencing were conducted to analyze the microbiota of the hindgut and feces of adult cockroaches. They aimed to understand the influence of the environment and feces on the acquisition and development of the hindgut microbiota. We observed that sample type (hindgut vs. feces), rearing conditions (environment, i.e., place and diet), coprophagy, and host influenced microbiota composition. Cockroaches initially germ-free, placed in non-sterile conditions and with blocked parental coprophagy, were unable to develop the normal microbiota of the control population, demonstrating that coprophagy is essential for acquiring a normal microbiota. This also showed that, in the absence of parental fecal input, the cockroach gut microbiota is strongly diminished. Moreover, when exploring fecal microbiota differences among three cockroach species, the greatest divergence was observed between Periplaneta americana and Blattella germanica, with Blatta orientalis occupying an intermediate position. Therefore, P. americana was selected for fecal transplantation on B. germanica. This transplantation experiment indicates that different species select different gut microbes, and that even when they receive feces from other species, only some of those bacteria are retained. Overall, these results suggest that beyond other factors, the host species had the strongest influence on shaping the cockroach gut microbiota. Full article

High-altitude environments, characterized by hypoxia, low temperature, and intense ultraviolet radiation, profoundly disrupt host intestinal homeostasis and reshape the gut microbiota, thereby influencing immune regulation and acclimatization. This review systematically summarizes the dynamic compositional and functional changes in the gut microbiota in high-altitude natives, immigrant populations, short-term visitors, and relevant animal models. Current evidence indicates that long-term high-altitude adaptation is associated with directional microbial remodeling, including the enrichment of anaerobic and short-chain fatty acid (SCFA)-associated taxa, which may support energy metabolism and immune homeostasis. In contrast, acute high-altitude exposure more readily induces dysbiosis, impairs intestinal barrier integrity, and promotes the translocation of endotoxins and bioactive metabolites. Mechanistically, the gut microbiota and its metabolites participate in high-altitude adaptation and high-altitude-related disease pathogenesis by modulating barrier function, inflammatory responses, oxidative stress, and immune signaling, and by mediating interorgan communication—characterized by metabolite-driven systemic inflammation or tolerance—through the gut–lung, gut–heart, gut–brain, gut–kidney, and gut–testis axes. SCFAs, bile acids, amino acid-derived metabolites, and succinic acid may control immune homeostasis and inflammatory responses through pathways including TLR4/NF-κB and NLRP3. Although the causal relationships, core microbial effectors, and population-specific heterogeneity remain incompletely defined, microbiota-targeted interventions, including probiotics, prebiotics, and fecal microbiota transplantation, have shown promise for promoting acclimatization and preventing high-altitude-related disorders. Overall, this review provides an integrated framework linking environmental stress, gut microbial ecology, and host immune–metabolic adaptation at high altitude, and highlights future directions for mechanistic and translational research in high-altitude medicine. Full article

Emerging research highlights the complex interplay between the gut microbiome, skin health, and environmental exposures, forming what is now recognized as the gut–skin–exposome axis. This narrative review explores the role of gut microbiome dysbiosis—a disruption in the balance of intestinal microorganisms—in the pathogenesis and progression of various non-communicable inflammatory skin diseases, including acne, atopic dermatitis, psoriasis, rosacea, systemic lupus erythematosus, chronic spontaneous urticaria, hidradenitis suppurativa, and alopecia areata. This review synthesizes mechanistic studies, clinical trials, and Mendelian randomization data to elucidate how altered gut microbial composition contributes to systemic and cutaneous inflammation. Key modifiable factors, such as diet, antibiotics, stress, and sleep, as well as interventions like probiotics, prebiotics, synbiotics, and fecal microbiota transplantation, are discussed for their potential therapeutic value. By integrating clinical insights with microbiome science, this review underscores the importance of a holistic, systems-based approach in managing inflammatory skin diseases, offering clinicians evidence-based strategies to improve patient outcomes through gut microbiome modulation. Full article

Research on autism spectrum disorders (ASDs) has so far focused primarily on the gut–brain axis, whereas the role of the gut–liver axis remains insufficiently explored. The aim of this study was to evaluate whether microbiota derived from girls with ASD induces dysbiotic changes in gut microbiota composition and leads to alterations in gut–liver axis processes in pseudo-germ-free (PGF) BALB/c mice. We also examined whether these processes could be modulated by altering the gut microbiota using the probiotic strains Lactiplantibacillus plantarum CCM 7512 and Limosilactobacillus reuteri CCM 8617 in combination with ground flaxseed (Linum usitatissimum L.) as a source of omega-3 polyunsaturated fatty acids and fermentable fiber. Colonization with fecal microbiota derived from girls with ASD resulted in dysbiotic changes in the composition of the cecal microbiota, characterized by an increased relative abundance of Escherichia–Shigella, Fusobacterium, Alistipes, and the Ruminococcus gnavus group. These changes were accompanied by impaired intestinal mucosal integrity, altered metabolomic pathways related mainly to aromatic amino acids and lipid metabolism, increased hepatic immunoreactivity of iNOS and COX-2, and elevated activity of the liver-specific LDH-5 isoenzyme. These results suggest that synbiotic intervention contributed to remodeling of the cecal microbiota composition, restoration of intestinal epithelial integrity, and modulation of metabolomic pathways, which was reflected by reduced immunoreactivity of iNOS and COX-2 in liver tissue and decreased activity of the LDH-5 isoenzyme. These findings support the role of microbiota-mediated metabolic processes in communication between the gut and the liver within the gut–liver axis. Full article

The gut microbiome plays a key role in the pathogenesis of cardiovascular disease through systemic inflammation, impaired lipid metabolism, and proatherogenic gut metabolites like trimethylamine N-oxide. Gut dysbiosis contributes to decreased level of microbial metabolites such as short-chain fatty acids, bile acids, coprostanol, and phenylacetylglutamine, as well as increased intestinal permeability and platelet hyper-reactivity, and exacerbating cardiovascular risk. New microbiome-focused treatments such as probiotics, prebiotics, synbiotics, and fecal microbiota transplantation are showing potential to help reduce cardiovascular diseases. However, bringing these therapies into clinical settings is difficult because they vary by strain and individual response. The gut–heart connection offers an innovative approach to preventing and treating heart condition, but additional research is needed to ensure lasting effectiveness and safety. Full article

Fecal microbiota transplantation (FMT) has emerged as a microbiota-directed therapeutic strategy with established efficacy in recurrent Clostridioides difficile infection (rCDI) and expanding investigational applications in pediatric medicine. Given the central role of the gut microbiota in immune maturation, metabolic homeostasis, and colonization resistance—particularly during early life—restoring microbial diversity represents a biologically plausible intervention for disorders characterized by dysbiosis. This narrative review critically examines current evidence regarding the indications, efficacy, safety, and practical considerations of FMT in pediatric populations. A structured literature search was conducted across PubMed/MEDLINE, Scopus, Web of Science, and the Cochrane Library from inception through December 2025. Eligible studies included randomized controlled trials, observational studies, systematic reviews, meta-analyses, and guideline statements addressing pediatric FMT. RCDI remains the primary and best-supported indication, with reported success rates exceeding 80% after a single FMT and approaching 90% with repeat procedures. Evidence for other indications—including inflammatory bowel disease (IBD), malignancy-associated CDI, transplant recipients, multidrug-resistant organism (MDRO) decolonization, neurodevelopmental disorders, allergic colitis, and functional gastrointestinal disorders—remains limited and heterogeneous. While short-term remission rates in pediatric ulcerative colitis appear promising, data derive largely from small, non-standardized studies, and long-term efficacy and safety remain insufficiently defined. FMT usage in immunocompromised children, particularly oncology and transplant populations, is controversial due to limited pediatric-specific evidence and theoretical risks. Substantial variability in donor screening, preparation methods, dosing, and administration routes further limits standardization. Currently, FMT should be considered established therapy for pediatric rCDI, whereas other applications require well-designed, multicenter trials with long-term follow-up to clarify safety and clinical benefit. Full article

Background: Ketamine is a rapid-acting antidepressant for major depressive disorder; however, its effects are short-lasting and associated with neurotoxic side effects. Thus, identifying strategies to prolong its antidepressant effects is of critical importance. It has been shown that Dajianzhong Decoction (DJZT) prolongs the antidepressant effects of ketamine through modulation of the gut microbiota, but the underlying mechanisms remain unclear. Method: Fecal microbiota transplantation, metabolomic profiling, pharmacological interventions, and behavioral approaches were employed together with a chronic unpredictable mild stress (CUMS) mouse model to investigate how microbiota-derived signals mediate the combined effects of DJZT and ketamine. Results: Microbiota from CUMS mice induced depressive-like behaviors in recipient mice, accompanied by reduced levels of short-chain fatty acids (SCFAs), decreased FFAR2 expression in the medial prefrontal cortex, and increased neuroinflammation and synaptic deficits. These alterations were reversed by microbiota from DJZT-plus-ketamine-treated donors. Notably, acetic acid and isobutyric acid were identified as key SCFAs restored by the combined treatment and were significantly associated with behavioral outcomes. Moreover, SCFA supplementation recapitulated these effects by activating FFAR2 and suppressing NLRP3–IL-1β signaling. Importantly, pharmacological inhibition of FFAR2 using GLPG0974 abolished the antidepressant-like, anti-inflammatory, and synaptic protective effects of the microbiota from DJZT-plus-ketamine-treated donors. Conclusions: These findings demonstrate that microbiota-derived SCFAs mediate the synergistic antidepressant effects of DJZT and ketamine via a central FFAR2-dependent mechanism involving suppression of neuroinflammation. This work highlights a potential role of the SCFA–FFAR2–NLRP3– IL-1β axis in influencing ketamine efficacy and points to microbiota-modulating strategies as a possible avenue for improving antidepressant therapy. Full article

Metabolic dysfunction-associated steatotic liver disease (MASLD) is a highly prevalent liver-centred manifestation of systemic metabolic dysfunction. The gut–liver axis provides a biologically credible therapeutic rationale because intestinal dysbiosis, impaired barrier integrity, microbial metabolites, bile acid signalling, short-chain fatty acids, and trimethylamine N-oxide may influence hepatic steatosis, inflammation, and fibrogenesis. This narrative review critically evaluates dietary patterns, prebiotics, probiotics, synbiotics, postbiotics, and fecal microbiota transplantation (FMT) as microbiome-directed strategies in MASLD. The comparative framework prioritises disease-specific human evidence, clinically meaningful endpoints, trial duration and sample size, reproducibility, safety, and feasibility. Dietary optimisation remains the most clinically grounded intervention, whereas probiotics and synbiotics show modest and heterogeneous signals on biochemical or metabolic surrogate endpoints. Prebiotics are mechanistically coherent but supported by limited liver-centred trials. Postbiotics and microbiome-mediated bioactives remain early-stage and require stricter definitional boundaries. FMT is investigational and should not be extrapolated from its established role in recurrent Clostridioides difficile infection. Most available evidence across all intervention categories relies principally on surrogate endpoints—including aminotransferases, insulin resistance indices, lipid parameters, and microbiome compositional shifts—rather than on validated liver-centred outcomes such as histological improvement or quantitative liver fat assessment; this constrains the strength of conclusions that can currently be drawn. Across all categories, microbiome modulation does not by itself establish liver disease modification, and no microbiome-targeted nutritional intervention has yet demonstrated histological benefit in MASLD. Future trials in this field should prioritise validated hepatic endpoints, phenotype-stratified patient enrolment, adequate follow-up duration, and direct comparisons between intervention categories to determine which microbiome-directed strategies, if any, deliver measurable and reproducible hepatic benefit beyond surrogate markers. Full article

Antimicrobial resistance (AMR) constitutes a critical and escalating global public health challenge, severely limiting the potential of existing antimicrobial drugs and escalating infection-associated morbidity and mortality rates. This analysis focuses on the ESKAPE pathogens (Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacter species), which are prioritized by the World Health Organization (WHO) and represent a significant cause of nosocomial infections due to their extensive drug resistance. We provide an in-depth review of the global prevalence and specific antibiotic-resistant mechanisms of these pathogens. Due to the decline in the traditional antibiotic development pipeline, accelerated development of alternative therapeutic strategies is essential. The review comprehensively discusses innovative non-traditional therapies currently being explored to bypass traditional antibiotic limitations, such as phage therapy, antimicrobial peptides (AMPs), anti-virulence therapies, fecal microbiota transplantation (FMT), and targeted CRISPR-based approaches. Addressing the ESKAPE challenge requires a concerted, multi-sectoral strategy guided by the One Health principle, focusing on enhancing public awareness, improving surveillance and research, optimizing judicious antibiotic use, and cultivating sustainable investment in novel interventions. Full article

The gut microbiota regulates host physiology and drives extraintestinal diseases through the gut–X axis. Bile acids (BAs) function as key mediators of this interorgan crosstalk by activating nuclear and membrane receptors (FXR, TGR5, PXR, VDR). Traditional Chinese Medicine (TCM) demonstrates efficacy across multiple organ systems through multi-component formulations. This narrative review synthesizes evidence from preclinical and clinical studies supporting that TCM exerts systemic protection via strategic modulation of the microbiota–BA–host receptor axis, which functions as a core regulatory circuit within a larger network of microbial metabolites. Mechanistically, representative TCM formulas remodel gut microbial ecology and reinforce intestinal barrier integrity, leading to optimized BA profiles. These favorable BA signatures engage tissue-specific receptor signaling to resolve inflammation, mitigate fibrosis, and restore metabolic homeostasis across the gut–heart, gut–kidney, gut–liver, gut–bone, and gut–endocrine axes. Support for this causal relationship is provided by microbiota depletion, fecal transplantation, and multi-omics studies, collectively suggesting that TCM’s benefits are microbiota-dependent and at least partially BA-mediated. Moreover, context-dependent modulation of BA receptors, such as differential regulation of FXR, enables TCM to achieve pathology-specific outcomes. Current evidence is derived predominantly from preclinical models, and clinical data remain lacking. Nonetheless, the microbiota–BA–organ axis thus provides a potential framework for understanding TCM’s systemic actions and establishes a molecular basis for developing microbiome-informed precision therapeutics. Future directions include patient stratification and precision intervention design inspired by TCM’s ecological modulation strategies. Full article

The human gut microbiome is essential for immune regulation and mucosal homeostasis, functions that are profoundly disrupted during HIV infection. Early viral replication in the gut-associated lymphoid tissue (GALT) triggers a self-reinforcing cycle of CD4⁺ T-cell depletion, epithelial barrier breakdown, and increased microbial translocation. This persistent immune activation continues even under effective antiretroviral therapy (ART). A growing body of evidence indicates that HIV infection is consistently associated with alterations in gut microbial communities. This dysbiosis is typically characterized by fewer beneficial butyrate-producing commensal bacteria and an enrichment of pro-inflammatory microbial taxa. It also involves disturbances in key microbial metabolites, including short-chain fatty acids (SCFAs) and tryptophan catabolites. Such changes not only exacerbate systemic inflammation but may also contribute to incomplete immune reconstitution and the persistence of latent viral reservoirs despite long-term ART. In this review, we summarize current knowledge of microbiome–HIV interactions, with particular emphasis on the mechanisms through which gut dysbiosis contributes to immune dysfunction and viral persistence. We discuss recent advances in multi-omics technologies, as well as experimental systems such as gnotobiotic and humanized mouse models and intestinal organoid platforms that are helping to elucidate these complex interactions. Furthermore, we evaluate emerging microbiome-targeted interventions—including probiotics, prebiotics, fecal microbiota transplantation, and engineered bacterial therapeutics—and consider their potential role as adjunctive strategies in HIV treatment and cure research. By integrating microbiological, immunological, and clinical perspectives, this review highlights key knowledge gaps and outlines future research directions aimed at harnessing the gut microbiome as a novel therapeutic avenue in HIV management and eradication. Full article

The gut microbiota has emerged as a key regulator of cardiovascular health, influencing metabolic, inflammatory, and vascular pathways. Growing evidence indicates that gut dysbiosis, characterized by reduced microbial diversity, depletion of beneficial short-chain fatty acid–producing bacteria, and enrichment of pro-inflammatory taxa, is associated with major cardiovascular risk factors and disease progression. Microbial-derived metabolites, including trimethylamine/trimethylamine N-oxide, short-chain fatty acids, amino acids and bile acids, may play a central role in modulating lipid metabolism, endothelial function, inflammation, and thrombosis, although the underlying mechanisms remain incompletely understood. Recent multi-omics approaches have expanded this understanding by identifying personalized microbiome–metabolome signatures linked to cardiovascular risk, supporting a shift toward precision medicine. In this review, we summarize current evidence on the composition and functional role of the gut microbiota in cardiovascular disease and critically discuss emerging microbiota-targeted strategies. These include dietary interventions, prebiotics, probiotics, synbiotics, antibiotics, enzyme inhibitors, and fecal microbiota transplantation, which may contribute to both the prevention and adjunctive treatment of cardiovascular conditions. In addition, we address the challenges of integrating gut microbiota management into clinical practice and highlight the importance of tailored strategies, including exercise-based interventions, microbial enzyme inhibitors, and postbiotics. Despite promising preclinical and early clinical data, the translation of microbiome-based therapies into routine practice remains limited by heterogeneity in study design, the lack of standardized protocols, and incomplete mechanistic understanding. Overall, targeting the gut microbiota represents a novel and potentially complementary approach for cardiovascular disease prevention and management, warranting further well-designed clinical studies. Full article