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Intestinal microbiome profiles in broiler chickens raised without antibiotics exhibit altered microbiome dynamics relative to conventionally raised chickens.

The present study was undertaken to profile and compare the cecal microbial communities in conventionally (CONV) grown and raised without antibiotics (RWA) broiler chickens. Three hundred chickens were collected from five CONV and five RWA chicken farms on days 10, 24, and 35 of age. Microbial genomic DNA was extracted from cecal contents, and the V4-V5 hypervariable regions of the 16S rRNA gene were amplified and sequenced. Analysis of 16S rRNA sequence data indicated significant differences in the cecal microbial diversity and composition between CONV and RWA chickens on days 10, 24, and 35 days of age. On days 10 and 24, CONV chickens had higher richness and diversity of the cecal microbiome relative to RWA chickens. However, on day 35, this pattern reversed such that RWA chickens had higher richness and diversity of the cecal microbiome than the CONV groups. On days 10 and 24, the microbiomes of both CONV and RWA chickens were dominated by members of the phylum Firmicutes. On day 35, while Firmicutes remained dominant in the RWA chickens, the microbiome of CONV chickens exhibited am abundance of Bacteroidetes. The cecal microbiome of CONV chickens was enriched with the genus Faecalibacterium, Pseudoflavonifractor, unclassified Clostridium_IV, Bacteroides, Alistipes, and Butyricimonas, whereas the cecal microbiome of RWA chickens was enriched with genus Anaerofilum, Butyricicoccu, Clostridium_XlVb and unclassified Lachnospiraceae. Overall, the cecal microbiome richness, diversity, and composition were greatly influenced by the management program applied in these farms. These findings provide a foundation for further research on tailoring feed formulation or developing a consortium to modify the gut microbiome composition of RWA chickens.

Animals

Long-term microbiome and clinical effects of a microbiome-guided personalized diet versus low-FODMAP diet in irritable bowel syndrome: A 12-month follow-up randomized controlled trial.

Dietary therapy is central to irritable bowel syndrome (IBS) management, yet the long-term durability of the low-FODMAP diet (LFD), and of microbiome-guided personalization, remains unclear. We assessed the long-term clinical and gut-microbiome effects of a microbiome-guided personalized diet (PD) compared with a standard LFD in adults meeting Rome IV criteria for IBS. In this multicenter, open-label randomized controlled trial with blinded outcome assessment, participants who completed a 6-week dietary intervention (PD or LFD) were followed at 6 and 12 months without further dietary intervention. Outcomes included the IBS Severity Scoring System (IBS-SSS), IBS Quality of Life (IBS-QOL), and the Hospital Anxiety and Depression Scale (HADS); gut microbiota were profiled by 16S rRNA sequencing. Longitudinal changes were evaluated using linear mixed-effects models, responder analyses, PERMANOVA, and PERMDISP. Both diets reduced IBS-SSS at 6 weeks. PD maintained symptom improvement at 6 and 12 months (-82.0 and -78.3 points from baseline), whereas LFD benefits regressed by 12 months (+29.3 points; between-group p&#x2009;=&#x2009;0.001). At 12 months, IBS-SSS responder rates were higher with PD than LFD (62.5% vs 34.5%; absolute risk difference&#x2009;+28.0%, 95% CI 4.2-47.7; Fisher p&#x2009;=&#x2009;0.029), and IBS-QOL, HADS-anxiety, and HADS-depression showed more favourable trajectories with PD. PD was associated with sustained Shannon alpha-diversity gains (+0.488 at 6 weeks;&#x2009;+0.205 at 12 months; both p&#x2009;<&#x2009;0.01). A modest between-group beta-diversity difference at 6 months (R2&#x2009;=&#x2009;0.035; p&#x2009;=&#x2009;0.011) was not significant at 12 months. This hypothesis-generating follow-up suggests more durable benefit with PD; larger trials powered for long-term clinical and microbiome outcomes are warranted.

Humans

Multi-level aggregation analysis of microbiome composition and host gene expression reveals associations with systemic and local immunity.

The human gut microbiome plays a critical role in immune regulation, yet the molecular links between microbiome composition and host gene expression remain incompletely understood. We analyzed associations between host gene expression and microbiome composition in a cohort of 315 healthy individuals, integrating microarray-based gene expression data from three intestinal sites (ileum, transverse colon, and rectum) and six immune cell types with microbiome sequencing data. Using a hierarchical feature aggregation strategy combining principal component analysis, clustering, and covariate correction, we discovered significant associations primarily related to immunity. While microbial profiles were similar across the three intestinal sites, the transverse colon yielded the most "microbiome-host gene expression" associations. Among the immune cell types, CD8+ cells showed the highest number of associations. The first principal component of microbiome composition, reflecting a gradient from commensals (e.g., Ruminococcaceae and Christensenellaceae) to proinflammatory taxa ([Ruminococcus] gnavus and Lachnoclostridium), correlated with the expression of TNF-&#x3b1;-linked genes (HMOX1, CPI17, HSD3B2, and SLC5A1). Among individual genera, Catenibacterium abundance was associated with gene expression in both intestinal and immune cells, including negative associations with MRPS21 (related to mitochondrial function) in the transverse colon and with CD8+ gene programs related to T cell differentiation. These findings align with emerging evidence implicating mitochondrial dysfunction in intestinal inflammation. Our results identify multi-level associations between the gut microbiome and host gene expression, suggesting potential mechanisms by which microbiota shape local and systemic immunity and vice versa. The implicated genes and taxa represent candidates for experimental validation to improve understanding of host-microbiome homeostasis and its disruption in disease.IMPORTANCEThe gut microbiome and immune system are engaged in a complex interplay throughout human life. While most associative studies focus on case-control comparisons-typically examining patients with conditions such as inflammatory bowel disease or metabolic diseases-less is known about the molecular links between the microbiome and immune system in healthy individuals. In this study of a large cohort of healthy individuals, we addressed this gap by applying multiscale modeling to tackle the high dimensionality of host-microbiome data. We identified multi-level associations between microbiome composition and host gene expression in both intestinal tissues and immune cells. These findings offer a valuable reference for understanding baseline host-microbiome communication and highlight molecular candidates-such as TNF-&#x3b1;-related genes and mitochondrial pathways-for future experimental validation.

Humans

Resistome and microbiome-immune interactions in an Eastern European population with high antibiotic use.

The gut microbiome influences host health, affecting gastrointestinal, metabolic, immune, cardiovascular, and neurological functions. A balanced microbiome is associated with favorable health outcomes. However, excessive antibiotic use and dietary habits can disrupt this ecosystem, leading to dysbiosis and affecting body homeostasis. This first comprehensive metagenomic analysis of the gut microbiome in a healthy Romanian cohort, a population underrepresented in microbiome studies and characterized by high antibiotic consumption, addresses a gap in current microbiome research. We report an enrichment of Enterobacteriaceae although overall composition is more comparable to other European than non-European cohorts. Community configurations align with established enterotype patterns, and our analysis provides insight into their relationship with within-phylum diversity. The analysis of antimicrobial resistance provides insight into the prevalence of resistance genes within this reservoir. We specifically report the presence of cfr(E), a Clostridioides difficile gene, and tet(X5), a variant from the ubiquitous tet family, genes not previously reported in healthy European populations. Integration with data from the European Centre for Disease Prevention and Control links the overall prevalence of resistance genes in this reservoir to antibiotic classes with higher community consumption in this population, notably beta-lactams and quinolones, highlighting potential targets for antibiotic stewardship programs. Finally, we investigate the relationship between the microbial profile and the systemic immune responses, inferred from correlations with in vitro cytokine production. Notably, we identify potential immune-priming roles for Collinsella, Flavonifractor, and Bifidobacterium species.IMPORTANCEThis first comprehensive study of the healthy gut microbiome in a Romanian cohort addresses a gap in current microbiome research, dominated by data sets from a limited number of regions. It sets a baseline for the microbiome and resistome composition of this population, and, while definitions of "healthy" microbiomes, or baseline resistomes, remain lacking, such study helps contextualize future studies and support the monitoring of dynamics. The Enterobacteriaceae abundance suggests a microbiome composition potentially influenced by antimicrobial consumption, a relevant pattern in a region with a high burden of nosocomial infections. In addition, the prevalence of antimicrobial resistance genes and the concordance with commonly used antibiotics in the community reinforce the need to address antibiotic use in public health strategies. Although gut microbiome-immunity relationships remain incompletely understood, our findings support a role for microbiome composition in immune-related traits and provide a valuable resource for future studies.

Humans

Metagenomic polymorphic toxin effector and immunity profiling predicts microbiome development and disease-related dysbiosis.

Bacteria use antagonistic interbacterial weapons, such as polymorphic toxin secretion systems (TSS), to compete for niches in the human gut microbiome. We hypothesized that TSS influence gut microbiome development and disease-related dysbiosis. We developed a bioinformatic marker gene approach (PolyProf) to quantify TSS including ~200 effector and immunity genes and applied it to ~15,000 publicly available human metagenomes. PolyProf alpha and beta diversity readily distinguished 12 different human disease states and enabled the construction of highly accurate linear regression classifier machine learning models. Elastic net machine learning models integrating bacterial taxonomy with PolyProf had strong predictive value for 12 disease states, outperforming models utilizing taxonomy alone. During microbiome development in the first year of life, PolyProf alpha diversity increases, and beta diversity becomes increasingly like the maternal microbiome, influenced by vertical transfer, delivery mode, and breastfeeding. PolyProf is related to strain sharing among adults through social interactions. In summary, TSS genes strongly correlate with microbiome development and interpersonal strain sharing, suggesting roles for interbacterial antagonism. Since PolyProf distinguishes diverse adult disease statuses, these dynamics may contribute to non-genetic inheritance.IMPORTANCEPrevious research has demonstrated that bacteria compete within the gut microbiome using toxin secretion systems (TSS). How TSS contribute to human microbiome development and the microbiome alterations observed in human diseases is not known. This study develops a new bioinformatic tool for profiling TSS-related genes in metagenomic data. Application of this approach to large-scale human fecal metagenomic data demonstrates the dynamic association of TSS during microbiome development, including the exchange of strains among social contacts. TSS gene abundance patterns are highly predictive of 12 disease states. This study advances the field by enabling TSS profiling in metagenomes and by identifying disease and microbiome development biomarkers that provide hypotheses for future mechanistic studies and may be useful for disease diagnosis.

Dysbiosis

Unveiling Potato Cultivars With Microbiome Interactive Traits for Sustainable Agricultural Production.

Root traits significantly shape rhizosphere microbiomes, yet their interaction with microbes is often overlooked in plant breeding programs. Here, we propose that selecting modern cultivars based on microbiome interactive trait (MIT), such as root biomass, exudate patterns and the rhizosphere microbiome, can enhance agricultural sustainability by interacting effectively with soil microbiomes, which in turn, promotes plant growth and resistance to stress, thereby reducing reliance on synthetic crop protectants. Through a stepwise selection process (in silico and in vitro) that started with approximately 1000 potato genotypes, we chose 51 potato cultivars based on known phenotypical properties and distinct root exudate patterns. We conducted a greenhouse experiment to evaluate their capacity to interact with the soil microbiome and to assess their MIT scores. Our findings revealed that cultivars significantly influence plant growth, metabolite profiles, and rhizosphere fungal community composition. Moreover, we observed a positive correlation between microbial community diversity and root biomass. Additionally, leaf metabolites were correlated with rhizosphere bacterial composition, supporting the plant holobiont framework. Utilising z-scores, we aggregated all data related to plant growth, metabolomes, and microbiomes, creating a classification of 51 cultivars based on a gradient of MIT scores. By examining the distribution of low, intermediate, and high MIT, we identified a group of 11 potato cultivars suitable for further studies to assess their resilience and productivity under low-input production systems. This study provides an in-depth correlation between microbiome and several plant traits across 51 cultivars, offering tools to facilitate and expedite the incorporation of microbiome traits into breeding goals to support sustainable agriculture.

Solanum tuberosum

Microbiome therapeutic PMC101 inhibits the translocation of carbapenem-resistant Klebsiella while enhancing eubiosis in antibiotic-induced dysbiosis mice.

Carbapenem-resistant Enterobacteriaceae (CRE), known for their extensive antibiotic resistance, pose a severe global medical threat. Therefore, developing novel therapeutics beyond conventional antibiotics is urgently needed, and the importance of microbiome therapeutics is increasingly being recognized. This study explores the expanded systemic efficacy of PMC101, a microbiome therapeutic, beyond intestinal CRE infections and investigates its mechanism of action from a microbiome perspective. First, the genetic characteristics of the novel strain were identified through whole-genome analysis, and a scalable cultivation process was established as part of the overall development of this microbiome therapeutic. PMC101 increased the survival rate to 100%, significantly reduced disease severity scores, and prevented weight loss in CRE-infected mice treated with antibiotics. These effects are attributed to the inhibition of CRE growth in stool and the reduced detection of CRE in the lungs and kidneys, indicating suppression of systemic translocation. Metagenomic analysis revealed that PMC101 prevented the reduction in microbial population caused by antibiotics and CRE infection, restored species diversity indices, and mitigated dysbiosis while promoting eubiosis. This CRE translocation suppression was closely associated with increased CRE translocation-microbiome index, defined as the ratio of Bacteroidetes to Proteobacteria. This relationship was further confirmed through simulations using a human intestinal microbial ecosystem model. Additionally, increases in short-chain fatty acids, reductions in excessive inflammatory responses, and decreases in tissue damage were observed, all of which contribute to preventing CRE translocation. Finally, pathogen inhibition effects and safety tests were conducted, confirming the prophylactic potential of PMC101 as a microbiome therapeutic. These findings strongly support PMC101 as a promising candidate for future microbiome-based therapies against CRE infections.

Animals

Metaproteomic Analysis to Assess the Impact of Storage Media on Human Gut Microbiome in Fecal Samples.

The human gut microbiome is a diverse community of microorganisms residing in the gastrointestinal tract. The storage condition of fecal samples may impact the taxonomic and protein compositions of microbiomes in these samples. Here, we performed a mass spectrometry-based metaproteomic study to assess the impact of storage media on human gut microbiome in fecal samples. We evaluated FDA-authorized OMNIgene&#xb7;GUT (OG), phosphate-buffered saline (PBS), and RNALater (RNAL) buffers and identified 38,185 microbial peptides corresponding to 7348 microbial proteins, which matched 16 phyla, 20 classes, 50 orders, 104 families, 332 genera, and 453 species. We found a high similarity among the fecal microbiomes preserved in OG, PBS, and RNAL in terms of the identification of proteins, taxa, and functional annotations. Both alpha and beta diversity suggested the high similarity among samples stored in the three media. Nonetheless, we also found some notable differences among buffers regarding the abundances of a few taxon groups. A partial human proteome (over 400 proteins) was identified in the fecal samples, with most of these proteins associated with the membrane and extracellular regions. The findings indicate the similarity among microbiomes in the fecal samples stored in OG, PBS, and RNAL regarding proteome profile, taxa, and functional capacity. SUMMARY: This study thoroughly analyzed and compared the metaproteomes of fecal samples preserved at -80&#xb0;C in PBS, RNALater, and OMNIgene&#xb7;GUT Dx buffers, offering novel insights into the effectiveness of these buffers in maintaining the stability and composition of the human gut microbiome. We found a high similarity in the identification and quantification of proteins, taxa, and functional annotations across the three buffers, with notable quantitative differences highlighting subtle yet important variations in preservation efficacy. The unique datasets and findings could offer valuable revelations into the impact of fecal sample preservation on translational and clinical analyses of the human gut microbiome.

Humans

Resistant starch types 2 and 4 induce distinct and reversible changes in the human gut microbiome.

Resistant starch (RS) can confer benefits for the gut microbiome and host cardiometabolic health. However, different types of resistant starch can differentially affect gut microbiome composition and functional capacity, especially given interindividual variability in responses, thus limiting the application of resistant starch in dietary strategies. We used shotgun metagenomics to perform a secondary analysis of samples collected during a previously reported randomized clinical trial to determine the effects of dietary supplementation with two types of resistant starch (RS2 and RS4) and a digestible starch (control) on the gut microbiome. Both resistant starch types induced distinct but transient alterations in the gut microbial community. RS2 enriched the keystone degrader, Ruminococcus bromii, and Blautia glucerasea, whereas RS4 favored Parabacteroides distasonis and known but uncharacterized microbial species such as a Lachnospiraceae bacterium. Moreover, we detected strain-level differences in the response of Bifidobacterium adolescentis to resistant starch. Microbial functional profiling revealed an enhanced capacity for complex carbohydrate utilization following resistant starch intake, including increased abundance of specific &#x3b1;-amylases, glycoside hydrolases, starch utilization systems, and other currently uncharacterized genes. Identifying the bacterial strains and genes that respond to different RS types will help to more accurately predict who will benefit from a given RS type. Our findings demonstrate that RS2 and RS4 differentially shape microbial ecology and metabolic capacity and provide a foundation for microbiome-informed personalization of resistant starch-based dietary interventions.IMPORTANCEDietary intake influences human health by modulating metabolism, partly by shaping the microbiota inhabiting the gut. Resistant starch (RS), a dietary fiber, is associated with metabolic improvements. While previous research has explored how RS alters the gut microbiome, RS comprises five types with differing physical and chemical characteristics, and the distinct impacts of each type on the microbiome and host health have not been fully characterized, particularly using high-resolution approaches such as shotgun metagenomics. In this secondary analysis of samples from a longitudinal crossover intervention study, we link dietary supplementation with RS2 and RS4 with distinct and transient changes in the composition and functional potential of the human gut microbiome. Specifically, we identify species that increase in abundance with each RS type, accompanied by increases in genes and pathways involved in complex carbohydrate utilization. The findings support the development of precision nutrition strategies utilizing RS supplementation to improve metabolic health.This study is registered with ClinicalTrials.gov as NCT05743790.

Humans

From sporulation to village differentiation: The shaping of the social microbiome over rural-to-urban lifestyle transition in Indonesia.

Despite established roles in human health and profound global diversity, microbiome datasets remain biased toward Western urban cohorts, with especial under-representation of Southeast Asia. Here, we present a gut microbiome dataset from 116 Indonesians spanning transitional hunter-gatherer, rural agricultural, and urban lifestyles. We identify 1,304 species and 3,258 subspecies by assembling 11,070 metagenome-assembled genomes, revealing substantial species- (15%) and subspecies- (50%) level novelty. Novel taxa are rare, often village specific, and depleted for sporulation genes, revealing a link between bacterial physiology, transmission, prevalence, and discovery. We identify rural-to-urban clines across multiple levels of biological organization, from species abundance to microbiome composition and diversity. Furthermore, between-community, but not within-community, diet variation is strongly predictive of microbiome composition, suggesting that microbiome divergence is driven by community-level differences. Our work highlights the interplay of host lifestyle, population structure, and bacterial physiology in shaping microbiome diversity and biogeography, at the key scale of human communities.

Humans

Ecological Filtering by Tuber Compartments Shapes Stable Core Microbiomes That Underpin Potato Plant Growth Across Environments.

Harnessing plant microbiomes for sustainable agriculture requires understanding not only whether they can boost crop performance, but also how ecological processes govern their assembly, stability, and functional contributions across environments. While we previously showed that seed tuber microbiomes can predict potato vigour using machine learning, it remained unclear how ecological processes shape tuber microbiome stability and functionality across host genotypes, tuber compartments, soil types, and years. Here, we analyzed the national-scale dataset of 240 field-collected potato seedlots, spanning six genotypes, two soil types, and two growing years, with a focus on the spatially distinct heel and eye compartments of the potato tuber. By profiling over 1200 bacterial and fungal communities and linking microbiome composition to plant performance, we show that plant genotype and tuber compartment are the strongest determinants of microbial diversity and composition. Compartment-specific enrichment of functional traits revealed spatial partitioning of microbial functions, with organic compound conversion and nitrogen cycling dominant in the heel, and energy metabolism enriched in the eye. Applying a macroecological abundance-occupancy framework, we identified a stable core microbiome of bacterial and fungal taxa that persisted across all environments and years. These core members were more strongly associated with plant growth-related traits than non-core taxa, and core taxa in different tuber compartments showed distinct correlations with taxa of potential pathogenic relevance. Together, our findings demonstrate that tuber compartments act as ecological filters that structure persistent, functionally specialised microbiomes linked to plant growth-related traits across environments. By providing an ecological and functional framework for compartment-resolved, stable core microbiomes, this study advances mechanistic understanding of plant-microbe interactions and identifies stable microbial partners as promising targets for improving potato resilience and productivity.

Journal Article

High dietary fiber is associated with improved outcomes in patients with melanoma and sarcoma treated with immunotherapy regardless of gut microbiome dysbiosis and social vulnerability.

BACKGROUND: Social vulnerability, dietary fiber, and the gut microbiome have been individually implicated in clinical outcomes for melanoma and sarcoma patients. This study hypothesized that increasing social vulnerability is associated with insufficient dietary fiber intake and negatively associated with microbiome composition and clinical outcomes. METHODS: Clinicopathologic data, baseline fiber intake, and gut microbiome profiles were assessed in 153 patients with melanoma or sarcoma treated with immune checkpoint blockade (ICB) and prospectively followed. Patients' social vulnerability index (SVI) and fiber intake were evaluated for associations with microbiome composition, treatment response, and overall survival (OS). RESULTS: SVI percentile was 0.4 (interquartile ratio [IQR], 0.2-0.7), and median dietary fiber intake was 17 (IQR, 15-20) g/day. SVI was inversely correlated with dietary fiber intake (r, -0.18, p&#xa0;=&#xa0;.0398). Gut microbiome analyses revealed community and compositional differences by SVI, including inverse associations with &#x3b1;-diversity and the relative abundance of favorable bacteria such as Bifidobacterium longum (p&#xa0;<&#xa0;.001), contrasting the positive associations observed between fiber and these microbial markers. Increased dietary fiber intake was associated with measurable response to ICB. A difference in OS was not observed in more socially vulnerable patients (SVI, not reached vs. 81.7 months), however, a survival advantage was evident with higher dietary fiber intake (not reached, 58.9 months). CONCLUSIONS: Increased social vulnerability was associated with a less favorable gut microbiome composition but not worse OS among melanoma and sarcoma patients treated with ICB. Consistent with prior findings, high dietary fiber intake emerged as a potentially modifiable pathway to improve outcomes in patients initiating ICB, particularly those with increased SVI.

Humans

Temporal stability and lack of variance in microbiome composition and functionality in fit recreational athletes.

Human gut microbiome composition and function is influenced by environmental and lifestyle factors, including exercise and fitness. We studied the composition and functionality of the faecal microbiome of recreational (non-elite) runners (n&#x2009;=&#x2009;62) with serial shotgun metagenomics, at 4 time points over a 7-week period. Gut microbiome composition and function was stable over time. Grouping of samples on the basis of their fitness level (fair, good, excellent, and superior) or habitual training (low (4-6&#xa0;h/week), medium (7-9&#xa0;h/week), high (10-12&#xa0;h/week), and extreme (13&#x2009;+&#x2009;hours/week)) revealed no significant microbiome-related differences. Overall, the species Faecalibacterium prausnitzii, Blautia wexlerae, and Prevotella copri were the most abundant members of the gut microbiome. Analysis of co-abundance groups (CAGs) revealed no significant relationship between CAGs and fitness levels or training subgroups. Functional pathways were similar across all samples and timepoints with no clustering based on associated metadata. The most abundant genes identified within samples corresponded to pathways for nucleoside and nucleotide biosynthesis, amino acid biosynthesis, and cell wall biosynthesis. Collectively, these results describe the microbiome of active recreational runners and note temporal stability amongst participants.

Humans

Spatial scaling of metagenomic diversity reveals ecological disruption in the gut microbiome of gout patients.

Gout, a painful inflammatory arthritis, is characterized by hyperuricemia and monosodium urate crystal deposition, with growing evidence linking its pathogenesis to gut microbiome dysbiosis. However, traditional diversity metrics fail to capture the complex spatial organization of microbial communities. This study addresses this gap by applying the novel metagenomic Diversity-Area Relationship (m-DAR) model to investigate scaling laws in the gout microbiome-quantifying how metagenomic diversity changes with the number of individuals sampled. Our analysis of gut microbiomes from gout patients and healthy controls revealed fundamental ecological disruptions. We found that gout microbiomes exhibited significantly altered scaling patterns: they showed greater inter-individual dissimilarity (higher z-values) at the level of rare genes (q&#x2009;=&#x2009;0), but weaker scaling of dominant genes (q&#x2009;=&#x2009;1-3) compared to healthy controls. Crucially, the maximal accrual diversity (MAD) was substantially lower in gout patients, indicating a severely constrained potential for total microbial gene diversity. Furthermore, profiling of metagenomic functional gene clusters (MFGCs) uncovered widespread functional perturbations, including increased diversity scaling for carbohydrate-active enzymes (CAZy) but decreased scaling in essential metabolic pathways (KEGG, KO). These results demonstrate that the gout gut microbiome is defined by a loss of ecological structure, featuring reduced homogeneity in dominant taxa, expanded rare biosphere variation, and an overall collapsed diversity capacity. This work introduces an ecological framework for characterizing dysbiosis in gout that complements traditional diversity metrics and may inform the development of microbiome-based therapeutic strategies. Further research is needed to translate these ecological patterns into clinical applications.

Humans

A randomized controlled trial to unveil the influence of an exercise intervention on brain integrity and gut microbiome structure in individuals with HIV.

OBJECTIVE: Exercise intervention programs enhance physical fitness, cognition, neuroimaging measures, and alter the structure of the gut microbiome in individuals without HIV. However, interventional studies exploring the effects of exercise in persons with HIV (PWH) have not included neuroimaging or gut microbiome analyses. DESIGN: A randomized controlled trial conducted at Washington University in St. Louis, MO, USA. METHODS: 65 PWH (aged &#x2265;40&#x200a;years, self-reported sedentary lifestyle) were randomly assigned to a 6-month cardiorespiratory and resistance training (EXS) or stretching control (SIS) intervention in a 2&#x200a;:&#x200a;1 ratio. Longitudinal change in cognition, cerebral blood flow (CBF), physical and cardiorespiratory fitness, and gut microbiome diversity and composition were examined among participants ( n &#x200a;=&#x200a;62) who completed any portion of the intervention (ClinicalTrials.gov: NCT02663934). RESULTS: Better fitness and better cognitive performance were associated with greater phylogenetic diversity in gut microbiome composition at baseline. Longitudinal findings indicated slight but significant improvements in psychomotor speed and executive function, reductions in body mass index, improvements in physical fitness, and increased gut microbiome diversity. These changes were observed regardless of assigned intervention group. There were no observed changes in CBF for either group. CONCLUSIONS: These findings highlight physical fitness as a modifiable factor in PWH that may improve cognitive performance and change gut microbiome composition. Both interventions were beneficial, suggesting light stretching exercise or study participation alone could have been sufficient to introduce positive cognitive shifts in previously sedentary PWH. Longer interventions with more participants are needed to identify changes in neuroimaging metrics related to brain integrity.

Humans

Maternal contact and age-dependent succession influence the assembly of the calf rumen microbiome and virome.

Early-life colonization of the rumen is particularly important; however, the processes by which microbial and viral communities are transmitted and developed remain poorly understood. Here, we present a genome-resolved investigation of the effects of maternal contact and age-dependent succession on the calf rumen microbiome and DNA virome by comparing calves raised with or without maternal contact across early life using the metagenome-assembled genomes (MAGs) and viral operational taxonomic units (vOTUs) reconstructed from whole- and virus-like particle metagenomes. Across longitudinal samples from calves and their mothers, we identified 694 MAGs and 30,479 vOTUs, substantially expanding current genome databases and revealing extensive microbial and viral novelty. Our analyses demonstrated that both prokaryotes and DNA viruses are shared between dams and calves, with greater sharing observed in calves raised with maternal contact than in calves raised without maternal contact. Notably, viral sharing between cow-calf pairs was markedly lower compared to prokaryotes, suggesting high turnover and rapid viral diversification. Age-associated analyses further revealed coordinated shifts in prokaryotes and their viruses, with dominant genera such as Prevotella, Ruminococcus, and Fibrobacter, and their corresponding viruses increasing after day 40. These findings indicate that the early-life rumen microbiome and DNA virome undergo substantial age-dependent succession and are associated with maternal contact, providing new insights into host-microbe-virus interactions during rumen development.IMPORTANCEThis study provides one of the first genome-resolved views of DNA viral community development during early rumen colonization in calves (from 1 week to 70 days of age) and reveals how maternal contact and age influence the establishment of the calf rumen microbiome and virome. By analyzing longitudinal samples from calves raised with or without their mothers, we show that prokaryotes and their viruses undergo coordinated, age-dependent succession. Our results demonstrate that maternal separation alters the assembly of the calf rumen microbiome, highlighting the influence of maternal contact during early-life rumen development. These findings underscore the high plasticity of the early-life rumen ecosystem and suggest that early management practices, such as maternal separation, can have lasting effects on rumen development. This work provides fundamental insights into the establishment and succession of the calf rumen microbiome and DNA virome during early life and may contribute to future microbiome manipulation studies.

Animals

A high-quality genomic catalog of the human oral microbiome broadens its phylogeny and clinical insights.

The oral microbiome is increasingly linked to human health. To further examine this microbial community, we present the human reference oral microbiome (HROM), with 72,641 high-quality genomes from 3,426 species, including 2,019 previously unidentified species, improving metagenomic sequence read classification over existing catalogs. Notably, HROM unveils 1,137 previously uncharacterized candidate phyla radiation (CPR) species, establishing Patescibacteria as the most prevalent phylum in the oral microbiota and distinct from environmental Patescibacteria. Additionally, an oral CPR subclade is associated with periodontitis, complementing Porphyromonas gingivalis in predicting disease. Finally, comparing HROM with reference genomes of the gut microbiome reveals taxonomic and functional divergence between these microbiomes. HROM contains 42 ectopic oral species, and their relative abundance in gut microbiota is predictive of intestinal, cardiovascular, and liver diseases. Thus, HROM offers an expanded view of the oral microbiome and highlights the clinical importance of further examining the links between oral microbes and systemic disorders.

Humans

Alterations of gut microbiome in chronic rhinosinusitis: insights from a mendelian randomization study.

OBJECTIVE: Gut microbiome dysbiosis is associated with various diseases. Causal association between Chronic Rhinosinusitis (CRS) and gut microbiome is yet unknown. This study aimed to investigate the potential causal relationship between CRS and gut microbiome dysbiosis. METHODS: We used Genome-Wide Association Study (GWAS) data from FinnGen database for CRS. The Dutch Microbiome Project study provided data on gut microbiota species. A total of 334,182 individuals were included. Two-sample bidirectional Mendelian Randomization (MR) analysis was used to investigate causal relationship between CRS and gut microbiome. The main methods of evaluation were Inverse Variance Weighting (IVW), weighted median, weighted mode, and MR-Egger regression. Sensitivity analyses were performed to assess heterogeneity and pleiotropy. RESULTS: Forward MR analysis indicated CRS is potentially linked to decreased risk of Haemophilus parainfluenzae (OR = 0.79, 95% CI 0.66&#x2012;0.94, p = 0.009) and increased risk of Bilophila's (OR = 1.14, 95% CI 1.02-1.27, p = 0.023) within the gut. Reduced risks in gut microbiota-related pathways like UDP-N-acetyl-d-glucosamine biosynthesis I (OR = 0.85, 95% CI 0.77&#x2012;0.94, p = 0.002) and increased risk in pathway NAD biosynthesis I from aspartate (OR = 1.14, 95% CI 1.03-1.27, p = 0.010) were also linked to CRS. Reverse MR analyses, we obtained no positive results (p > 0.05/412). CONCLUSION: This study reveals CRS exerts a causal impact on shifts within the composition of the gut microbiome and also links to the changes of gut microbiota-related metabolic pathways. The risk of changes in gut microbiota should be of greater concern in patients with CRS than in the general population. LEVEL OF EVIDENCE: Mendelian Randomized (MR) studies are second only to randomized controlled trials in terms of the level of evidence.

Humans