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Mechanistic Insights Into the Association Between Gut Microbiota Diversity and Atherosclerosis, Acute Coronary Syndrome, and Peripheral Arterial Disease Progression.

BACKGROUND: The gut microbiome has emerged as a potential contributor to cardiovascular diseases (CVDs), including atherosclerosis, acute coronary syndrome (ACS), and peripheral arterial disease (PAD). While observational studies link dysbiosis to CVD, causal relationships remain uncertain. METHODS: This narrative review synthesizes evidence from human observational studies, clinical interventions, and experimental models to distinguish association from mechanistic plausibility and clinical causality. Literature was searched through July 2026 in PubMed/MEDLINE, Web of Science, and Scopus. RESULTS: Microbial metabolites-including trimethylamine N-oxide (TMAO), short-chain fatty acids (SCFAs), bile acids, and lipopolysaccharide (LPS)-modulate endothelial function, immune cell programming, platelet activity, and plaque stability through receptor-mediated signaling and epigenetic regulation. SCFAs demonstrate potentially protective effects via GPCR and HDAC pathways, while TMAO is associated with atherothrombotic risk. However, much mechanistic evidence derives from preclinical studies. Heterogeneity from diet, geography, host characteristics, renal function, and medications substantially influences microbiota-CVD associations. CONCLUSION: The gut-vascular connection is biologically plausible, but definitive clinical causality remains unproven. Microbiome-directed therapies (dietary modulation, pre/pro/synbiotics, targeted metabolite inhibition) are investigational. Prospective, standardized, adequately powered human studies with clinically meaningful outcomes are essential before routine cardiovascular application.

Gastrointestinal Microbiome↗

Recurrent and niche-specific functional bacteriome of maize hybrid revealed by integrated metabarcoding and culturomics.

The plant microbiome plays a pivotal role in plant survival in natural habitats by facilitating nutrient acquisition, stress adaptation, and disease suppression, while also offering opportunities to enhance crop productivity and climate resilience. However, the distribution of persistent and culturable bacteriome across maize-associated niches and their functional potential remain poorly resolved. This study integrated metagenomic next-generation sequencing (mNGS-based metabarcoding) and culturomics to characterise the maize-associated bacteriome of bulk soil, rhizoplane, phylloplane, and cob of the maize hybrid PHM-1 under contrasting cropping and tillage systems, and to identify recurrent and agriculturally promising bacteriome components. The bacteriome exhibited pronounced niche-specific structuring, whereas overall bacterial community composition did not differ significantly across cropping and tillage treatments (ANOSIM, R = 0.038, p = 0.306). Proteobacteria predominated in the culturable bacteriome (69-84%; mean, 76.2%) but accounted for only 1% of the total bacteriome, whereas Patescibacteria and Firmicutes were relatively enriched. Niche-specific dominance was evident, with Pantoea accounting for 40.79% of the total and 56.27% of the culturable phylloplane bacteriome under cereal monocropping, while Serratia represented 31.59% and 59.40% of the total and culturable cob bacteriomes, respectively. Across niches, mNGS captured substantially greater bacteriome diversity, particularly uncultured and unidentified taxa in soil-associated compartments, whereas culturomics recovered a narrower but functionally accessible fraction. Culturomics yielded 99 isolates representing 32 species across 12 genera, including six genera shared with the mNGS-derived recurrent bacteriome: Bacillus, Enterobacter, Pantoea, Pseudomonas, Serratia, and Stenotrophomonas. Functional screening identified strong biocontrol and plant-beneficial traits among core-associated isolates. Pseudomonas oryzihabitans ZM-DL-PA10 inhibited Rhizoctonia solani, Macrophomina phaseolina, and Bipolaris maydis by up to 40.6%, 43.9%, and 45.2%, respectively, through secreted and volatile metabolites; exhibited P, K, and Zn solubilisation; and produced IAA and siderophores. It also recorded the lowest B. maydis disease index (ADI) of 1.00. Pantoea ananatis ZM-BH-EA4 showed 52.4% and 68.5% inhibition of R. solani and B. maydis, respectively, through volatile metabolites. Collectively, the integration of mNGS and culturomics revealed a strongly compartmentalised maize bacteriome and identified recurrent, culturable, and functionally promising bacterial taxa, providing a targeted resource for microbiome-based crop protection and climate-resilient maize production.

Zea mays↗

Species-specific structuring of gut bacterial and fungal communities in honey bees Apis cerana and Apis mellifera.

Honey bee gut microbiome studies have primarily emphasized bacteria, leaving fungal communities comparatively overlooked despite their ecological and functional importance. Whole-genome shotgun metagenomics of Apis cerana and Apis mellifera revealed fungal assemblages dominated by Ascomycota, with Basidiomycota and Microsporidia in minor proportions, alongside gut bacterial communities composed mainly of Pseudomonadota, Bacillota, and Actinomycetota. The bacterial diversity was markedly higher in A. mellifera (Shannon = 5.90; Simpson = 0.98) than in A. cerana (Shannon = 4.01; Simpson = 0.94; p > 0.05), while fungal diversity remained comparable between species (p > 0.05). Beta-diversity analyses revealed strong host-specific clustering for both bacterial (PERMANOVA R2 = 0.7989, p > 0.05) and fungal communities (R2 = 0.7218, p > 0.05), indicating distinct microbial organization driven by host species. Bacterial-fungal co-occurrence patterns exhibited host-specific structuring, suggesting differential inter-kingdom community organization between A. cerana and A. mellifera. Linear Discriminant Analysis Effect Size (LEfSe) identified 93 discriminatory fungal taxa (45 enriched in A. cerana, 48 in A. mellifera), highlighting yeast-dominated signatures in A. mellifera and Basidiomycota-affiliated enrichments in A. cerana. KEGG and CAZy profiling revealed host- and kingdom-specific functional differences, with bacterial communities of A. mellifera showing distinct representation of carbohydrate metabolism and nutrient-cycling functions, while fungal communities exhibited a comparatively narrower functional repertoire. Together, these findings provide a high-resolution view of honey bee bacterial and fungal microbiomes, highlighting strong host-driven divergence in taxonomy, function, and cross-kingdom interactions.

Animals↗

Comprehensive analyses of a large human gut Bacteroidales culture collection reveal species- and strain-level diversity and evolution.

Species of the Bacteroidales order are among the most abundant and stable bacterial members of the human gut microbiome, with diverse impacts on human health. We cultured and sequenced the genomes of 408 Bacteroidales isolates from healthy human donors representing nine genera and 35 species and performed comparative genomic, gene-specific, metabolomic, and horizontal gene transfer analyses. Families, genera, and species could be grouped based on many distinctive features. We also observed extensive DNA transfer between diverse families, allowing for shared traits and strain evolution. Inter- and intra-species diversity is also apparent in the metabolomic profiling studies. This highly characterized and diverse Bacteroidales culture collection with strain-resolved genomic and metabolomic analyses represents a valuable resource to facilitate informed selection of strains for microbiome reconstitution.

Humans↗

Mechanisms linking the gut microbiota to colorectal cancer development and progression.

Colorectal cancer remains a leading cause of global cancer mortality, with a concerning rise in early-onset cases driven by complex interactions between environmental exposures, lifestyle factors, and host genetics. Mounting evidence indicates that gut microbiota dysbiosis critically modulates this oncogenic process, acting as an active participant rather than a passive bystander. This review systematically synthesizes the dichotomous roles of the intestinal microbiome in colorectal tumorigenesis through the conceptual framework of the driver-passenger model. We discuss how early initiating driver bacteria, such as Polyketide synthase-positive Escherichia coli and enterotoxigenic Bacteroides fragilis, compromise mucosal barriers, induce chronic mucosal inflammation, and inflict direct genomic instability. As the local tumor microenvironment undergoes profound metabolic remodeling, opportunistic passenger pathogens, notably Fusobacterium nucleatum, become enriched, further promoting cellular proliferation and facilitating tumor immune evasion. Conversely, protective commensals, exemplified by Clostridium butyricum and Streptococcus thermophilus, exert robust tumor-suppressive effects through multifaceted mechanisms. These beneficial microbes actively antagonize malignant progression by redirecting tumor metabolic fluxes toward oxidative stress, orchestrating deep epigenetic reprogramming, and degrading core oncoproteins to reverse chemoresistance. Transitioning from fundamental mechanisms to clinical application, we evaluate a comprehensive spectrum of microbiota-targeted interventions, encompassing non-invasive diagnostic biomarkers, fecal microbiota transplantation, engineered bacteria, phage therapy, and postbiotics. Finally, we critically address the formidable translational challenges associated with microbial heterogeneity, long-term safety, and regulatory standardization, aiming to provide a balanced perspective on integrating microbiome-based strategies into next-generation precision oncology for colorectal cancer.

Humans↗

Interkingdom remodeling of the intestinal bacteriome and virome during Toxoplasma gondii infection in rats.

Toxoplasma gondii infection is associated with intestinal microbiome disruption, but its effects on genome-resolved bacterial populations, the gut virome, and bacteriome-virome relationships remain poorly understood. Using previously generated shotgun metagenomic datasets from 36 intestinal samples collected from 18 Sprague-Dawley rats across control, acute, and chronic infection groups, we reconstructed 294 quality-filtered, non-redundant bacterial metagenome-assembled genomes (MAGs) and identified 899 medium-to-high-quality viral operational taxonomic units (vOTUs) from assembled metagenomic contigs. Infection was associated with reduced bacterial richness in the small intestine during both acute and chronic stages and lower Shannon diversity during chronic infection. In contrast, large-intestinal α-diversity remained stable despite significant compositional reorganization. Taxonomic changes included increased Lactobacillus intestinalis, Limosilactobacillus reuteri, and Prevotella sp900547005, together with decreased Rothia sp002492045 and Akkermansia muciniphila. Functional profiling revealed region- and stage-specific changes in predicted bacterial metabolic potential, including reduced energy-related pathways and carbohydrate-active enzyme abundance. The virome also showed significant compositional changes in both intestinal regions. Quimbyviridae and Podoviridae_crAss-like viruses decreased in the small intestine during chronic infection, while Quimbyviridae, Flandersviridae, and Podoviridae_crAss-like viruses showed stage-specific decreases in the large intestine. Predicted bacterial hosts were assigned to 48.39% of vOTUs, with Lachnospiraceae and Ruminococcaceae being the most frequently linked families. Trans-kingdom networks further revealed region-specific positive and negative abundance correlations between bacterial and viral taxa. These findings extend previous microbiota-metabolome observations by integrating genome-resolved bacteriome analysis with contig-based virome profiling, providing a foundation for future mechanistic studies of toxoplasmosis-associated microbiome remodeling.

Gut virome↗

Fecal microbiota transplantation promotes type 2 mucosal immune responses with colonic epithelium proliferation in patients with recurrent Clostridioides difficile.

BACKGROUNDFecal microbiota transplantation (FMT) is the most effective therapy for recurrent Clostridioides difficile infection (rCDI), yet its mechanism of action remains poorly understood.METHODSWe report the results of a clinical trial of patients undergoing FMT therapy for rCDI (n = 16), which analyzed colon biopsies, plasma, PBMCs, and stool at the time of FMT and 2-month follow-up. Plasma and colon biopsy samples were also collected from healthy controls for comparison with patients with rCDI. Microbiome composition, colonic gene expression, and immune changes were evaluated through high-throughput sequencing and immunoprofiling via flow cytometry.RESULTSNo patients experienced recurrence at follow-up. FMT significantly altered the intestinal microbiome but had no significant impact on the systemic immune system. In contrast, FMT promoted broad changes in colonic transcriptional profiles compared with both pre-FMT and healthy control biopsies, inhibiting genes associated with proinflammatory signaling and upregulating type 2 immunity and proliferative pathways (Myc and mTORC1). FMT increased expression of IL-33 and the type 2 immune EGFR family ligand amphiregulin, potentially explaining upregulation of Myc and mTORC1 pathways. Spatial transcriptomics demonstrated that these changes were localized to the colonic epithelium. Comparison of transcriptional profiles with available single-cell gene sets determined that post-FMT biopsies were enriched in signatures associated with proliferative cell types while repressing signatures of differentiated colonocytes.CONCLUSIONWe conclude that FMT promotes proliferation of the colonic epithelium in patients with rCDI, which may drive regeneration and protect against subsequent CDI.TRIAL REGISTRATIONClinicaltrials.gov NCT02797288.FUNDINGThis work was funded by grants from the NIH.

Adult↗

Characterization of gut microbiota and metabolites in renal transplant recipients during COVID-19 and prediction of one-year allograft function.

BACKGROUND: The gut-lung-kidney axis is pivotal in immune-related kidney diseases, with gut dysbiosis potentially exacerbating the severity of Coronavirus disease 2019 (COVID-19) in recipients of kidney transplant. This study aimed to characterize the gut microbiome and metabolome in renal transplant recipients with COVID-19 pneumonia over a one-year follow-up period. METHODS: A total of 30 renal transplant recipients were enrolled, comprising 17 with COVID-19 pneumonia, six with mild COVID-19, and seven without COVID-19. Fecal samples were collected at the onset of infection for gut microbiome and metabolome analysis. Generalized Estimating Equations (GEE) model and Latent Class Growth Mixed Model (LCGMM) were employed to dissect the relationships among clinical characteristics, laboratory tests, and gut microbiota and metabolites. RESULTS: Four microbial phyla (Deferribacteres, TM7, Fusobacteria, and Gemmatimonadetes) and 13 genera were significantly enriched across three recipients groups, correlating with baseline inflammatory response and allograft function. Additionally, 52 differentially expressed metabolites were identified, with seven significantly correlating with eight altered microbiota genera. LCGMM revealed two distinct classes of recipients, with those suffering from COVID-19 pneumonia exhibiting significantly elevated serum creatinine (Scr) trajectories over the one-year period. GEE further identified 12 genera and 181 metabolites closely associated with these trajectories; a multivariable model incorporating gut metabolites of 1-Caffeoylquinic Acid and PMK was found to effectively predict one-year allograft function. CONCLUSIONS: Our study indicates a possible interaction between the composition of the gut microbiota and metabolites community and COVID-19 in renal transplant recipients, particularly in relation to disease severity and the prediction of one-year allograft function.

Humans↗

Deciphering microbial and metabolic influences in gastrointestinal diseases-unveiling their roles in gastric cancer, colorectal cancer, and inflammatory bowel disease.

INTRODUCTION: Gastrointestinal disorders (GIDs) affect nearly 40% of the global population, with gut microbiome-metabolome interactions playing a crucial role in gastric cancer (GC), colorectal cancer (CRC), and inflammatory bowel disease (IBD). This study aims to investigate how microbial and metabolic alterations contribute to disease development and assess whether biomarkers identified in one disease could potentially be used to predict another, highlighting cross-disease applicability. METHODS: Microbiome and metabolome datasets from Erawijantari et al. (GC: n = 42, Healthy: n = 54), Franzosa et al. (IBD: n = 164, Healthy: n = 56), and Yachida et al. (CRC: n = 150, Healthy: n = 127) were subjected to three machine learning algorithms, eXtreme gradient boosting (XGBoost), Random Forest, and Least Absolute Shrinkage and Selection Operator (LASSO). Feature selection identified microbial and metabolite biomarkers unique to each disease and shared across conditions. A microbial community (MICOM) model simulated gut microbial growth and metabolite fluxes, revealing metabolic differences between healthy and diseased states. Finally, network analysis uncovered metabolite clusters associated with disease traits. RESULTS: Combined machine learning models demonstrated strong predictive performance, with Random Forest achieving the highest Area Under the Curve(AUC) scores for GC(0.94[0.83-1.00]), CRC (0.75[0.62-0.86]), and IBD (0.93[0.86-0.98]). These models were then employed for cross-disease analysis, revealing that models trained on GC data successfully predicted IBD biomarkers, while CRC models predicted GC biomarkers with optimal performance scores. CONCLUSION: These findings emphasize the potential of microbial and metabolic profiling in cross-disease characterization particularly for GIDs, advancing biomarker discovery for improved diagnostics and targeted therapies.

Humans↗

Gut microbial and functional alterations lead to metagenomic signatures for midgut neuroendocrine tumor patients and for carcinoid syndrome.

Midgut neuroendocrine tumors (NET) derive from enterochromaffin cells, which have a close interrelationship with intestinal microbiota. Recently, we have utilized 16S rRNA sequencing to uncover that midgut NET patients have a depleted gut microbiome and a specific fecal microbial signature. This study aims to validate these findings and to further characterize the role of microbes and microbial metabolic pathways in midgut NET patients with and without carcinoid syndrome (CS). Fecal samples from 60 midgut NET patients and 20 household-matched controls were subjected to whole metagenome sequencing. The gut microbial community composition of midgut NET patients differed from that of controls, with 2 genera, 17 species and 9 microbial pathways showing differential abundance (P < 0.001). No differences in the microbial composition were observed between midgut NET patients with and without CS (P > 0.05). However, we did observe changes in inter-genus correlations of Bacteroides, Odoribacter, Parasutterella, Klebsiella, Ruminococcus and Proteobacteria when comparing these two patient groups. A signature of 16 microbial species (area under the receiver operating characteristics (AUROC) curve 0.892) or 18 microbial pathways (AUROC 0.909) accurately predicted the presence of a midgut NET. Furthermore, a microbial signature consisting of 14 functional microbial pathways distinguished CS patients from non-CS patients (AUROC 0.807). Thus, this study confirms that the gut microbiome of midgut NET patients is altered at the metagenomic level, which is not related to the presence of CS. A fecal microbial signature could constitute a novel biomarker for the diagnosis of midgut NET or CS.

Aged↗

Effects of Different Feeding Patterns on the Gut Virome of 6-Month-Old Infants.

The gut microbiome is essential for infant health, and in recent years, the impact of enteroviruses on infant health and disease has received increasing attention. The transmission of breast milk phages to the infant gastrointestinal tract contributes to the shaping of the infant gut virome, while breastfeeding regulates the colonization of the infant gut virome. In this study, we collected fecal samples from healthy infants and analyzed the distribution characteristics of infant viral communities by viral metagenomic analysis, and analyzed the differences in infant viral communities under different feeding practices. Our results indicate that the infant intestinal virome consists of phages and eukaryotic viruses. Caudovirales and Microviridae dominated the phage composition, and except for Siphoviridae, which was more predominant in the intestines of formula-fed infants, there were no significant differences in the overall abundance of other Caudovirales and Microviridae in the intestines of infants with different feeding patterns. Breastfeeding can lead to a higher diversity of infant gut viruses through vertical transmission, and a highly diverse gut virome helps maintain the maturation of the gut microbiome. This study informs the shaping of gut virome in healthy infants by breastfeeding and contributes to further research on infant gut virome characteristics and formation processes.

Humans↗

Microbial partnerships and molecular mechanisms in plant stress physiology for climate-resilient and sustainable farming.

Plant-microbial partnerships and their underlying molecular mechanisms are indispensable, natural drivers of improved nutrient acquisition and stress tolerance in the face of climate-driven environmental challenges. Modern multi-omics tools, when coupled with artificial intelligence and synthetic biology, enable the precise design of targeted bioinoculants and synthetic microbial consortia. Translating these advanced microbiome-based strategies into scalable, field-level agricultural applications provides a sustainable path toward securing global food production while maintaining soil health. Global climate change imposes multifaceted abiotic and biotic stresses on crops, disrupting physiological and molecular processes and threatening agricultural productivity. Plant-associated microbes represent an underexplored yet powerful ally in enhancing crop resilience. This review presents current knowledge of plant-microbe interactions and the molecular mechanisms governing plant stress physiology, with an emphasis on climate-resilient and sustainable farming. Hence, ever-changing environmental cues pose a significant burden on agricultural productivity, and plant-associated microbial communities modulate a cascade of physiological and molecular responses, including production of phytohormones, signaling, regulation of reactive oxygen species homeostasis, and activation of plant immune responses to help plants withstand stress and enhance productivity. Moreover, root exudates, phytohormones, and quorum sensing mediate the central communication networks, facilitating plant-microbe cross talk. Additionally, the advances in OMICs approaches aid in disentangling the molecular underpinnings of these interactions by providing mechanistic insights and potential candidate gene targets for crop improvement and stress resilience. In the post-genomic era, integrating artificial intelligence and big data analysis to optimize microbiome-based strategies for sustainable agriculture is a new frontier for disentangling plant-microbe symbiosis to improve soil health, enhance crop yields, and improve stress tolerance. Thus, by integrating the ecological, physiological, and molecular perspectives, this review highlights the transformative potential of harnessing plant-microbe symbiosis for climate-resilient and sustainable agriculture.

Stress, Physiological↗

Early-Onset Colorectal Cancer: Clinical and Molecular Features with Emerging Insights from Comprehensive Genomic Profiling.

Early&#x2011;onset colorectal cancer (EOCRC), defined as colorectal cancer (CRC) diagnosed before 50 years of age, is increasing globally. Colorectal cancer is currently the third most commonly diagnosed cancer and the second leading cause of cancer-related death worldwide, with GLOBOCAN 2024 estimating approximately 2.04 million new cases and 917,895 deaths in 2024. Recent studies indicate a sustained rise in EOCRC incidence across multiple regions and birth cohorts, with the greatest increases observed among younger adults. Although hereditary cancer syndromes account for 20-25% of EOCRC cases, most occur in the absence of known genetic predispositions or established risk factors. Emerging evidence implicates the gut microbiome as a potential contributor to EOCRC, with distinct microbial signatures differentiating it from late&#x2011;onset colorectal cancer (LOCRC) diagnosed after 50 years of age. This review synthesizes current evidence on clinical, molecular, and diagnostic features distinguishing EOCRC from LOCRC, including differences in anatomical distribution, histopathology, genomic and epigenetic alterations, microbiome composition, and immune landscape, and discusses their implications for personalised screening and therapeutic strategies. We performed a retrospective secondary analysis of comprehensive genomic and immune profiling data from 1737 patients with colorectal cancer tested between June 2021 and June 2023. The analysis showed that tumours arising in patients with EOCRC had lower tumour mutational burden than tumours diagnosed as LOCRC, whereas other immune-related biomarkers, including tumour immunogenicity score, did not remain significantly different after correction for multiple testing. Despite these emerging biological differences, current screening strategies remain largely dependent on an age threshold of 50 years, and EOCRC is not addressed by age&#x2011;specific treatment approaches. We therefore review the translational potential of emerging biomarkers, including microbial signatures and liquid biopsy approaches, and propose a framework for integrating molecular profiling into clinical practice. Finally, we highlight the unmet need for coordinated efforts to improve screening in younger populations, address fertility preservation considerations, and ensure adequate psychosocial support for patients with EOCRC.

Early-onset colorectal cancer↗

Metabolic reprogramming and taxonomic drivers in bacterial vaginosis: A large-scale metagenomic meta-analysis.

OBJECTIVE: Bacterial vaginosis (BV) represents a profound ecological shift from a Lactobacillus-dominated microbiota to a diverse polymicrobial biofilm associated with adverse outcomes. While taxonomic signatures are well-documented, the functional mechanisms driving this transition remain obscured. This study elucidates the genomic potential for metabolic reprogramming and the putative "functional handover" underpinning the stability of the dysbiotic state. METHODS: A computational meta-analysis of 3557 vaginal microbiomes from diverse global cohorts was performed using the standardized MGnify pipeline. A high-resolution subset of 187 whole-genome shotgun (WGS) metagenomes was stratified to compare functional potential across demographic groups. Taxon-function interaction networks were constructed, utilizing a dual-filter statistical approach (p&#x202f;<&#x202f;0.05 and effect size ranking), to map the shift from homeostatic maintenance to dysbiotic metabolic potential. RESULTS: BV was characterized by a fundamental shift from "maintenance" pathways to high-turnover "growth-oriented" genomic repertoires. While ABC transporter-like domains were present in healthy communities, dysbiosis was marked by a quantitative expansion and diversification of these systems alongside P-loop NTPases. Network analysis revealed a putative "functional handover": while Gardnerella serves as the adherent structural scaffold, the metabolic burden appears to be associated with secondary anaerobes, specifically BVAB1 and Sneathia, which exhibit strong genomic correlations with nutrient transport and stress response pathways. Crucially, microbiomes from women of African ancestry (Black cohort) exhibited a distinct functional profile with genomic signatures consistent with functions previously associated with resistome expansion (e.g., tetracycline/macrolide resistance), contrasting with Asian cohorts. CONCLUSION: BV is a state of metabolic reprogramming where genomic functional dominance is transferred from Lactobacillus to a cooperative network of anaerobic opportunists. Identifying BVAB1 and Sneathia as candidate metabolic engines, supported by a Gardnerella scaffold, challenges current therapeutic paradigms and highlights the potential for precision medicine targeting specific functional drivers and resistome profiles across diverse populations.

Humans↗

Metax enables accurate cross-domain taxonomic profiling of metagenomes.

Taxonomic profiling is fundamental to microbiome research, yet achieving high species-level accuracy remains challenging for complex communities that span bacteria, viruses, eukaryotes, and archaea, and these limitations are exacerbated in low-biomass, host-dominated samples. We introduce Metax, a cross-domain taxonomic profiler that integrates coverage-based probabilistic modeling with an expectation-maximization framework to distinguish true microbial signals from artifacts. Across >600 samples from host-associated, environmental, wastewater, and low-biomass clinical settings, including benchmarks with limited reference representation, Metax improved profiling accuracy, achieving on average 55% higher F1 scores and 45% lower Bray-Curtis dissimilarity than other methods. Moreover, this broad evaluation demonstrated that Metax resolved bacterial and viral signatures of peri-implantitis in oral microbiomes and revealed signals suggestive of reagent-borne contaminants and reference misassemblies in plasma-cell-free DNA. By leveraging genome-wide coverage evidence, Metax enables robust cross-domain profiling across diverse sample types and sequencing depths, including settings where reference databases are highly incomplete.

abundance estimation↗

Lactobacillus iners at the nexus of microbiota, immunity, and pregnancy.

Pregnancy induces a dynamic reconfiguration of the vaginal microbiome, typically marked by increased dominance of Lactobacillus species and reduced microbial diversity. Among these bacteria, Lactobacillus iners stands out for its unique genomic traits, controversial associations with vaginal health, and frequent presence across all stages of gestation. This review synthesizes current literature on the maternal microbiome with a focus on L. iners, exploring its strain-level diversity, metabolic idiosyncrasies, and inflammatory potential. We discuss how host factors such as ethnicity, sexual activity, maternal age, and especially obesity, influence microbial composition, and evaluate conflicting data surrounding L. iners in contexts like in vitro fertilization, preterm birth, and postpartum recovery. Emerging evidence suggests that L. iners may act as a transitional species, whose effect on pregnancy outcomes depends on its abundance, genetic features, and interactions with the host immune system. We also assess limitations of current animal models and propose future directions for understanding this enigmatic bacterium. Unraveling the role of L. iners will be essential to predicting, preventing, and managing adverse pregnancy outcomes in diverse populations.

Humans↗

The role of mobile genetic elements in adaptation of the microbiota to the dynamic human gut ecosystem.

The human intestinal microbiota is a dynamic ecosystem shaped by extensive horizontal gene transfer, particularly in individuals from industrialized populations. In this review, we discuss recent advances in our understanding of how mobile genetic elements (MGEs) contribute to microbial ecology and evolution in this diverse community, focusing on MGEs carrying fitness-conferring genes. Bacteroidales species can colonize individuals for decades and serve as major hubs for MGE exchange. Most MGEs are highly variable across individuals and geographies. Occasionally, conserved MGEs can spread across geography and lifestyles. Functional characterizations of MGEs reveal their roles in antibiotic resistance, interbacterial antagonism, biofilm formation, immune evasion, and nutrient acquisition, among others. Substantive progress in our understanding of MGEs in the gut microbiome offers promising avenues for therapeutic microbiome interventions. However, major challenges remain in functional prediction, host-MGE linkage, and experimental characterization.

Humans↗

Gut microbial genomes with paired isolates from China illustrate probiotic and cardiometabolic effects.

The gut microbiome displays genetic differences among populations, and characterization of the genomic landscape of the gut microbiome in China remains limited. Here, we present the Chinese Gut Microbial Reference (CGMR) set, comprising 101,060 high-quality metagenomic assembled genomes (MAGs) of 3,707 nonredundant species from 3,234 fecal samples across primarily rural Chinese locations, 1,376 live isolates mainly from lactic acid bacteria, and 987 novel species relative to worldwide databases. We observed region-specific coexisting MAGs and MAGs with probiotic and cardiometabolic functionalities. Preliminary mouse experiments suggest a probiotic effect of two Faecalibacillus intestinalis isolates in alleviating constipation, cardiometabolic influences of three Bacteroides fragilis_A isolates in obesity, and isolates from the genera Parabacteroides and Lactobacillus in host lipid metabolism. Our study expands the current microbial genomes with paired isolates and demonstrates potential host effects, contributing to the mechanistic understanding of host-microbe interactions.

Probiotics↗