Maternal-fetal infections are a leading cause of morbidity and mortality, often requiring complex antibiotic treatments due to increasing antibiotic resistance. However, the determinants of resistance in the vaginal microbiome (VMB) remain underexplored. We characterized a cohort of 1547 pregnant women and show that the VMB harbors a wide range of antibiotic resistance genes (ARGs). Genes conferring resistance to Macrolide-Lincosamide-Streptogramin (MLS) and tetracycline antibiotic classes were the most abundant, whereas those from ß-lactam class were the most diverse. ARG diversity was found to be primarily shaped by microbial community state types (CSTs), with CST I (Lactobacillus crispatus-dominated community) showing the lowest and CST IV (anaerobic species-dominated community) the highest diversity. Co-abundance patterns further revealed modular structures linking specific taxa (e.g., Gardnerella, Prevotella, and Enterobacterales) to distinct ARGs and mobile genetic element profiles. A novel method incorporating predicted ARGs phenotypes, which we call the Phenotypic Resistance Diversity Index (PRDI), uncovered a resistome signature linked to adverse pregnancy outcomes, including increased microbial diversity and expanded predicted antibiotic resistance breadth in preterm premature rupture of membranes. Overall, our study establishes the VMB as a structured and dynamic reservoir of ARGs, contributing to the broader human resistome, opening new perspectives for advancing maternal and neonatal care.
Maintaining biological stability is essential for high microbiological water quality in drinking water distribution systems (DWDS). Although treatment without residual disinfectant removes biodegradable organic matter to limit microbial regrowth, it remains unclear how improved biological stability influences microbial communities during distribution. We investigated habitat-specific microbial communities in two full-scale DWDS supplied with the same surface water source but treated differently. Conventionally treated drinking water was compared with water produced by managed aquifer recharge and recovery, and the additional effect of ultrafiltration (UF) post-treatment was evaluated. Microbial communities in habitats (bulk drinking water, biofilms and loose deposits) were characterized using 16S rRNA gene amplicon sequencing and analysed together with biological stability, physicochemical and cultivation-based measurements. Improved biological stability reduced regrowth potential and Aeromonas occurrence while altering microbial communities. Treatment established the initial microbial community, but UF-post treatment and storage reshaped this community, increasing cell numbers and promoting the dominance of Comamonadaceae and Brevundimonas. During distribution, loose deposits increasingly contributed to bulk drinking water communities, although this effect was reduced after UF. Loose deposits showed stronger seasonal variation than bulk drinking water. These findings show that biological stability shapes microbial communities and identifies loose deposits as an important habitat for understanding and monitoring regrowth.
Ageing is associated with changes in the human gut bacterial microbiome: with age, it becomes more diverse, intra- and interindividual variability increases and it shows a decline in core bacterial genera and an expansion of rarer genera. While recent evidence in model organisms suggests these patterns may arise through stochastic processes rather than host-driven selection, the role of life-time exposures, or the exposome, remains poorly understood. Here, we characterise age-related gut microbiome dynamics in 165 bonobos (Pan paniscus) from wild and zoo-housed populations, aged 2 to 71 years, providing a comparative framework to disentangle conserved from context-dependent ageing trajectories in the gut microbiome in hominids. Across both environments, ageing was associated with increased microbial diversity and reduced core microbiome abundance, paralleled by a rise in low-abundance taxa, recapitulating patterns seen in humans. Notably, instability and uniqueness increased with age in zoo-housed, but not wild bonobos, mirroring patterns restricted to industrialised human populations. Moreover, cumulative exposure to distinct environments over an individual’s lifetime substantially contributes to microbiome uniqueness. Our findings suggest that while gut microbiome ageing is broadly conserved across hominids, its expression is modulated by environmental context, offering insight into the evolutionary and ecological drivers of microbial ageing in humans.
Gut microbial communities modulate host physiology through diverse bioactive functional outputs; however, how microbiome-derived signals shape neuroinflammatory states remains incompletely understood. Here, we identified Streptococcus parasanguinis (S. parasanguinis, G14) as a gut-enriched commensal associated with elevated neuroinflammatory activity in the context of temporal lobe epilepsy (TLE). In a lithium‒pilocarpine-induced mouse model, S. parasanguinis colonization exacerbated inflammatory signalling, accompanied by increased expression of Tnf-α, Il-1β, Il-6 and Ccl2. Mechanistic analyses revealed that these effects were mediated by bacterial extracellular vesicles (BEVs). S. parasanguinis-derived BEVs (S. p BEVs) promoted peripheral and central inflammatory responses, potentially through peripheral immune-to-brain signalling. Notably, BEVs induced the expression of several ARM-associated genes in microglia, suggesting an ARM-associated activation pattern. Together, these findings position BEVs as potential mediators of gut microbiome–host communication, linking microbial ecology to neuroinflammatory activation through a BEV–CCL2–microglial inflammatory axis.
Bacteriophage-derived depolymerases provide promising scaffolds for the rational design of next-generation anti-biofilm peptides. We report two novel lytic Caudoviricetes phages φAB440 and φAB441, targeting multidrug-resistant hypermucoviscous Acinetobacter baumannii, encoding tail-associated depolymerases with pectate lyase domains and endolysins featuring glycoside hydrolase motifs. Depolymerases and endolysins demonstrated high binding affinity towards capsular polysaccharide K15 (−9.2 kcal/mol) and NAG-NAM tetramers (−7.86 kcal/mol). Synteny analysis revealed significant genome rearrangement and divergence in both phages, more strongly in φAB441. Phage φAB441’s rare codon bias enables efficient depolymerase expression with altered tRNA availability in biofilms. Phages φAB440 and φAB441 suppressed bacterial growth over 24 h at low MOIs (10⁻¹ and 10⁻³), without evidence of resistance development. Four-day-old biofilms formed on urinary catheters were completely eradicated at 10⁹-108 PFU/ml, with ~7.2–7.4 log₁₀ CFU reductions. Phage φAB441, when tested against A. baumannii infection in Caenorhabditis elegans, increased survival of nematodes to 75.97%, 73.97%, and 73.7% at MOIs 1000, 100, and 10, respectively. Our findings highlight the importance of structural validation and in silico analysis towards determining the therapeutic potential of phage lytic proteins.
Periodontitis is a complex polymicrobial biofilm disease for which no targeted pharmacological therapies currently exist. Although Porphyromonas gingivalis is considered the keystone pathogen of periodontitis, how its synergistic interaction with the pathobiont Tannerella forsythia shapes biofilm community dynamics, host inflammatory responses, and bacterial gene expression remains largely unexplored. Using a five-species commensal biofilm model, we show that co-introduction of P. gingivalis triggers a greater than 10-fold increase in T. forsythia cell numbers, fundamentally restructuring the microbial community composition. Combined biofilm challenge induced upregulation of 47 genes in human periodontal ligament mesenchymal stromal cells, predominantly within the TNF and NF-κB signaling pathways, far exceeding inflammatory responses elicited by either pathogen alone. Strikingly, T. forsythia underwent sweeping transcriptomic remodeling in dual-species biofilms—upregulating nutrient acquisition systems, virulence factors, and lanthipeptide biosynthetic gene clusters—whereas P. gingivalis exhibited only minor transcriptomic changes. This asymmetric transcriptional response identifies T. forsythia as the primary responder to polymicrobial interaction and suggests that inter-species signaling drives a transition towards a more virulent T. forsythia phenotype. Collectively, these findings provide mechanistic support for the polymicrobial dysbiosis model of periodontitis pathogenesis and open new avenues for precision therapeutic intervention targeting inter-species synergy.
Climate change-driven increases in temperature and water scarcity pose major threats to agricultural productivity. The rhizosphere microbiome plays a central role in plant responses to abiotic stress and represents a promising target for improving crop resilience. Here, we investigated the rhizosphere microbiomes of four common bean (Phaseolus vulgaris L.) cultivars with contrasting drought tolerance under controlled water limitation. Using deep shotgun metagenomics, we constructed a rhizosphere gene catalog and recovered high-quality metagenome-assembled genomes to resolve taxonomic and functional profiles of the microbiome. Drought-tolerant genotypes were consistently associated with distinct quantitative microbial signatures, particularly enrichment of Actinomycetia and related functional pathways involved in osmoprotectant biosynthesis (e.g., trehalose, glycine betaine, and proline), oxidative stress mitigation, signal transduction, and nutrient cycling. Across genotypes, most genes and genomes were shared, indicating a stable core microbiome, while drought-tolerant cultivars showed a broader enrichment of stress-related taxa and functional traits within this shared background. These patterns suggest that drought primarily reshapes existing microbial functions rather than driving wholesale community replacement. Overall, our findings reveal genotype-dependent microbiome signatures associated with drought responses in common bean and provide a genome-resolved framework for identifying candidate taxa and functions for future validation. This study highlights the potential of microbiome-informed strategies to support crop resilience under water-limited conditions.
Corrosion imposes a $2.5 trillion annual global cost, with much attributed to microbiologically influenced corrosion (MIC) associated with sulfate-reducing bacteria (SRB). Existing mitigation strategies that rely on biocides or polymeric coatings are costly and ecologically disruptive. Here, we present a four-part framework integrating microbiome engineering, biological passivation, commensal antagonism, and sustainability. We define microbioclaim as a biologically mediated ecological dominance mechanism through which a commensal biofilm establishes protective control over the surface. Using copper (Cu) as a model metal, we show that Citrobacter sp. strain MICI21 forms a commensal biofilm that reduces SRB-induced corrosion in co-culture with Oleidesulfovibrio alaskensis strain G20. MICI21 conferred 3- to 15-fold higher resistance, and multimodal characterization confirmed formation of a compact MICI21-dominated biofilm that resisted sulfide ingress, limited pitting, and exhibited high rigidity (~0.8 GPa). Analyses indicate contributions from Cu–EPS interactions, competitive exclusion of SRB, and a putative Type VI secretion system (T6SS) associated with antagonistic potential in publicly available Citrobacter genomes. Complementary assays using isolated Citrobacter-derived extracellular polymeric substances (EPS), applied to bare copper surfaces in the absence of living cells, showed that EPS alone can contribute to surface passivation in 3.5% NaCl. Together, this work positions microbiome engineering as a design principle for living coatings.
The peri-implant microbiome is closely associated with dental implant health and disease, yet its development and genome-level dynamics remain insufficiently understood. In this longitudinal cohort, we performed shotgun metagenomics on 95 subgingival plaque samples from 19 participants, including peri-implant sites at weeks 1–4 after crown placement and adjacent teeth at week 1 as controls. Peri-implant and periodontal microbiomes showed distinct taxonomic and functional profiles, while shared taxa exhibited niche-related functional potentials, supporting selective assembly rather than fully passive translocation from adjacent sites. Longitudinal analysis identified microbiome development associated with three microbial modules, with distinct abundance and functional trajectories. Co-occurrence networks and generalized Lotka–Volterra simulations suggested that community context influenced colonization likelihood for specific taxa. At strain level, different microbial modules exhibited distinct extents of accumulative mutation, strain heterogeneity, and microevolutionary change. These findings provide a longitudinal framework of peri-implant microbiome succession and microevolution during early surface colonization.
Pulmonary fibrosis (PF) is a progressive interstitial lung disease with poorly understood mechanisms. Emerging evidence reveals that pulmonary microbiota dysbiosis serves as a critical link between environmental factors, host responses, and fibrotic progression. Microbial imbalance, increased bacterial burden, and altered metabolites contribute to PF through epithelial injury, immune–metabolic reprogramming, and signaling regulation. This review summarizes the multidimensional roles of the pulmonary microbiome in PF and explores its potential for therapy.
Mycotoxin contamination of feed and food, particularly with deoxynivalenol (DON), poses significant threats to intestinal health in livestock, yet the role of gut fungi (mycobiota) and fungal-bacterial interactions remains unclear. Across four piglet experiments integrating multi-omics and network analyses, we found that DON selectively disrupts the gut mycobiota, depleting the dominant yeast Kazachstania slooffiae and inducing a modular, competitive cross-kingdom network, while bacterial diversity remains intact. In contrast, AFB1 did not alter fungal composition, likely due to the immature mycobiota of suckling piglets, whereas antibiotic-associated diarrhea (AAD) caused bacterial collapse and a hyper-connected fungal network. Metatranscriptomics revealed that DON reprograms microbial activity toward virulence and detoxification at the expense of anaerobic metabolism, with coordinated downregulation of the microbial porA transcript (encoding pyruvate ferredoxin oxidoreductase) in Clostridium polysaccharolyticum and Methanobrevibacter, and suppression of butanoate metabolism and methanogenesis, supported by in silico predictions of direct DON-PFOR interaction. These transcriptional changes translated into reduced colonic butyrate and total short-chain fatty acids. Together, our findings establish a multi-kingdom framework for mycotoxin toxicity, positioning the mycobiota, particularly K. slooffiae and porA, as key ecological and molecular nodes linking dysbiosis to functional impairment with implications for mitigating DON-induced losses in livestock and improving global food safety.
Rheumatoid arthritis (RA) is associated with gut metabolite dysfunction, but the contribution of tryptophan-derived metabolites to RA remains fully uncharacterized. Here, we investigated the role of the gut microbiota-derived tryptophan metabolite indoleacrylic acid (IA) in experimental arthritis. Targeted metabolomics showed that fecal IA was markedly depleted in interleukin-1 receptor antagonist (IL1RA)-deficient and collagen-induced arthritis (CIA) mice. Oral administration of IA alleviated paw swelling, synovial hyperplasia, and cartilage destruction in both arthritis models. IA preserved intestinal barrier integrity by restoring ZO-1 and Occludin expression. In CIA mice, IA also reshaped the gut microbial community. In vitro, IA inhibited the proliferation and migration, promoted apoptosis, and suppressed inflammatory mediator production of fibroblast-like synoviocytes (FLSs). IA also inhibited M1 polarization and promoted M2 polarization of macrophages. Mechanistically, IA increased aryl hydrocarbon receptor (AhR) expression, and AhR silencing largely abolished its regulatory effects on FLS behavior and macrophage polarization. Transcriptomic analyses showed that IA suppressed necroptosis in FLSs by inhibiting RIPK1/RIPK3/MLKL signaling in an AhR-dependent manner. Collectively, these findings identify IA as a gut microbiota-derived metabolite with therapeutic potential in RA. The anti-RA effects of IA might involve coordinated regulation of the gut–joint axis, immune responses, and necroptotic signaling.
The gut microbiota is intricately linked to host phenotypes, yet its influence on host early growth and development, especially regarding the development of meat quality traits remains poorly understood. Here, we applied integrative multi-omics analyses of the gut microbiome, metabolome, and transcriptomes of muscle and colon tissues in Jinhua pigs during the rapid growth stage. At 90 days of age, Jinhua pigs exhibited a marked increase in microbial diversity, accompanied by enhanced microbial carbohydrate utilization and butyrate metabolism. To dissect host-microbe interactions, we integrated microbiome quantitative trait locus mapping with host whole-genome sequencing. Blautia wexlerae (B. wexlerae) emerged as a key microbial species genetically associated with multiple muscle related and meat quality traits. Colocalization and Mendelian randomization analyses implicated CPSF3 as a putative host gene potentially mediating the association of B. wexlerae on phenotypes such as loin muscle depth and lean meat percentage. Functional validation in mouse models showed that B. wexlerae supplementation was associated with improved muscle development, increased markers of type I muscle fibers, and attenuation of dexamethasone-induced muscle atrophy. B. wexlerae was associated with increased Ppargc1a expression in skeletal muscle, suggesting a potential role in muscle metabolism and fiber type specification. Overall, this study not only provides a promising avenue for enhancing pork quality through microbial interventions but also offers valuable insights for developing microbiota-based therapeutic treatments for human muscle related conditions such as sarcopenia and muscle atrophy.
Livestock farming is a major source of antibiotic resistance in the environment. Although supplementing selenium improves the GI-tract microecosystem and host metabolomes, nano-selenium effects on rumen microbiome and resistome remain limited. Here, multi-omics were performed to classify nano-selenium effects on rumen antibiotic resistance genes (ARGs) reduction, microbiome, metabolites, and host phenotypes on Hainan Black Goats. Increased growth performance, serum growth hormone, and antioxidant parameters by nano-selenium were observed. Nano-selenium significantly decreased the total ARG reads, MLS, and Tetracycline in the rumen. A strong correlation between the rumen resistome and microbiome was found. Nano-selenium increased the abundances of species of Prevotella and Fibrobacter. Moreover, nano-selenium enhanced carbohydrate metabolism and vitamin biosynthesis. Rumen fermentation parameters and metabolites related to carbohydrate utilization and antioxidant capacity were influenced by nano-selenium. Actinobacteria decreased by nano-selenium was associated with major ARGs related to Multidrug and Tetracycline. Structural Equation Modeling revealed that nano-selenium regulated MLS and Tetracycline for ARG reduction, and modulated the microbiome to improve rumen microbiome function. Overall, feeding proper concentrations of nano-selenium effectively reduces ARG pollution in vivo, and improves rumen microecosystem, growth, and antioxidant capacity in goats via microbiome modulation. These findings evidence that nano-selenium could benefit the goat industry, green food, and One Health.
Although gut microbiota-derived metabolites are increasingly implicated in host neuroendocrine regulation, it remains unresolved whether an orally delivered botanical can restore coordinated brain–gut homeostasis through a functionally supported microbiota-metabolite-endocrine pathway centered on a content-anchored, brain-accessible constituent. Here, using content-anchored pharmacometry in a chronic unpredictable mild stress (CUMS) model of depression with gastrointestinal (GI) hypomotility, we identified meranzin hydrate (MH) as the only absorbed prototype of Fructus Aurantii (FRA) detected in the brain and showed that, at its content-anchored dose, MH reproduced the major antidepressant-like and prokinetic effects observed with the parent botanical. Integrating 16S rRNA profiling, short-chain fatty acid (SCFA) quantification, plasma ghrelin, antagonist mapping, resting-state fMRI, serum-equivalent assays, and cross-tissue transcriptomics showed that MH reversed stress-disrupted microbial ecology, restored fermentative output, particularly butyrate, and re-established coupling between microbial metabolic function, circulating ghrelin, and synchronized brain-gut phenotypes. To directly test microbiota dependency, broad-spectrum antibiotic-mediated microbiota depletion was introduced, which markedly attenuated MH-associated recovery of SCFA output, plasma ghrelin levels, depressive-like behavior, and GI motility. Importantly, exogenous sodium butyrate did not restore bacterial biomass but partially rescued ghrelin levels and downstream phenotypes under microbiota-depleted conditions, supporting a microbiota-dependent butyrate-ghrelin mechanism rather than a purely correlative ecological association. Downstream, GHSR1a blockade disrupted this recovery hierarchy, whereas transcriptomic convergence analysis identified a shared contractile-immune host response program across the hippocampus and stomach. Collectively, these findings identify MH as a pharmacologically important, content-anchored contributor to FRA efficacy and provide functional perturbation-and-rescue evidence supporting a microbiota-dependent butyrate-ghrelin interface that contributes to coordinated brain-gut recovery under chronic stress.
Microbiome-gut-brain axis research largely focuses on high-income countries, leaving other populations reliant on findings that may not generalise to their contexts. To address this gap, we reanalysed 171,846 faecal samples profiled via amplicon sequencing from 72 countries to create the first global-scale characterisation of the human gut microbiome’s neuroactive potential. After inferring the genomic content of each sample, we found regional differences in the abundance of pathways for short-chain fatty acids, tryptophan, and GABA metabolism, as well as in the overall neuroactive potential of the human gut microbiome. Our results highlight a pressing need for greater global representation in the field.
Mobile genetic elements are major drivers of microbial niche development. The pheromone-responsive plasmid pCF10 enhances virulence of Enterococcus faecalis. Previously, we showed that pCF10 induces organized complex biofilm structures containing aggregated bacteria in the commensal strain OG1RF. Exposure to 100× the MIC of erythromycin (100× Erm) rapidly doubled both bacterial numbers and structure size. Here, we show that these structures form under flow and in chemostats, conditions relevant to infection, and nonattached biofilm aggregates were formed. Aggregation substance was required for complex structure formation and resistance to 100× Erm. Redox staining revealed elevated hydrogen peroxide (H2O2) within the structures. Catalase inhibited complex structure formation, consistent with our published mathematical model predicting a stress signal for spatially organized growth. pCF10 increased tolerance to H2O2. Exogenous H2O2 increased pCF10 copy number from ~3 to ~10 per cell, whereas cysteine-to-alanine substitutions in conserved cysteine residues of the replication initiation protein PrgW abolished this response. Erythromycin-induced population expansion persisted for at least 15 h, and clinically relevant subinhibitory and 1× Erm increased population and structure size. Mechanically disrupted biofilms were antibiotic sensitive, revealing some persisters. Mathematical simulations revealed spatial arrangements of aggregated structures capable of generating protected microenvironments enabling continued survival during antibiotic exposure.
Daily oscillations generated by the host circadian clock, together with rhythmic processes arising from the gut microbiota, form an integrated temporal framework that shapes digestive physiology. The host circadian clock shapes the gastrointestinal landscape through coordinated regulation of feeding patterns, epithelial renewal, immune surveillance, and bile acid metabolism. In turn, the gut microbiota generates rhythmic metabolites that provide reciprocal feedback to epithelial, metabolic, and immune pathways, further reinforcing circadian organization. Disruption of this bidirectional alignment, whether caused by altered light exposure, irregular eating patterns, genetic variation, or lifestyle-induced circadian misalignment, can fragment microbial oscillations, weaken mucosal resilience, and increase susceptibility to inflammatory, metabolic, and malignant digestive disorders. In this Review, we synthesize emerging insights into the molecular architecture that coordinates host and microbial rhythms and examine how its breakdown contributes to gastrointestinal disease. We also discuss chronobiological interventions, including feeding schedules, pharmacological timing, and microbiota-targeted strategies, that aim to restore temporal alignment. Viewing time as a critical functional dimension of host-microbiota biology provides a conceptual foundation for advancing precision diagnostics and therapeutics in digestive health.
Menopause is accompanied by skin changes, including complaints of itch, redness, and dry skin, linked to epidermal thinning and reduced sebaceous gland activity. These changes can cause microbiome dysbiosis, leading to dermatoses. Malassezia, a ubiquitous, lipid-dependent, and dominant skin fungus, is associated with multiple skin and systemic diseases. However, the mechanism for its pathogenicity in the context of host physiological changes, such as menopause, remains unexplored. We investigated the skin metagenomes of 345 Asian women spanning pre-, peri-, and post-menopause, revealing menopausal stage-specific differences in prevalence and abundance of Malassezia species. In keratinocyte co-culture, Malassezia elicited cytotoxicity beyond a critical fungal threshold, invaded keratinocytes, and induced inflammation. Transcriptomic profiling of keratinocytes exposed to toxic fungal loads revealed a gene expression profile characteristic of the hyperproliferative and undifferentiated phenotype present in many inflammatory dermatological diseases. Our findings reveal a mechanistic link between menopause-driven changes in skin physiology and Malassezia-mediated keratinocyte dysfunction.
