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PubMed2026

PREVENT 1, a nationwide Swedish infant cohort for longitudinal gut microbiome profiling and early-life health outcomes: cohort profile.

PURPOSE: PREVENT 1 is a nationwide, prospective Swedish infant cohort established to characterise gut microbiome development during the first 2 years of life and to relate microbial trajectories to feeding, infections, growth and everyday well-being. The study integrates repeated infant stool sampling with shotgun metagenomics analysis with aligned parental questionnaires, stool photographs and infant cry recordings collected at three approximately 3-month intervals for each infant. PARTICIPANTS: Families were recruited nationwide in Sweden from September 2023 through targeted digital channels. Eligible participants were term-born infants residing in Sweden and aged <1 year at enrolment. Baseline questionnaire data and stool samples were collected from 253 infants. Parents completed questionnaires covering socio-demographic characteristics and health, pregnancy and delivery, postnatal factors, infant environment, feeding and growth, infections and other health outcomes, gastrointestinal symptoms and everyday well-being. FINDINGS TO DATE: Retention was high, with 248 families completing at least one follow-up questionnaire at Phase 2 and 243 at Phase 3. For stool samples, 250 infants provided at least two samples and 241 provided all three. At enrolment, 42.3% of infants were older than 7 months, 73.9% had weight-for-length z-scores in the normal range and exclusive breastfeeding at 4&#x2009;months was reported for 58.9%. FUTURE PLANS: Three-phase sample and questionnaire data collection was completed in December 2024. Future analyses will examine microbiome features, resistome profiles and functional pathways in relation to antibiotic exposure, feeding, growth and infant health outcomes. Subject to ethical approval and participant consent, follow-up may include further stool collection and Swedish register linkage. TRIAL REGISTRATION NUMBER: NCT06285630.

Female↗
PubMed2025

Impact of RNA extraction on respiratory microbiome analysis using third-generation sequencing.

BACKGROUND: The respiratory microbiome, which comprises bacteria, fungi, and viruses, plays a crucial role in respiratory health and disease. However, its study is limited by the low microbial biomass in respiratory samples and the dominance of host RNA. Metatranscriptomics offers comprehensive insights into active microbial communities and their interactions with the host but requires optimized RNA extraction protocols for robust and unbiased analysis. This study evaluated two RNA extraction kits&#x2014;one employing chemical lysis (CL) and another combining chemical and mechanical lysis (CML)&#x2014;to determine their effectiveness for metatranscriptomic analysis of respiratory samples. RESULTS: The CML protocol significantly increased double-stranded DNA (dsDNA) library yields, leading to higher sequencing read counts for both sample types (p&#x2009;<&#x2009;0.0001). The read length was unaffected by the lysis protocol for the BAL and NPS samples. Taxonomic profiling revealed that CML enhanced the detection of robust microorganisms, such as gram-positive bacteria and fungi, without compromising viral detection. CONCLUSIONS: The CML protocol demonstrated superior recovery of genetic material, particularly for fungi and gram-positive bacteria, making it better suited for comprehensive metatranscriptomic analyses. These findings underscore the need for tailored RNA extraction strategies on the basis of sample type and research objectives. Optimized metatranscriptomic protocols are pivotal for advancing our understanding of the respiratory microbiome and its role in health and disease.

Microbiota↗
PubMed2026

Microbiome and resistome successions in pig carcasses and fresh pork meat throughout slaughtering, processing and shelf-life.

BACKGROUND: Slaughterhouses and meat cutting plants represent potential hotspots for the spread and transfer of spoilage and pathogenic, including antimicrobial resistant, bacteria to meat and meat products. Here, we characterise the progression of the microbiome and resistome of two pork cuts (loin and sirloin) at different stages of processing, from the slaughter line to the end of shelf-life. To this end, we analysed samples from facility surfaces, carcasses, and meat cuts using whole metagenome sequencing. RESULTS: The taxonomic and antimicrobial resistance gene (ARG) profiles of carcasses and meat cuts were significantly influenced by the point of sampling and the processing room. The facility surfaces were found to be the main source of some abundant genera, such as Anoxybacillus, Acinetobacter, Pseudomonas, and Brochothrix, in carcasses and meat cuts. A total of 1,291 metagenome-assembled genomes were reconstructed, corresponding to the most prevalent species identified in the taxonomic analysis at the read level. A reduction in bacterial and ARGs richness and diversity was observed for carcasses and meat cuts along the production chain, which suggests that processing procedures are effective in reducing bacterial and ARGs loads. Nonetheless, an increase in the ARGs load was observed at two sampling points: the carcass after evisceration and the sirloin at the end of its shelf-life (in this case linked to the increase of a single gene, tet(L)). The ARGs most frequently detected were those associated with resistance to tetracyclines, aminoglycosides, and lincosamides. Acinetobacter (in processing environments and carcass/meat samples) and Staphylococcus (in carcasses and meat) were identified as the main genera associated with the ARGs found. CONCLUSIONS: Overall, our results provide the most detailed metagenomics-based perspective on the microbial successions of pig carcasses and fresh meat cuts during slaughtering, processing, and commercialisation. The observations made suggest that selection pressures imposed by processing steps and contact with facility surfaces contribute to shaping the microbiome and resistome of the two pork products throughout their production line and shelf-life. Video Abstract.

Animals↗
PubMed2026

The antimicrobial gut resistome of the Wayampi reveals a shared background of antibiotic and metal resistance genes with industrialized populations, underscoring the "robust-yet-fragile" architecture of human gut microbiomes.

BACKGROUND: Metagenomics enables detailed profiling of genes encoding antimicrobial resistance. However, most studies focus exclusively on antibiotic resistance genes (ARGs), excluding those associated with non-antibiotic antimicrobials (metals, biocides), and often rely on methods with low-sensitivity and low-specificity. Furthermore, they rarely examine populations exposed to minimal anthropogenic pollution. We analyzed fecal resistomes of 95 Wayampi individuals, an Indigenous community in remote French Guiana, using a targeted metagenomic capture platform covering 8667 genes, including ARGs, metal resistance genes (MRGs) and biocide resistance genes (BRGs) (PMID: 29335005). Resistome profiles were compared with those of Europeans to assess population-level differences. RESULTS: ARG richness was similar between groups (259 in Wayampi vs. 264 in Europeans, 159 shared), but MRGs&#x2009;+&#x2009;BRGs gene richness was significantly higher in Wayampi (11,930 vs. 7419). Most genes appeared in a minority of individuals (mean 5% for ARGs, 2% for MRGs&#x2009;+&#x2009;BRGs), but several ARGs for tetracyclines [tet(32), tet(40), tet(O), tet(Q), tet(W), tet(X), tetAB(P)], aminoglycosides (ant6'-I, aph3-III), macrolides (ermB, ermF, mefA), and sulfonamides (sul2) were present in all individuals. Tetracycline resistance genes predominated overall, while beta-lactam resistance genes were more common in Wayampi, and genes conferring resistance to aminoglycosides, amphenicols, and folate inhibitors were more frequent in Europeans. Among MRGs, copper and arsenic resistance genes prevailed in both groups, followed by those for zinc, iron, cobalt, and nickel. Up to 76% of Wayampiis carried acquired MRGs for copper (pcoABCDRS and tcrB), silver (silACFPRS), arsenic (ars), and mercury (mer) detoxification. Shannon diversity indices were similar for ARGs, MRGs, and BRGs, but composition and evenness differed significantly. UMAP and ADONIS analyses distinguished cohorts based on ARG profiles (p&#x2009;<&#x2009;0.001), but not on MRGs or BRGs. Correlation analysis revealed conserved gene-sharing networks and introgression of acquired ARGs and MRGs within both gut microbiomes. CONCLUSIONS: The diverse and balanced Wayampi resistome reflects a less perturbed microbiome compared to industrialized populations, and reveals a background of "core" and "shell" acquired ARGs and MRGs, consistent with the "robust-yet-fragile" architecture of scale-free networks. The patchy yet resilient gene distribution suggests varying levels of conserved gene sharing highways among populations, likely shaped by long-term microbial-human evolution, and supports a broader view on acquired antimicrobial resistance. Video Abstract.

Humans↗
PubMed2026

Interconnected influences of diet, gut microbiome, and metabolome on cognition across three metabolomics platforms.

Cognitive impairment is increasing with global aging, yet mechanisms linking diet, the gut microbiome, and metabolism to cognitive function remain unclear. To investigate a diet-microbiome-metabolome axis associated with cognition, we integrated fecal metagenomics, diet, and multi-platform plasma metabolomics in 505 older adults from four ADRCs. Several microbes broadly associated with circulating metabolites were also linked to multiple measures of cognitive performance. These taxa exhibited coordinated metabolic signatures, with cognition-positive microbes associated with antioxidant, lipid, and microbial-host co-metabolites, and microbes negatively associated with cognition were linked to inflammatory and aromatic amino acid-derived metabolites. Dietary patterns, particularly the Healthy Eating Index Greens and Beans component, were associated with microbial composition and metabolomic structure. Mediation analyses supported a diet-microbe-metabolite-cognition pathway, while metabolites remained associated with cognition after accounting for microbial features. These findings highlight the metabolome as a central integrator of diet, microbial activity, and cognitive function.

Journal Article↗
PubMed2026

Genome-resolved analysis of colonization factor repertoires reveals ecological stratification in cervid gut microbiomes.

INTRODUCTION: Colonization factors (CFs) are important microbial traits associated with persistence and host adaptation in the gut, yet their large-scale organization in cervid gut microbiomes remains unclear. METHODS: A total of 3,311 non-redundant high-quality metagenome-assembled genomes (MAGs), derived from 688 cervid gut metagenomic samples across 15 publicly available projects and one in-house dataset, were analyzed. CF-associated genes were identified by comparison against the GHA CF database, and CF repertoires were characterized at genome, host-species, and gastrointestinal-segment levels. RESULTS: A total of 138,729 CF-associated genes spanning 71 CF families were identified. MAGs from Cervinae contained richer CF repertoires than those from Caprinae, and CF47 (Peptidase_C69), CF24_29 (QueH), and CF18 (Glycos_transf_2) were among the most prevalent families. CF repertoires were strongly structured by taxonomy, showed a moderate association with bacterial phylogenetic distance, and formed two recurrent genome-level configurations with distinct KEGG functional profiles. Integration of sample metadata further revealed differentiation of CF repertoires across host species and gastrointestinal segments, representing the major ecological dimensions examined in this study. Segment-associated CF variation was accompanied by redistribution of broader functional profiles, including enrichment of carbohydrate and lipid metabolism in the jejunum, membrane transport in the ileum, xenobiotics biodegradation in the cecum, and environmental adaptation in the rumen. DISCUSSION: These findings provide a genome-resolved view of CF repertoire organization in cervid gut microbiomes and demonstrate that colonization-associated functions are structured across microbial lineages and ecological contexts. This study highlights the importance of considering microbial taxonomy and host-associated environments when interpreting the distribution of CF repertoires in mammalian gut ecosystems.

Cervidae↗
PubMed2025

Mapping the oral microbiome opens links to periodontitis.

Many microbiome analysis techniques can only detect the microbes present in the reference genome database used. In this issue of Cell Host & Microbe, Cha et al. establish an improved genome database of the human oral microbiome, which they use to discover a connection between periodontitis and an enigmatic bacterial phylum.

Humans↗
PubMed2026

Adaptive Evolution Reveals Metabolic Plasticity and Functional Redundancy in an Anaerobic Microbiome under Extreme Ammonia Stress.

Ammonia toxicity represents a primary biochemical bottleneck governing microbial community structure and performance during the anaerobic digestion of the organic fraction of municipal solid waste. However, the mechanistic basis of microbial adaptation to chronic ammonia levels remains poorly characterized. In this study, a long-term sequential enrichment strategy under progressively increasing ammonia concentrations (350-1500 mgN L-1), integrated with genome-centric metagenomics and metatranscriptomics, was employed to resolve the response of an organic waste-degrading microbiome over a 240 day period. Increasing ammonia pressure induced a progressive decline in methanogenesis and accumulation of volatile fatty acids, particularly acetate. Despite these inhibitory pressures, methane production was only halved relative to the initial baseline reflecting a resilient methanogenic community. This stability was driven by a restructuring of the microbiome, where functional redundancy across divergent taxa preserved core metabolic functions. Key adaptive responses included the reconfiguration of carbon fixation pathways, specifically via a variant of the Wood-Ljungdahl pathway coupled with the glycine cleavage system acting as an alternative acetate oxidation route, as well as sustained osmoprotectant biosynthesis. Cellular homeostasis was preserved through H+ replenishment via multiple energy-converting complexes and K+ influx to maintain cation-proton balance. Collectively, these findings demonstrate that metabolic plasticity and the preservation of core metabolic functions are the primary determinants of ammonia resilience, sustaining methane production under inhibitory conditions.

Ammonia↗
PubMed2024

Predictions of rhizosphere microbiome dynamics with a genome-informed and trait-based energy budget model.

Soil microbiomes are highly diverse, and to improve their representation in biogeochemical models, microbial genome data can be leveraged to infer key functional traits. By integrating genome-inferred traits into a theory-based hierarchical framework, emergent behaviour arising from interactions of individual traits can be predicted. Here we combine theory-driven predictions of substrate uptake kinetics with a genome-informed trait-based dynamic energy budget model to predict emergent life-history traits and trade-offs in soil bacteria. When applied to a plant microbiome system, the model accurately predicted distinct substrate-acquisition strategies that aligned with observations, uncovering resource-dependent trade-offs between microbial growth rate and efficiency. For instance, inherently slower-growing microorganisms, favoured by organic acid exudation at later plant growth stages, exhibited enhanced carbon use efficiency (yield) without sacrificing growth rate (power). This insight has implications for retaining plant root-derived carbon in soils and highlights the power of data-driven, trait-based approaches for improving microbial representation in biogeochemical models.

Rhizosphere↗
PubMed2006

Metagenomic analysis of the human distal gut microbiome.

The human intestinal microbiota is composed of 10(13) to 10(14) microorganisms whose collective genome ("microbiome") contains at least 100 times as many genes as our own genome. We analyzed approximately 78 million base pairs of unique DNA sequence and 2062 polymerase chain reaction-amplified 16S ribosomal DNA sequences obtained from the fecal DNAs of two healthy adults. Using metabolic function analyses of identified genes, we compared our human genome with the average content of previously sequenced microbial genomes. Our microbiome has significantly enriched metabolism of glycans, amino acids, and xenobiotics; methanogenesis; and 2-methyl-d-erythritol 4-phosphate pathway-mediated biosynthesis of vitamins and isoprenoids. Thus, humans are superorganisms whose metabolism represents an amalgamation of microbial and human attributes.

Adult↗
PubMed2026

Metabolome-driven rhizosphere microbiome assembly determining the health of medicinal herb (Angelica sinensis) against root rot.

BACKGROUND: The rhizosphere-associated microbiota plays a crucial role in plant responses to disease stress. Plant secondary metabolites are recognized as crucial mediators in the assembly of rhizosphere microbial communities, particularly by enhancing the colonization of beneficial microorganisms. Despite this recognized importance, a deeper understanding of how such metabolome-driven microbiome assembly specifically determines plant resistance against soil-borne diseases is still lacking. RESULTS: Here, we focused on the widely planted medicinal plant Angelica sinensis and demonstrated that root rot-diseased rhizosphere soils (DRS) exhibited a higher relative abundance of Fusarium and a lower relative abundance of Streptomyces compared to healthy rhizosphere soils (HRS). Shotgun metagenomic sequencing revealed that metabolism-associated genes, particularly those related to steroid degradation, are significantly enriched in HRS samples. Subsequent genome and functional gene analysis of Streptomyces revealed that the steroid degradation-related genes are associated with rhizosphere colonization in hosts. Rhizosphere Streptomyces S15 directly antagonized Fusarium and enhanced the root resistance of A. sinensis. Comparative metabolomics showed that A. sinensis plants from HRS secreted more lipid and lipid-like molecules than those from DRS, especially sterol lipids and long-chain fatty acids, which promoted the growth of Streptomyces S15 isolates. Transcriptome analysis validated that the lipid hormones are essential for sporulation, biofilm formation, and streptomycin biosynthesis of S15 strain. Finally, exogenous application of synbiotics (lipid prebiotics and S15) to A. sinensis resulted in the enrichment of S15-homologous Streptomyces amplicon sequence variant (ASV), further establishing beneficial bacterial communities in Fusarium-stressed rhizospheres. CONCLUSIONS: Our study proposes that A. sinensis recruits steroid-metabolizing Streptomyces species by exuding key lipid compounds (i.e., methyl jasmonate and brassinolide) to combat Fusarium root rot. This study provides novel insights into using functional synbiotics as a promising strategy for manipulating plant-microbiome interactions to promote sustainable agriculture. Video Abstract.

Rhizosphere↗
PubMed2024

Shotgun metagenomic analysis of saliva microbiome suggests Mogibacterium as a factor associated with chronic bacterial osteomyelitis.

Osteomyelitis of the jaw is a severe inflammatory disorder that affects bones, and it is categorized into two main types: chronic bacterial and nonbacterial osteomyelitis. Although previous studies have investigated the association between these diseases and the oral microbiome, the specific taxa associated with each disease remain unknown. In this study, we conducted shotgun metagenome sequencing (&#x2265;10 Gb from &#x2265;66,395,670 reads per sample) of bulk DNA extracted from saliva obtained from patients with chronic bacterial osteomyelitis (N = 5) and chronic nonbacterial osteomyelitis (N = 10). We then compared the taxonomic composition of the metagenome in terms of both taxonomic and sequence abundances with that of healthy controls (N = 5). Taxonomic profiling revealed a statistically significant increase in both the taxonomic and sequence abundance of Mogibacterium in cases of chronic bacterial osteomyelitis; however, such enrichment was not observed in chronic nonbacterial osteomyelitis. We also compared a previously reported core saliva microbiome (59 genera) with our data and found that out of the 74 genera detected in this study, 47 (including Mogibacterium) were not included in the previous meta-analysis. Additionally, we analyzed a core-genome tree of Mogibacterium from chronic bacterial osteomyelitis and healthy control samples along with a reference complete genome and found that Mogibacterium from both groups was indistinguishable at the core-genome and pan-genome levels. Although limited by the small sample size, our study provides novel evidence of a significant increase in Mogibacterium abundance in the chronic bacterial osteomyelitis group. Moreover, our study presents a comparative analysis of the taxonomic and sequence abundances of all genera detected using deep salivary shotgun metagenome data. The distinct enrichment of Mogibacterium suggests its potential as a marker to distinguish between patients with chronic nonbacterial osteomyelitis and chronic bacterial osteomyelitis, particularly at the early stages when differences are unclear.

Humans↗
PubMed2025

Metabolism and gene expression models for the microbiome reveal how diet and metabolic dysbiosis impact disease.

The gut microbiome plays a critical role in human health, spurring extensive research using multi-omic technologies. Although these tools offer valuable insights, they often fall short in capturing the complexity of microbial interactions that associate with disease onset, progression, and treatment. Thus, integration of multi-omics datasets with metabolic models is needed to predict associations between microbial activity and disease. Here, we automated the reconstruction of 495 metabolic and gene expression models (ME-models), overcoming the main limitation preventing the wide use of this approach. We integrated them with multi-omics data from patients with inflammatory bowel disease (IBD), identifying taxa associated with variations in amino acids, short-chain fatty acids, and pH in the gut of IBD patients. In general, this approach provides testable hypotheses of the metabolic activity of the gut microbiota, and the automated pipeline opens the opportunity to study microbial interactions in other biologically relevant settings using ME-models.

Humans↗
PubMed2026

From bacterial to microbiome-derived vesicles: genome-informed identity, source qualification, and translational quality for skin-directed cosmetics.

Bacterial extracellular vesicles (BEVs) are increasingly proposed as materials for skin-directed cosmetics, yet rapid adoption of "exosome" terminology has outpaced clarity on their origin, composition, and manufacturing quality. This review argues that the value of BEVs depends on scientific discipline rather than marketing appeal, and that they are promising because they are biologically potent, not because they are intrinsically benign. We retain BEVs as the scientific umbrella term for vesicles released by bacteria and we propose the term microbiome-derived vesicles (MDVs) as the consumer-facing designation for qualified commensal BEVs - a surface term that avoids the difficulty of "bacterial" while its definition preserves bacterial provenance. We develop a three-axis framework for BEV identity that integrates compositional analysis, producer-strain genomics, and functional or safety profiling, and we position whole-genome sequencing (WGS) as decisive for source qualification and mechanistic interpretation but insufficient to prove the efficacy of a purified preparation. Building on this framework, we summarize isolation, purification, and analytical characterization requirements; interpret current skin-efficacy evidence in light of its methodological limits; and discuss formulation, cosmetic application, regulatory positioning, and manufacturable quality. We conclude that transparent bacterial provenance, reproducible preparation, and evidence proportionate to the claims made are prerequisites for evaluating commensal BEVs, described for skin applications as MDVs, as a scientifically defined cosmetic platform.

Bacterial extracellular vesicles↗
PubMed2026

Transcriptomic changes in the gut mucosa of fasting northern elephant seal pups reveal immune modulation during early microbiome establishment.

Fasting is an integral component of the life-history of many species. Following abrupt weaning, northern elephant seal pups (Mirounga angustirostris) undergo an extended post-weaning fast of approximately 60&#xa0;days. During this period, enteric bacterial diversity increases, suggesting that host immune regulation may facilitate the establishment of microbial communities. However, the molecular processes occurring within the intestinal mucosa during this transition remain poorly understood. To investigate these mechanisms, we characterized transcriptional changes in the enteric mucosa of male and female northern elephant seal pups sampled at weaning and after one month of fasting. Total RNA isolated from rectal swabs was sequenced and aligned to the Mirounga angustirostris reference genome. Differential gene expression and gene set enrichment analyses were used to identify genes and pathways associated with fasting and sex-specific responses. Fasting was accompanied primarily by transcriptional downregulation, including genes involved in antimicrobial defense, inflammation, protein turnover, and epithelial remodeling. In contrast, several genes associated with B-cell activity and immune recognition were upregulated. Gene Set Enrichment Analysis revealed coordinated activation of immune-regulatory pathways indicating dynamic modulation of intestinal immunity rather than generalized immune suppression. Pronounced sex-specific differences were also observed. Male pups exhibited transcriptional patterns consistent with enhanced immune tolerance, whereas females showed broader immune-pathway activation, including enrichment of pro-inflammatory and stress-response pathways. Several non-coding RNAs also displayed sex-specific changes in expression. Together, these findings suggest that fasting induces transcriptional remodeling of the gut and may contribute to immune regulation during a critical period of microbiome establishment in northern elephant seal pups.

Animals↗
PubMed2026

Identification and Classification of Expressed Orphan Genes, Spurious Orphan Genes, and Conserved Genes in the Human Gut Microbiome.

Orphan genes (OGs)-genes lacking detectable homologs outside a species-are widespread in microbial genomes and are thought to contribute to their adaptation and molecular innovation. However, not all predicted OGs may represent novel functional coding sequences. False positive OGs, also called spurious OGs, can arise from gene prediction errors. We reason that OGs lacking detectable expression are more likely to be spurious. To test this, we combined large-scale metatranscriptomic profiling of the human gut microbiome with machine learning to distinguish expressed OGs from spurious ones and compare them with conserved genes (CGs) found in multiple species. Using nearly 5,000 metatranscriptome libraries, we identified &#x223c;218,000 OGs supported by expression evidence, while &#x223c;330,000 predicted OGs lacked detectable expression and were classified as spurious. We extracted 154 features for sequence, structural, and evolutionary properties for each gene and trained XGBoost classifiers while accounting for genomic representation. The models achieved an area under the receiver operating characteristic curve (AUC) of 0.82 in distinguishing expressed OGs from spurious OGs and an AUC of 0.93 in distinguishing expressed OGs from CGs. Interpretation based on SHAP (SHapley Additive exPlanations) revealed clear biological signals. Particularly, expressed orphans were present in more genomes than spurious ones, and expressed OGs were shorter than CGs. This work improves OG discovery and suggests that expressed OGs differ systematically from CGs and spurious OGs in sequence composition, structural constraints, and evolutionary signals.

Humans↗
PubMed2025

Altered ruminal microbiome tryptophan metabolism and their derived 3-indoleacetic acid inhibit ruminal inflammation in subacute ruminal acidosis goats.

BACKGROUND: Subacute ruminal acidosis (SARA) is a digestive disorder that often severely jeopardizes the health and lactation performance of ruminants fed a high-energy diet. Different dairy ruminants exhibit varying degrees of inflammation accompanied by variations in the rumen microbiota when SARA occurs. Our understanding of the occurrence of SARA and varying degrees of rumen epithelial inflammation is lacking. Hence, we performed rumen metagenomic, metagenome-assembled genome and metabolomic analyses, with transcriptome and single-nucleus RNA sequence analyses, to explore the microbial mechanism of SARA occurrence and different degrees of inflammation. RESULTS: A total of 36 goats fed two diets with gradually increasing levels of rumen-degradable starch (RDS) were included in this study, and SARA goats fed 70% concentrate diets supplemented with whole corn (HGW-SARA) and SARA goats fed 70% concentrate diets supplemented with crushed corn (HGC-SARA) were identified. Moreover, 11 goats fed a control basal diet, named LGW-CON, were also included. Compared with those in the LGW-CON group, the rumen fermentation capacity was enhanced, accompanied by ruminal epithelial and systemic inflammation, in goats from HGW-SARA and HGC-SARA. Between them, HGC-SARA goats presented less inflammation. Notably, the ruminal inflammation-related pathways were increased only in the HGW-SARA group but not in the HGC-SARA group. Metagenomic analysis revealed that the &#x3b2; diversity of SARA goats was significantly different from that of LGW-CON goats. Ruminococcus significantly increased in both SARA groups, whereas Prevotella and Bacteroidales significantly decreased, which was accompanied by a decrease in cellulose and hemicellulose enzymes and an increase in lysozymes and lipopolysaccharide synthesis enzymes. Multi-omics analysis of the ruminal contents and tissues suggested that epithelial inflammation was caused by disturbed ruminal microbiome-induced Th17 cell differentiation and IL-17 signalling pathway activation. Comparative analyses between the HGW-SARA and HGC-SARA groups highlighted the importance of Selenomonas and Bifidobacterium, as well as bacterial tryptophan metabolism, in the production of 3-indoleacetic acid, which mitigated ruminal epithelial inflammation by modulating Th17 cells and inhibiting IL-17 signalling. Ruminal microbiota transplantation from HGW-SARA goats to healthy dairy goats and mice revealed the role of microbes in epithelial inflammation. Additionally, 3-indoleacetic acid supplementation reduced rumen inflammation and the IL-17 concentration in the serum, improved VFAs absorption, and enhanced milk production. CONCLUSIONS: This study unveiled that after SARA was induced by high-concentrate feeding, the rumen homeostasis was disrupted, and rumen fiber degradation capacity of dairy goats decreased, but the LPS synthesis capacity increased, and inflammation of the rumen epithelium was observed. However, the ruminal microbial species from the Bifidobacterium and Selenomonas genera and bacterial 3-indole acetic acid are pivotal in mitigating ruminal epithelial inflammation during SARA in dairy goats. This could potentially be attributed to the modulation of ruminal Th17 cell proportions and the inhibition of IL-17 signalling pathways. Video Abstract.

Rumen↗