搜索结果：Gut microbes

Previous observational study findings have indicated a vital association between gut microbiota features and retinal diseases based on the "gut-retina" axis. However, whether their relationships underlie causal effects remains to be established. Instrumental variables of 211 gut microbiota taxa were obtained from a genome-wide association study (GWAS), and 28 gut-associated metabolites and pathways were included as exposures. A two-sample Mendelian randomization (MR) study was carried out to estimate gut microbiota effects on diabetic retinopathy (DR), early age-related macular degeneration (eAMD), retinal detachments and breaks (RDs/RBs), retinal vascular occlusion (RVO), disorders of the choroid and retina (D-C/R), and visual impairment. MR methods, including inverse variance weighted (IVW), MR‒Egger, weighted median, simple mode, and weighted mode methods, were used to investigate the causal relationship between gut microbiota features and various outcomes. Heterogeneity, pleiotropy, and stability tests of MR results were performed, and Bonferroni's correction was used to test the strength of the causal relationships between exposures and outcomes, as well as reverse and multivariable MR analyses. Through MR analysis of 211 microbes and six clinical phenotypes, a total of 35 gut microbiome and 3 associated metabolites were found to be associated with various outcomes. Cochrane's Q test revealed that there was no significant heterogeneity between various single-nucleotide polymorphisms. In addition, no significant level of pleiotropy was found according to the MR‒Egger and MR-PRESSO global tests. After the Bonferroni-corrected test, Genus id.2041 (OR = 0.874, 95% CI: 0.816-0.936, p = 1.10e - 04, IVW) showed robust causality with D-C/R, which had a nominal association with multiple other retinal diseases as well. Seven exposure-outcome effects markedly remained valid when BMI or alcohol intake frequency was separately included in multivariable MR analyses. According to the results of reverse MR analysis, no significant causal effect of outcomes was found on gut microbiota. No significant heterogeneity of instrumental variables or horizontal pleiotropy was found. We confirmed a potential causal relationship between some gut microbiota features and retinal diseases, thus providing new insights into the gut microbiota-mediated mechanism of retinopathy and indicating vital biomarkers for potential diagnostic, therapeutic, and prevention strategies.

The human gut microbiome comprises a diverse community of bacteria whose interactions with the host range from beneficial mutualism to opportunistic pathogenicity. These interactions are shaped by genomic plasticity and ecological pressures that influence whether microbes support host health, remain conditionally harmless, or contribute to disease. Understanding the mechanisms underlying these shifts is essential for clarifying the balance between cooperation and pathogenicity within the gut ecosystem. This review explores the genomic and evolutionary mechanisms that shape microbial adaptation across the mutualism-pathogenicity spectrum in the human gut. Key processes, including horizontal gene transfer (HGT), host-mediated selection, and niche specialization, enable microbes to acquire, regulate, or retain traits that influence colonization, metabolic function, and virulence. These adaptive mechanisms allow gut bacteria to respond dynamically to ecological pressures such as inflammation, antibiotic exposure, and dietary change, resulting in context-dependent microbial behaviors. The review also considers how concepts from insect endosymbiosis may provide insight into gut microbial adaptation. While both systems exhibit host specialization, major differences in transmission mode, ecological flexibility, and genome evolution limit direct comparisons. Rather than following a fixed progression toward parasitism, gut microbes exhibit flexible adaptive strategies shaped by host and environmental conditions. By integrating ecological and evolutionary perspectives, this review presents a balanced framework for understanding how genomic adaptation influences microbial behavior in the gut. This perspective improves our understanding of dysbiosis and microbial pathogenesis and may support the development of microbiome-informed therapeutic strategies for maintaining host health.

Researchers now see aging as a process shaped by the interactions among metabolism, epigenetics, and hormones. Recent studies suggest that gut microbes play an important role in this system by making metabolites that can affect gene expression and chromatin structure. Still, it is not fully clear how gut microbes and the body influence each other as we age, since both are constantly changing. This review brings together current research on how metabolites from gut microbes-such as short-chain fatty acids, bile acids, tryptophan derivatives, and polyamines-affect the body's epigenetic machinery through processes such as DNA methylation, histone modifications, and chromatin remodeling. We examine evidence from cell studies, animal experiments, and human research to assess the strength of the links and distinguish direct effects on chromatin from indirect metabolic or gene-expression changes. We focus especially on endocrine and reproductive organs, such as the hypothalamus, pancreas, liver, fat tissue, and cells that support the gonads, where signals from gut microbes overlap with hormonal control and metabolism. In these tissues, microbial metabolites influence key pathways related to inflammation, mitochondria, and nutrient sensing, but there is still little direct evidence in humans. The review also points out differences between lab models and what is observed in patients, highlighting the need for further work to apply these findings in real-world settings. Interactions between gut microbes and epigenetics form a two-way link between metabolism, immunity, and aging of the endocrine system. While more evidence shows that microbial metabolites can shape gene activity and epigenetic patterns, most of what we know comes from animal studies rather than direct tests in people. Moving forward, researchers will need to use broad, long-term studies that combine different types of data to figure out cause and effect and which tissues are involved. Understanding this system better could help create new biomarkers and treatments to influence aging by targeting the microbiome and its effects on epigenetics.

Carpenter bees of the genus Xylocopa interact extensively with woody substrates during nest construction, suggesting that associated microorganisms may contribute to the degradation of plant-derived polymers. Despite their ecological relevance, the gut microbiome and functional potential of Xylocopa species remain poorly characterized. In this study, we investigated the bacterial and fungal gut microbiome of Xylocopa frontalis using 16S rRNA and ITS amplicon sequencing, complemented by culture-dependent approaches. The gut microbiome was dominated by bacterial taxa commonly associated with bees, including Bombiscardovia, Bifidobacterium, and Frischella, whereas fungal communities were more variable and included genera such as Aspergillus and Cladosporium. Several taxa were consistently detected across samples, indicating recurrent community members; however, a consistent core microbiome was not clearly observed. We established a collection of cultivable microorganisms, including a bacterial isolate capable of utilizing cellulose as a carbon source, as demonstrated by plate assays. Phylogenetic and genomic analyses identified this isolate as Bacillus velezensis strain Xf, which harbors genes associated with cellulose and hemicellulose degradation. These findings suggest the potential for lignocellulose-related metabolism in the gut microbiome. Together, our results provide a combined culture-independent and culture-dependent characterization of the X. frontalis gut microbiome and identify microorganisms with relevant functional traits. Although based on a limited sample size, this study expands current knowledge of microbial associations in carpenter bees and establishes a foundation for future investigations into their functional roles. KEY POINTS: • Gut microbiome of Xylocopa frontalis was characterized by amplicon sequencing • Bacillus velezensis strain Xf showed cellulolytic activity in vitro • Gut-associated microbes showed genes linked to lignocellulose degradation.

The grape berry moth (GBM) Paralobesia viteana (Lepidoptera: Tortricidae) is an important pest of grapes in eastern North America. The larvae damage grape clusters by direct feeding and by increasing susceptibility to fungal and bacterial pathogens. In this study, we sequenced the V3-V4 region of the 16S rRNA gene and the V4 region of the 18S rRNA gene to characterize the composition and diversity of GBM larval gut bacterial and fungal communities when fed on immature and mature 'Concord' grapes. The data were analysed with QIIME 2, and downstream analyses included taxonomic composition, differential abundance, phylogenetic, functional and alpha/beta diversity analyses. While overall bacterial community diversity did not differ significantly between treatments, differential abundance analysis identified specific bacterial taxa enriched in each larval group. Ninety-three per cent of the bacterial communities belonged to the phylum Proteobacteria, and some may play roles in amino acid and carbohydrate metabolism in the insect gut. Analyses of the 18S rRNA region showed significant taxon-level compositional differences in fungal communities between larvae grown on grapes at different ripening stages. Ascomycota was the dominant phylum (98%) present in the guts of larvae fed on mature grapes, while larvae fed on immature grapes mainly contained fungi within the Cryptomycota (51%). Larvae fed on ripe grapes had a 10-fold higher fungal abundance and were enriched in Saccharomycetales yeasts. Several of the identified microbial taxa in larval guts are commonly found in grapes, which suggests they might be transient insect residents that are ingested with the diet. In conclusion, diet strongly shaped GBM gut-associated fungal communities; specific bacterial taxa also differed between larval groups despite similar overall bacterial diversity. These results contribute to basic knowledge of gut-associated microbes in fruit-feeding insects.

The use of titanium dioxide (TiO2) as a food additive has persistently elicited concerns about its potential toxicity, primarily attributed to the significant presence of nanoparticles. Studies have recently demonstrated that nano- or micro-sized food-grade TiO2 (fg-TiO2) particles can disrupt gut microbial balance and weaken the intestinal barrier; however, the underlying mechanisms remain poorly understood. Furthermore, research on dietary interventions for repairing fg-TiO2-induced intestinal injury is limited. This study delved into the role of the interactions among gut microbes, indole-3-lactic acid (ILA) and mucin sulfation in fg-TiO2-induced intestinal mucosal barrier damage through multi-omics analysis, and revealed the protective effects of quercetin. Prolonged oral administration of fg-TiO2 at doses pertinent to human exposure resulted in notable intestinal inflammation and mucosal barrier damage through diminishing mucin sulfation. Further analysis demonstrated that fg-TiO2 caused significant gut microbiota dysbiosis and metabolite changes. It was found that Lactobacillus and its metabolite ILA, an aryl hydrocarbon receptor (AHR) agonist, was significantly downregulated following oral ingestion of fg-TiO2, which decreased the activation of AHR and ultimately led to a loss in mucin sulfation in colon tissues. Notably, experiments involving fecal microbiota transplantation (FMT) and ILA supplementation indicated gut microbial shifts and the consequent decrease in colonic ILA levels were accountable for the detrimental effects of fg-TiO2 on mucin sulfation and intestinal barrier integrity. Moreover, this study found that dietary intervention with quercetin could effectively reverse the damage to the intestinal mucosal barrier induced by fg-TiO2 through targeting gut microbiota-ILA-mucin sulfation axis. This research uncovered the adverse impacts of fg-TiO2 on gut homeostasis and indicates the potential of quercetin to combat the intestinal toxicity of fg-TiO2. These findings enhanced our comprehension of the safety profile of fg-TiO2 and proposed a nutritional approach to mitigate the health risks associated with fg-TiO2 exposure.

Polycystic Ovary Syndrome (PCOS) is a prevalent endocrine and metabolic disorder among reproductive-age women, in which emerging evidence suggests a substantial role played by the gut microbiota. To comprehensively evaluate gut microbiota alterations in PCOS and identify microbial biomarkers through integrated analysis, a systematic search of PubMed, Web of Science, and Embase was conducted for studies employing 16S rRNA gene sequencing of fecal samples from PCOS cohorts. Ten eligible PCOS cohorts, comprising 858 individuals, were included in the study, from which a risk score was derived using a 20-gene gut microbial signature associated with PCOS. Meta-analysis at the genus level identified that Subdoligranulum, NK4A214_group, and Collinsella significantly decreased, and Bacteroides increased in PCOS across multiple cohorts. Machine learning analysis identified a 20-genus microbial signature using the least absolute shrinkage and selection operator (LASSO) method, which was used to construct a risk score with an AUC of 0.835 in diagnosis prediction. Network analysis further identified Negativibacillus and Lachnospiraceae_UCG_010 as potential driver microbes in PCOS. The analysis in this study highlights key alterations in the gut microbiota across PCOS cohorts. The identified gut microbial signature and derived LASSO-based risk model offer novel insights and a potential tool for PCOS diagnosis.

Alzheimer's disease (AD) is the most common form of dementia, driven by complex interactions among aging-related biological changes, neuronal degeneration, mitochondrial dysfunction, and environmental factors. Despite extensive research, effective disease-modifying therapies remain unavailable. Increasing evidence highlights the gut-brain axis as an important contributor to AD pathogenesis, particularly through amyloid-producing gut microbes that promote immune activation, neuroinflammation, and cerebral amyloid accumulation. This review summarizes current evidence linking gut microbiota (GM) dysbiosis to AD, focusing on microbial metabolites, neuroinflammatory pathways, and microbiota-targeted therapeutic strategies. A systematic analysis of experimental and clinical studies reveals that altered gut microbial composition is associated with systemic and neuroinflammation, blood-brain barrier dysfunction, oxidative stress, and neuronal damage. Key microbial metabolites, including short-chain fatty acids and indole derivatives, exhibit neuroprotective effects by regulating immune responses, maintaining barrier integrity, and supporting neuronal energy metabolism; disruption of these metabolites may accelerate neurodegeneration. Microbiota-based interventions such as probiotics, prebiotics, dietary modification, and fecal microbiota transplantation show beneficial effects in preclinical models by restoring microbial balance and reducing neuropathological features, although clinical evidence in humans remains limited. Overall, current findings support a contributory role of gut dysbiosis in AD and suggest that targeting the GM may offer a promising complementary strategy for disease modification and future therapeutic development.

CRC remains a major cause of cancer-related morbidity and mortality worldwide. In recent years, the gut microbiota has gained increasing attention in CRC research. Intestinal microbes are not passive bystanders in tumor development. They may promote persistent inflammation, disrupt epithelial barrier integrity, alter microbial metabolites, and affect host immune and signaling pathways. Emerging evidence also suggests that microbiota-related metabolites and microbial functional alterations may influence host epigenetic regulation, including DNA methylation and chromatin-associated signaling, thereby further shaping colorectal carcinogenesis. Together, these changes can create a microenvironment that favors tumor initiation and progression. Several bacterial species, including Fusobacterium nucleatum, Parvimonas micra, and Peptostreptococcus anaerobius, have been repeatedly associated with CRC. In contrast, beneficial commensal microbes and their metabolites, especially short-chain fatty acids, may help maintain intestinal homeostasis and limit tumor-promoting processes. Because the gut microbiota is strongly shaped by diet, lifestyle, and environmental exposure, regional differences are also relevant. This is particularly important in Sichuan, China, where distinctive dietary habits and environmental features may influence microbial patterns associated with CRC risk and disease behavior. This review summarizes the main mechanisms linking the gut microbiota to CRC, examines the regional context of Sichuan, China, and discusses current and emerging clinical strategies. These include dietary intervention, probiotics, fecal microbiota transplantation, and microbiome-informed approaches to prevention, diagnosis, and treatment.

Colorectal cancer (CRC) is an increasing health concern in low- and middle-income countries (LMICs), especially in Africa, driven by dietary shifts, urbanisation, infections, and limited treatment access. The gut microbiome plays a central role in CRC, while soil-transmitted helminths (STHs) exert complex effects that can promote or mitigate risk depending on species, infection intensity, and host context. This systematic review synthesised 17 human studies (2000-2026) examining helminth impacts on gut microbial diversity, revealing a dualistic pattern. Several studies reported that chronic or moderate helminth infections, such as Ascaris lumbricoides and Trichuris trichiura, were associated with increased bacterial richness and the expansion of beneficial taxa, including Paraprevotellaceae, Parabacteroides, Agathobacter, Ruminococcaceae, and Lactobacillus. These taxa are associated with the production of short-chain fatty acids (SCFAs), protection of the epithelial barrier, and regulation of the immune system, suggesting a potential buffering effect against inflammation-driven carcinogenesis. On the contrary, other studies demonstrated helminth-associated dysbiosis characterised by reduced diversity and enrichment of pro-inflammatory and oncogenic taxa. T. trichiura and Strongyloides stercoralis infections were associated with the expansion of Treponema succinifaciens, Streptococcus gallolyticus, Enterobacteriaceae, and Ruminococcus torques, which are linked to reduced gut microbiome diversity, pro-inflammatory states, and oncogenic processes. Furthermore, A. lumbricoides infections altered the host microbiome at the phylum level, with increased Proteobacteria and reduced Firmicutes and Bacteroidetes, alongside metabolome shifts in amino acid and lipid pathways that have been associated with tumourigenic processes. Collectively, the evidence shows that helminthiasis may either enrich potentially protective microbes or be associated with pro-tumourigenic dysbiosis, with outcomes shaped by species, infection intensity, and host context. Notably, none of the included studies directly assessed CRC, underscoring the fact that current evidence is indirect and mechanistic. Overall, helminths are associated with gut microbiome shifts in both potentially protective and potentially harmful directions. This systematic synthesis of human evidence provides an integrated understanding of how helminth-associated microbiome shifts may influence colorectal carcinogenesis and highlights the need for longitudinal mechanistic studies to clarify causality and inform biomarker discovery and prevention in endemic regions.

Autism spectrum disorder (ASD) is a complex neurodevelopmental condition arising from interactions between genetic and environmental factors. The interplay between the microbiota-gut-brain axis and epigenetics has been implicated in ASD, but the extent of their impact remains unclear. We hypothesized that parental gut microbiota dysbiosis shapes cross-generationally shared DNA methylation patterns and ASD-like phenotypes in offspring. Antibiotic-treated adult mice were colonized with fecal microbiota from children with ASD or typically developing (TD) controls, then bred. Colonization with ASD-associated microbiota did not alter parental behavior but induced ASD-like behavioral changes in offspring, accompanied by colonic inflammation and neuronal loss in the hippocampus and striatum. Targeted bisulfite sequencing revealed that ASD-associated microbiota reshaped methylation at ASD-related CpG sites in parental brain, blood, and colon, with a subset of these alterations also observed in offspring tissue. Integrative analyses revealed sex-specific networks linking gut microbes, DNA methylation, gene expression, metabolites, and behavior. These findings support a model in which parental gut microbiota dysbiosis is associated with cross-generationally shared DNA methylation changes linked to ASD-like phenotypes in offspring. Together, these results provide novel microbial and epigenetic insights into ASD-related risk and offering a plausible mechanistic explanation for the clinical phenomenon in which unaffected parents give rise to children with ASD.

The purpose of this review is to provide a practical and clinically relevant overview of the role of the microbiome in the development and treatment of digestive tract cancers. We describe the established associations between microbes and malignancy, such as Helicobacter pylori and Fusobacterium nucleatum, in gastric and colorectal cancer, respectively. We also review emerging evidence identifying additional microorganisms that may play a role in digestive tract cancer initiation and progression. We discuss the impact of microbial composition on the efficacy and toxicity of cancer-directed therapies, including radiation therapy and systemic chemotherapy. Beyond outlining gut microbial risk factors, we also highlight interventions on the oral and gut microbiome to prevent or alleviate symptoms associated with dysbiosis, along with proposed strategies to improve therapeutic outcomes in the future. Finally, we examine opportunities to support gut microbial health, including suggestions to reduce exposure to environmental toxins that may increase cancer risk.

The oral microbiota, comprising bacteria, fungi, and viruses, plays a critical role in initiating food digestion, serving as the first defense against pathogenic invasion and maintaining oral homeostasis. In contrast, the gut microbiota, consisting of trillions of microorganisms, functions as a barrier protection, modulating the immune system and facilitating the absorption of nutrients. Although they have distinct anatomical locations, these ecosystems are highly interconnected and play a pivotal role in human health and disease. The most common routes of interaction between the oral and gut microbiota are the enteral, the hematogenous, and the immune cell migration routes. Many oral pathogens interact with intestinal microbes, activating the host's mechanisms that establish dysbiosis and pave the way for the development of various diseases, ranging from inflammatory bowel disease and colorectal cancer to metabolic and neurodegenerative disorders. In this review, we delineate the mechanisms underlying these ecosystems to offer novel insights into disease pathogenesis while also unveiling new avenues for preventive and therapeutic interventions. Although current therapeutic approaches include the administration of antibiotics, prebiotics, and probiotics, novel personalized therapeutic approaches have also emerged. Fecal microbiota transplantation (FMT), gut bacteria engineering, nanomedicine-based techniques, and the use of miRNA to foster microbiota balance in both compartments hold great promise and may prove critical for the prevention and management of systemic diseases.

Associations between the gut microbiome and cognitive decline remain inconsistent, reflecting methodological variability, small cohorts, and limited integration of behavioral and lifestyle factors. The microbiota-gut-brain axis may influence cognition through metabolic, immune, and neuroendocrine pathways affecting mood, decision-making, and health behaviors. This prospective, proof-of-concept study integrated multidimensional phenotyping with metagenomic sequencing (shotgun) in adults (50-90 y) around Washington, DC. Participants were classified as healthy controls (HC) or mild cognitive impairment (MCI) by clinical history; early Alzheimer's disease (eAD) participants were unable to complete study requirements. Longitudinal assessment used Boston Cognitive Assessment (BoCA), patient-reported outcomes (PROMIS-29), dietary intake and quality (DietID™), readiness-for-change (adapted URICA), at-home stool sample collection. Seventeen participants completed sufficient assessments (HC n = 11; MCI n = 6). Substantial overlap in gut microbiome composition was observed between HC and MCI. Poorly characterized or uncommon taxa drove trends; unassigned taxa were common. Assessment revealed high diet quality and variability in dietary patterns and key components (vegetables, whole grains, fat, fish). Participants demonstrated high readiness to engage in nutritional behavior change, with individuals with MCI reporting greater concern about maintaining changes and a stronger desire for external support. Integrating multidimensional phenotyping with metagenomics is feasible in cognitive decline. Findings highlight biological and behavioral heterogeneity, limitations of species-level inference, and diet and behavioral readiness as modifiable contextual factors.

The microbiota-gut-brain axis (MGBA) is a bidirectional network linking gut microbes to the CNS. This review elucidates how microbial messengers-short-chain fatty acids, bile acids, neuroactive metabolites, and extracellular vesicles-drive obesity and type 2 diabetes via neural, endocrine, and immune pathways. MGBA dysregulation triggers hypothalamic dysfunction, adipose inflammation, incretin axis impairment, and β‑cell failure. We discuss MGBA-targeted therapies and their translational challenges.

While metagenomics has transformed our view of microbial ecosystems, culture-based methods remain indispensable for accessing microbial functionality and biotechnological potential. In this study, we applied a culturomics strategy to explore the diversity, abundance, and distribution of culturable aerobic and facultative anaerobic bacteria along the gastrointestinal tract of dromedary camels (Camelus dromedarius) grazing on pristine desert flora. Using six culture media-including modified YCFA formulations-we isolated 97 bacterial species across 42 genera, 31 families, and four phyla: Firmicutes, Proteobacteria, Actinomycetota, and Bacteroidota. Strikingly, 88.6% of this diversity was recovered using YCFA-based media, and four candidate novel species were identified. The rumen harbored the most diverse and Gram-positive-dominated community, whereas the small intestine was enriched with Gram-negative taxa, many with pathogenic potential. These findings highlight the camel's unique physiological adaptation to extreme arid environments, characterized by efficient fiber degradation under nutrient- and water-limited conditions and the presence of stress-tolerant gut microbes capable of resisting acidic and osmotic challenges. Overall, this study establishes a foundational understanding of the camel gut microbiota and underscores the complementary power of culture-dependent methods to metagenomics. Future integration with anaerobic culturing and multi-omics analyses will further unveil the ecological and biotechnological potential of desert-adapted microbial life.

The gut microbiota and bile acids (BAs) exist in a tightly regulated, bidirectional relationship that influences host metabolism, immune function, and disease. Primary BAs synthesized in the liver are chemically transformed by intestinal microbes into a diverse pool of secondary BAs, which exert antimicrobial effects and activate host signaling pathways including Farnesoid X Receptor (FXR), Takeda G protein-coupled receptor 5 (TGR5), and sphingosine-1-phosphate receptor 2 (S1PR2). These pathways regulate BA homeostasis, epithelial barrier integrity, inflammation, and carcinogenesis. Disruption of this BA-microbiome axis has been implicated in biliary tract cancers (BTCs), a group of aggressive malignancies with rising global incidence and limited therapeutic options. Secondary BAs and BA receptor signaling contribute to tumor initiation and progression through NF-κB activation, oxidative stress, and altered cell survival, whereas reduced FXR signaling and obstructed enterohepatic circulation further promote inflammatory dysregulation. Emerging evidence demonstrates that microbial dysbiosis and altered BA metabolism are associated with distinct BTC microbial profiles, enriched in taxa such as Fusobacterium, Salmonella, Prevotella, and Actinomyces, alongside depletion of commensals including Lactobacillus. These taxa influence inflammatory signaling, BA transformation, and epithelial injury, contributing to carcinogenesis. Microbiome-BA interactions also shape anti-tumor immunity and responses to immune checkpoint inhibitors (ICIs). Specific microbial signatures-particularly enrichment of Lachnospiraceae, Erysipelotrichaceae, Bacteroidetes, and Alistipes-correlate with enhanced immune activation and improved clinical outcomes in hepatobiliary cancers. Modulation of gut microbiota through antibiotics, probiotics, or fecal microbiota transplantation can influence BA composition, immune surveillance, and therapeutic efficacy. Collectively, these data highlight the central role of the BA-microbiome axis in BTC pathogenesis and treatment response. Microbial and BA metabolite profiling represent promising avenues for biomarker development, while targeted manipulation of BA signaling and microbial ecology offers potential therapeutic strategies to improve BTC outcomes.

The gut-liver axis is a two-way communication network where gut microbes and their metabolites affect liver function, while the liver regulates the intestinal environment through bile acids, immune factors, and antimicrobial substances. Disruption of this balance contributes to various liver diseases, including nonalcoholic fatty liver disease, alcohol-associated liver disease, cirrhosis, and liver cancer. Probiotics and synbiotics are potential therapies that aim to restore microbial balance, strengthen the intestinal barrier, and regulate inflammation and metabolism. Recent omics technologies, such as metagenomics, metabolomics, transcriptomics, and proteomics, have helped uncover how these interventions influence important pathways involving short-chain fatty acids, bile acids, and microbial metabolites. Studies suggest that probiotics and synbiotics may improve liver health through effects on metabolism, immune regulation, and fibrosis, although results vary depending on the specific microbial strains and patient characteristics. Emerging approaches include next-generation probiotics, targeted synbiotic combinations, and personalized microbiome-based treatments. Combining multi-omics data with digital health tools may help identify patients who are most likely to benefit. Overall, microbiota-targeted therapies show promise as personalized strategies for managing liver diseases, but further research is needed to overcome challenges in translating findings into consistent clinical applications.

The crucial role of the gut microbiome in human health has driven a need to understand bacterial function within their complex native ecosystem. However, traditional functional genomic methods require isolating, cultivating, and modifying bacteria in vitro before their reintroduction in vivo. This process often necessitates the use of axenic animals or antibiotic treatments, creating artificial conditions that disrupt key microbial interactions and can obscure relevant phenotypes. This review highlights emerging tools for precise, in situ genetic manipulation of bacteria directly within the gut. We cover diverse technologies, including DNA delivery systems (e.g. engineered temperate phages, phagemids, and conjugative plasmids), and genetic perturbation strategies (e.g. CRISPR-Cas tools and transposons). These methods offer the opportunity to engineer unculturable microbes in their natural habitat and conduct genetic screens to investigate the role of specific genes and pathways. Finally, we explore the potential therapeutic applications of in situ microbiome editing.