Search Results (111)

Gut microbiota play a central role in shaping bile acid (BA) metabolism through community-specific capacities for deconjugation, dehydroxylation, and other transformation reactions. Distinct microbiome compositional patterns—often referred to as enterotype-like clusters—correspond to reproducible functional profiles that generate unique BA metabolic signatures with relevance for metabolic and gastrointestinal health. This narrative review synthesizes current evidence describing the interplay between microbial composition, BA metabolism, and metabolic dysfunction. A structured literature search was conducted in PubMed, Web of Science, EMBASE, and Scopus using predefined keywords related to bile acids, microbiome composition, metabolic disorders, and enterotypes. Studies were screened for human clinical relevance and mechanistic insights into BA–microbiome interactions. Across the evidence base, Bacteroides-, Prevotella-, and Ruminococcus-associated community types consistently demonstrate different BA transformation capacities that influence secondary BA production and downstream host signaling through FXR and TGR5. These differences are linked to variation in metabolic dysfunction-associated steatotic liver disease, obesity, type 2 diabetes, inflammatory bowel disease, and colorectal cancer. Host genetic variations in BA synthesis, transport, and signaling further modify these microbiome–BA interactions, contributing to the heterogeneity of dietary intervention responses. Overall, the literature supports a model in which microbiome-derived BA profiles act as metabolic phenotypes that shape host lipid and glucose homeostasis, inflammation, and gut–liver axis integrity. Emerging clinical applications include microbiome-stratified dietary strategies, targeted probiotics with defined BA-modifying functions, and therapeutic approaches that align BA-modulating interventions with an individual’s microbial metabolic capacity. Establishing integrated biomarker platforms combining microbiome clustering with BA profiling will be essential for advancing precision nutrition and personalized management of metabolic and gastrointestinal diseases. Full article

In animals and humans, nutrients influence signaling cascades, transcriptional programs, chromatin dynamics, and mitochondrial function, collectively shaping traits related to growth, immunity, reproduction, and stress resilience. This review synthesizes evidence supporting nutrient-mediated regulation of DNA methylation, histone modifications, non-coding RNAs, and mitochondrial biogenesis, and emphasizes their integration within metabolic and developmental pathways. Recent advances in epigenome-wide association studies (EWAS), single-cell multi-omics, and systems biology approaches have revealed how diet composition and timing can reprogram gene networks, sometimes across generations. Particular attention is given to central metabolic regulators (e.g., PPARs, mTOR) and to interactions among methyl donors, fatty acids, vitamins, and trace elements that maintain genomic stability and metabolic homeostasis. Nutrigenetic evidence further shows how genetic polymorphisms (SNPs) in loci such as IGF-1, MSTN, PPARs, and FASN alter nutrient responsiveness and influence traits like feed efficiency, body composition, and egg quality, information that can be exploited via marker-assisted or genomic selection. Mitochondrial DNA integrity and oxidative capacity are key determinants of feed conversion and energy efficiency, while dietary antioxidants and mitochondria-targeted nutrients help preserve bioenergetic function. The gut microbiome acts as a co-regulator of host gene expression through metabolite-mediated epigenetic effects, linking diet, microbial metabolites (e.g., SCFAs), and host genomic responses via the gut–liver axis. Emerging tools such as whole-genome and transcriptome sequencing, EWAS, integrated multi-omics, and CRISPR-based functional studies are transforming the field and enabling DNA-informed precision nutrition. Integrating genetic, epigenetic, and molecular data will enable genotype-specific feeding strategies, maternal and early-life programming, and predictive models that enhance productivity, health, and sustainability in poultry production. Translating these molecular insights into practice offers pathways to enhance animal welfare, reduce environmental impact, and shift nutrition from empirical feeding toward mechanistically informed precision approaches. Full article

For decades, cancer risk has been explained mainly by local factors. However, emerging evidence shows that the oral microbiome acts as a systemic modifier of oncogenesis well beyond the head and neck. This review synthesizes clinical and mechanistic data linking dysbiotic oral communities, especially Porphyromonas gingivalis, Fusobacterium nucleatum, and Treponema denticola, to malignancies across gastrointestinal, respiratory, hepatobiliary, pancreatic, breast, and urogenital systems. We summarize organ-specific associations from saliva, tissue, and stool studies, noting the recurrent enrichment of oral taxa in tumor and peri-tumoral niches of oral, esophageal, gastric, colorectal, lung, pancreatic, liver, bladder, cervical, and breast cancers. Convergent mechanisms include the following: (i) persistent inflammation (lypopolysacharide, gingipains, cytolysins, and collagenases); (ii) direct genotoxicity (acetaldehyde, nitrosation, and CDT); (iii) immune evasion/suppression (TLR/NLR signaling, MDSC recruitment, TAN/TAM polarization, and TIGIT/CEACAM1 checkpoints); and (iv) epigenetic/signaling rewiring (NF-κB, MAPK/ERK, PI3K/AKT, JAK/STAT, WNT/β-catenin, Notch, COX-2, and CpG hypermethylation). Plausible dissemination along an oral–gut–systemic axis, hematogenous, lymphatic, microaspiration, and direct mucosal transfer enables distal effects. While causality is not yet definitive, cumulative data support oral dysbiosis as a clinically relevant cofactor, motivating biomarker-based risk stratification, saliva/stool assays for early detection, and microbiome-targeted interventions (periodontal care, antimicrobials, probiotics, and microbiota modulation) alongside conventional cancer control. Full article

Bacterial metabolites play a dual role in hepatocellular carcinoma (HCC), exhibiting both tumor-promoting and tumor-suppressing activities dictated by their structural diversity. This review synthesizes recent advances in understanding how key microbial metabolites—such as bile acids, short-chain fatty acids, and polyamines—remodel the tumor immune microenvironment through mechanisms including immunometabolic reprogramming, epigenetic modification, and regulation of signaling pathways (e.g., FXR, TLR, and mTOR). We highlight their roles in modulating the function of T cells, NK cells, and tumor-associated macrophages and discuss emerging strategies that target these metabolites—including probiotic interventions, fecal microbiota transplantation, and metabolite-based adjuvants—to enhance immunotherapy efficacy and overcome resistance. By integrating mechanistic insight into translational potential, this work outlines a metabolite–immunometabolism–hepatocarcinogenesis framework and proposes novel combinatorial approaches for HCC treatment. Full article

Background: Periodontal dysbiosis contributes to liver injury through systemic inflammation, oral–gut microbial translocation, and endotoxemia. Lipopolysaccharides (LPSs) and virulence factors derived from periodontal pathogens, particularly Porphyromonas gingivalis (P. gingivalis) activate Toll-like receptor (TLR) signaling, trigger NF-κB-mediated cytokine release (e.g., TNF-α, IL-1β, IL-6), and promote oxidative stress and Kupffer cell activation within the liver. The present systematic review summarized clinical evidence supporting these mechanistic links between periodontal pathogens and hepatic outcomes, highlighting the role of microbial crosstalk in liver pathophysiology. Methods: A PRISMA-compliant systematic review was conducted by searching PubMed, Scopus, and the Cochrane library, as well as gray literature. Eligible study designs were observational studies and trials evaluating P. gingivalis and other periodontal pathogens (Aggregatibacter actinomycetemcomitans, Prevotella intermedia, and Tannerella forsythia) for liver phenotypes (Non-Alcoholic Fatty Liver Disease [NAFLD]/Metabolic Dysfunction-Associated Steatotic Liver Disease [MASLD], fibrosis/cirrhosis, acute alcoholic hepatitis [AAH], and Hepatocellular carcinoma [HCC]). Risk of bias was assessed using the Newcastle–Ottawa Scale adapted for cross-sectional studies (NOS-CS) for observational designs and the RoB 2 scale for single randomized controlled trials (RCTs). Due to the heterogeneity of exposures/outcomes, results were summarized narratively. Results: In total, twenty studies (2012–2025; ~34,000 participants) met the inclusion criteria. Population-level evidence was conflicting (no clear association between anti-P. gingivalis serology and NAFLD), while clinical cohorts more frequently linked periodontal exposure, particularly to P. gingivalis, to more advanced liver phenotypes, including fibrosis. Microbiome studies suggested stage-related changes in oral communities rather than the effect of a single pathogen, and direct translocation into ascitic fluid was not observed in decompensated cirrhosis. Signals from interventional and behavioral research (periodontal therapy; toothbrushing frequency) indicate a potential modifiability of liver indices. The overall methodological quality was moderate with substantial heterogeneity, precluding meta-analysis. Conclusions: Current evidence supports a biologically plausible oral–liver axis in which periodontal inflammation, often involving P. gingivalis, is associated with liver damage. Causality has not yet been proven; however, periodontal evaluation and treatment may represent a low-risk option in periodontitis-associated NAFLD. Well-designed, multicenter prospective studies and randomized trials with standardized periodontal and liver measurements are needed. Full article

Immune checkpoint inhibitors (ICIs) have radically changed the landscape of systemic treatment for hepatocellular carcinoma (HCC). Recently, there has been increasing interest regarding the relationship between the gut microbiome and the response to immunotherapy in oncological treatments. Among the gut commensals, Akkermansia (A.) muciniphila has gained increasing attention in the literature. A. muciniphila may affect the tumor microenvironment and enhance the efficacy of systemic therapies, including ICIs and targeted agents, by shaping host immune responses and metabolic pathways. This narrative review summarizes the current knowledge on A. muciniphila and its potential interaction with systemic therapies for HCC, focusing on its immunostimulatory properties, including enhancement of cytotoxic CD8⁺ T-cell activity and reversal of immunosuppressive tumor microenvironments. The therapeutic role of A. muciniphila might represent a novel and promising weapon in the HCC field, although the road is still long and the scientific evidence still remains in an exploratory stage. Its integration into clinical practice, however, requires robust clinical trials and a deeper understanding of its interactions within the gut–liver axis and tumor ecosystem. Full article

Cholangiocarcinoma (CCA) is an aggressive malignancy of the biliary tract with rising global incidence and limited treatment options. Its pathogenesis involves a complex interplay of genetic mutations, epigenetic dysregulation, inflammatory signaling, and environmental influences. Emerging evidence highlights the pivotal role of the gut–liver axis and microbiota dysbiosis in shaping biliary homeostasis and disease progression. Alterations in microbial composition disrupt apoptosis and autophagy, two key processes regulating cell survival and death, thereby contributing to tumorigenesis, metastasis, and therapy resistance. Specific taxa, including Enterococcus, Escherichia coli, Pseudomonas, Bifidobacterium, and Bacillus, demonstrate strain-dependent effects, acting either as tumor promoters through genotoxic metabolites and immune evasion or as potential tumor suppressors by inducing apoptosis and immune activation. These findings underscore the context-dependent roles of microbiota in CCA biology. Importantly, microbiota modulation offers novel therapeutic opportunities. Dietary interventions such as probiotics, prebiotics, and nutritional strategies, alongside innovative microbiome-targeted therapies, hold promise for restoring microbial balance, enhancing antitumor immunity, and improving patient outcomes. This review integrates current molecular and microbiological evidence to propose the gut microbiota as both a biomarker and a therapeutic target in CCA, opening avenues for precision medicine approaches in hepatobiliary oncology. Full article

Inter-organ communication plays a vital role in the pathogenesis of neurodegenerative diseases (ND), including Alzheimer’s disease (AD), Parkinson’s disease (PD), and Amyotrophic Lateral Sclerosis (ALS). Emerging research highlights the involvement of the gut–brain axis, immune system, and peripheral metabolic systems in modulating neuroinflammation, protein misfolding, and neuronal dysfunction by releasing cytokines, adipokines, growth factors, and other soluble factors, which in turn affect neuronal health and systemic inflammation. This review explores the complex bidirectional interactions between the brain and peripheral organs, including the gut, adipose tissue, liver, muscle, bone and immune system. Notably, the gut microbiome’s role in neurodegenerative diseases through the gut–brain axis, the impact of adipose tissue in inflammation and metabolic regulation, and the muscle–brain axis with its neuroprotective myokines are also discussed. Additionally, we examine the neuro-immune axis, which mediates inflammatory responses and exacerbates neurodegeneration, and liver–brain axis that is implicated in regulating neuroinflammation and promoting disease progression. Dysregulation of inter-organ pathways contributes to the systemic manifestations of neurodegenerative diseases, offering insights into both potential biomarkers and therapeutic targets, and, in turn, promising strategies for preventing, diagnosing, and treating neurodegenerative diseases. Full article

The expression “lung–gut–liver axis” refers to the interconnected processes occurring in the lungs, gastrointestinal tract, and liver, particularly in relation to immune function, microbial regulation, and metabolic responses. Over the past decade, growing concern has emerged regarding the detrimental impact of air pollution on liver disease. Air pollutants, including particulate matter (PM) and chemical gases such as nitrogen oxides (NOx), can influence the microbiome in the lungs and gut by generating reactive oxygen species (ROS), which induce oxidative stress and local inflammation. This redox imbalance leads to the production of altered secondary microbial metabolites, potentially disrupting both the alveolar–capillary and gut barriers. Under these conditions, microbes and their metabolites can translocate to the liver, triggering inflammation and contributing to liver diseases, particularly metabolic dysfunction-associated steatotic liver disease (MASLD), cirrhosis, and hepatocellular carcinoma (HCC). This manuscript aims to review recent findings on the impact of air pollution on liver disease pathogenesis, exploring the molecular, genetic, and microbiome-related mechanisms underlying lung–gut–liver interactions, providing insights into potential strategies to prevent or mitigate liver disease progression. Full article

Non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis (NASH) encompasses a spectrum of liver conditions and involves gut–liver axis crosstalk. We aimed to evaluate whether oral vancomycin modifies liver injury and the cecal microbiota in a methionine–choline-deficient (MCD) diet model of NASH. Male C57BL/6J mice (n = 28) were block-randomized to four groups (n = 7 each) for 10 weeks: standard diet (STD); MCD diet; STD + vancomycin (VANC); and MCD + VANC (2 mg/mouse ≈ 50 mg/kg, every 72 h). After 10 weeks, liver tissues were analyzed for histological changes, cytokine levels [interleukin-6 (IL-6), interleukin-8 (IL-8), transforming growth factor beta 1 (TGF-β1)], and immunohistochemical markers [ubiquitin and cytokeratin 18 (CK18)]. Cecal microbiota composition was evaluated with 16S ribosomal RNA (rRNA) sequencing. The MCD reproduced key NASH features (macrovesicular steatosis, lobular inflammation). Vancomycin shifted steatosis toward a microvesicular pattern and reduced hepatocyte injury: CK18 and ubiquitin immunoreactivity were decreased in MCD + VANC vs. MCD, and hepatic IL-8 and TGF-β1 levels were lower in MCD + VANC vs. STD. Taxonomically, STD mice had Lactobacillus-rich microbiota. The MCD diet alone reduced alpha diversity (α-diversity), modestly lowered Firmicutes and increased Desulfobacterota/Fusobacteriota. Vancomycin alone caused a much larger collapse in richness, depleting Gram-positive commensals and promoting blooms of Escherichia–Shigella, Klebsiella, Parabacteroides, and Akkermansia. In the MCD + VANC group, vancomycin profoundly remodeled the microbiota, eliminating key commensals (e.g., Lactobacillus) and enriching Desulfobacterota, Fusobacteriota, and Campylobacterota. Oral vancomycin in the MCD model of NASH improved liver injury markers and altered steatosis morphology, but concurrently reprogrammed the gut into a low-diversity, pathobiont-enriched ecosystem with near-loss of Lactobacillus. These findings highlight a therapeutic trade-off—hepatic benefit accompanied by microbiome cost—that should guide microbiota-targeted strategies for NAFLD/NASH. Full article

In humans, the bioactivity of polyphenols is highly dependent on dose intake and their interactions with the gastrointestinal tract and gut microbiota, which metabolize polyphenols into bioactive or inactive derivatives. Polyphenols are only partially absorbed in the small intestine, where enzymatic hydrolysis releases aglycone forms that may cross the gut barrier. A significant proportion of polyphenols escapes absorption and reaches the colon, where resident microbes convert them into simpler phenolic metabolites. Such molecules are often more bioavailable than the parent compounds and can enter systemic circulation, leading to distant effects. Although higher polyphenol consumption has been associated with preventive and therapeutic outcomes, even low intake or poor intestinal absorption may still confer benefits, as polyphenols in the colon can positively modulate gut microbiota composition and function, contributing to favorable shifts in the microbial metabolome. These interactions can influence host metabolic, immune, and neurological pathways, particularly through the gut–liver–brain axis. To provide a comprehensive understanding of these relationships, this review examines the dose-related activity of polyphenols, their microbiota-mediated biotransformation, their bioavailability, and the health effects of their metabolites, while also presenting a comparative overview of key studies in the field. We underscore the importance of integrating microbiome and polyphenol research to recapitulate and contextualize the health benefits of dietary polyphenols. Full article

Background: Breast cancer is the most common malignancy affecting women worldwide and continues to pose significant challenges despite progress in early detection and personalized therapies. While its pathogenesis has traditionally been associated with genetic, hormonal, and environmental factors, recent studies have highlighted the potential role of dysbiosis—an imbalance in gut and systemic microbiota—in breast cancer development and progression. This article aims to examine the mechanisms through which systemic dysbiosis may contribute to breast cancer risk and explore its therapeutic implications. Methods: This study seeks to analyze and compare the fecal microbiota profiles of breast cancer patients and healthy individuals from a single center in Craiova, Romania, in order to identify microbial signatures linked to breast cancer and BRCA mutation status. Special attention is given to the gut–liver axis and its influence on estrogen circulation, a key factor in hormone-sensitive breast cancers. Results: Evidence suggests that dysbiosis can influence breast cancer progression by promoting chronic inflammation, impairing immune regulation, and altering estrogen metabolism through the gut–liver axis. These effects may contribute to tumor development, immune evasion, and therapeutic resistance. Interventions aimed at restoring microbial balance show promise in preclinical studies for mitigating these effects. Conclusions: Systemic dysbiosis represents a potentially modifiable risk factor in breast cancer. Microbiota profiling may serve as a useful biomarker for risk stratification and therapeutic response. Future research into microbiome-based interventions could offer novel approaches for prevention and treatment in breast cancer care. Full article

This study investigated the beneficial effect of sea cucumber polysaccharides (SCP) on gut microbiota composition, metabolic profiles, and liver gene expression in mice. Using an integrative approach combining microbiome, metabolome, and transcriptome analyses, we demonstrated that SCP supplementation led to a marked rise in norank_f_Muribaculaceae levels and reduced the Firmicutes-to-Bacteroidota ratio. Metabolomic analysis revealed key alterations in amino acid and lipid metabolism, with L-arginine and 7-dehydrocholesterol identified as potential mediators of SCP’s beneficial effects. Transcriptomics revealed genes expression across nine metabolic pathways, with genes involved in steroid biosynthesis being upregulated, while those related to protein digestion and absorption were downregulated. Spearman’s correlation analysis highlighted strong associations between gut microbiota, lipid metabolism-related genes, and corresponding metabolites. Integration omics data further suggested that SCP primarily supports arginine biosynthesis through gut–liver axis crosstalk. These results provide an important basis for developing SCP-based functional food with prebiotic properties to support metabolic and liver health. Full article

Type 2 diabetes (T2D) is a complex metabolic disease characterized by chronic hyperglycemia due to insulin resistance and inadequate insulin secretion. Beyond the classically implicated organs, emerging evidence highlights the gut as a central player in T2D pathophysiology through its interactions with metabolic organs. The gut hosts trillions of microbes and enteroendocrine cells that influence inflammation, energy homeostasis, and hormone regulation. Disruptions in gut homeostasis (dysbiosis and increased permeability) have been linked to obesity, insulin resistance, and β-cell dysfunction, suggesting multifaceted “Gut-X axes” contribute to T2D development. We aimed to comprehensively review the evidence for gut-mediated crosstalk with the pancreas, endocrine system, liver, and kidneys in T2D. Key molecular mechanisms (incretins, bile acids, short-chain fatty acids, endotoxins, etc.) were examined to construct an integrated model of how gut-derived signals modulate metabolic and inflammatory pathways across organs. We also discuss clinical implications of targeting Gut-X axes and identify knowledge gaps and future research directions. A literature search (2015–2025) was conducted in PubMed, Scopus, and Web of Science, following PRISMA guidelines (Preferred Reporting Items for Systematic Reviews). Over 150 high-impact publications (original research and review articles from Nature, Cell, Gut, Diabetologia, Lancet Diabetes & Endocrinology, etc.) were screened. Data on gut microbiota, enteroendocrine hormones, inflammatory mediators, and organ-specific outcomes in T2D were extracted. The GRADE framework was used informally to prioritize high-quality evidence (e.g., human trials and meta-analyses) in formulating conclusions. T2D involves perturbations in multiple Gut-X axes. This review first outlines gut homeostasis and T2D pathogenesis, then dissects each axis: (1) Gut–Pancreas Axis: how incretin hormones (GLP-1 and GIP) and microbial metabolites affect insulin/glucagon secretion and β-cell health; (2) Gut–Endocrine Axis: enteroendocrine signals (e.g., PYY and ghrelin) and neural pathways that link the gut with appetite regulation, adipose tissue, and systemic metabolism; (3) Gut–Liver Axis: the role of microbiota-modified bile acids (FXR/TGR5 pathways) and bacterial endotoxins in non-alcoholic fatty liver disease (NAFLD) and hepatic insulin resistance; (4) Gut–Kidney Axis: how gut-derived toxins and nutrient handling intersect with diabetic kidney disease and how incretin-based and SGLT2 inhibitor therapies leverage gut–kidney communication. Shared mechanisms (microbial SCFAs improving insulin sensitivity, LPS driving inflammation via TLR4, and aryl hydrocarbon receptor ligands modulating immunity) are synthesized into a unified model. An integrated understanding of Gut-X axes reveals new opportunities for treating and preventing T2D. Modulating the gut microbiome and its metabolites (through diet, pharmaceuticals, or microbiota therapies) can improve glycemic control and ameliorate complications by simultaneously influencing pancreatic islet function, hepatic metabolism, and systemic inflammation. However, translating these insights into clinical practice requires addressing gaps with robust human studies. This review provides a state-of-the-art synthesis for researchers and clinicians, underlining the gut as a nexus for multi-organ metabolic regulation in T2D and a fertile target for next-generation therapies. Full article

Metabolic dysfunction-associated steatohepatitis (MASH) constitutes a significant and progressive liver disease, characterized by a complex pathogenesis that involves dysbiosis of the gut microbiota. While the multifaceted nature of MASH is widely recognized, its underlying mechanisms remain the subject of active investigation. Contemporary research highlights the critical role of the gut–liver axis, suggesting that disturbances in the gut microbiome may contribute to the progression of the disease. Probiotics have notably emerged as a promising therapeutic approach for MASH, with the potential to modulate the gut microbiome and mitigate symptoms. This review aims to examine the alterations in the gut microbiome associated with MASH pathogenesis, the interaction of probiotics with the gut–liver axis, and their significance in the development and management of MASH. By synthesizing current evidence on the mechanisms of action of probiotics, clinical trials, and comparative efficacy of different strains, as well as existing controversies, challenges, and future research directions, this review seeks to establish a scientific foundation for probiotic-based interventions as an innovative therapeutic strategy for MASH. Full article