Microbiome最新文献

Background: Intestinal aging manifests as the decline in gut function and structure, affecting nutrient absorption and overall health. Agarose oligosaccharides (AOS) exhibit considerable anti-aging effects, but their mechanism of action remains unclear.

Results: Here, aging male Drosophila melanogaster (D. melanogaster) were employed to evaluate the effects of AOS on the proliferation and differentiation of intestinal stem cell (ISC) and its underlying mechanism. Our findings revealed that supplementation with AOS significantly extended mean and maximum lifespan, reduced oxidative stress, and alleviated intestinal epithelial barrier dysfunction. Notably, AOS supplementation reduced the mean fluorescence intensity of esg⁺ cells and enteroblasts (EB), leading to an improvement in ISC homeostasis, with potential mechanisms associated with activation of the PERK and JAK/STAT signaling pathways, as demonstrated by RNA interference. Integrated 16S rRNA sequencing, strain isolation, and short-chain fatty acids (SCFAs) analysis revealed that AOS was beneficial for intestinal microflora and its metabolites, evidenced by the significant increase in Acetobacter persici and acetic acid contents. Importantly, further experiments demonstrated that Acetobacter persici and acetic acid treatment could significantly decrease the esg⁺ ISC count and downregulate the expression levels of PERK, STAT, and Hsp70Bbb, suggesting that AOS can increase production of Acetobacter persici and its metabolite acetic acid, thereby modulating JAK/STAT signaling to improve ISC steady-state.

Conclusions: The homeostasis of ISC in aging D. melanogaster is balanced by AOS via the acetic acid-JAK/STAT axis mediated by Acetobacter persici. This axis counters age-related ISC dysregulation by balancing proliferative signals with redox homeostasis, positioning AOS as a microbiota-targeted intervention for age-associated intestinal decline.

Motivation: Recent research has revealed strong correlations between the human microbiome and various diseases. However, statistical analysis of microbiome data remains challenging due to its inherent sparsity and high dimensionality. PERMANOVA (Permutational multivariate analysis of variance using distance matrices) has been extensively employed to test the association between microbiome data and biological features. Its non-parametric nature makes it appealing, as it does not impose restrictions on data dimension or distribution. Despite its merits, several limitations have restricted its further application.

Results: This paper introduces E-MANOVA (Ensemble multivariate analysis of variance using distance matrices), a method designed to address these limitations. Traditional PERMANOVA lacks consistent robustness across different distance metrics and association signals, which can lead to power reduction in specific scenarios. Leveraging the idea of ensemble learning, we construct base tests by taking the similarity matrix to the rth power and then combine these tests to build a final ensemble test. Our resulting test statistic exhibits high power and robustness compared to other existing methods. Furthermore, we employ direct moment approximation and the Pearson type III distribution to approximate the permutation null distribution, completely avoiding the computationally intensive permutation procedure. Finally, we utilize the Cauchy combination method to aggregate p-values from multiple distances, eliminating the need to pre-specify a single distance measure before analysis.

Conclusions: Our extensive simulations demonstrate that the proposed method outperforms existing methods across various situations. Further analysis of real data from cigarette smokers and curated microbiome data shows that our proposed method identifies the highest number of significant associations among all competing methods. Video Abstract.

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 + 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 + 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 < 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.

Background: Crop wild relatives and their microbiomes are essential for sustainable crop production. However, the co-evolution of wild rice species and their microbiomes remains poorly understood. Herein, we investigated microbiome assembly across 17 wild rice and one cultivated rice species under controlled conditions spanning ~15 million years of evolution.

Results: Our data reveal distinct eco-evolutionary patterns for bacteria and fungi. Host divergence time was the predominant driver of root microbiota structure, outweighing polyploidy and life cycle, and exerted a stronger effect on bacteria than fungi. Bacterial community exhibited a significant phylosymbiosis with its host, but fungi did not. Over evolutionary time, bacterial diversity decreased while phylogenetic clustering increased. Deterministic and stochastic processes co-drove bacteria assembly, whereas stochastic processes strongly drove fungi assembly. Potentially functional taxa, including nitrogen-fixing and methane-cycle bacteria, were differentially enriched across evolutionary time and polyploidization events. Notably, co-speciating bacteria better predicted grain weight than fungi, with core species making a major contribution. Using a synthetic community (SynCom) derived from the wild rice core microbiome and four nitrogen-fixing strains enriched in early- and medium-diverging Oryza species, we demonstrated that the SynCom strongly promoted rice growth, with the removal of key members markedly reducing its impact.

Conclusions: These results reveal co-phylogenetic patterns between Oryza and root-associated bacteria, highlighting the closer functional linkage between rice traits and bacteria than fungi, likely due to their co-evolution. Our findings provide new insights into crop-microbiome symbiosis from an eco-evolutionary perspective and underscore the importance of co-speciating microbiomes from wild relatives in supporting crop growth. Video Abstract.

Background: Early-life lincomycin and related antibiotics exposure affected gut microbiota composition and intestinal health, but which microbes play a dominant role in this process remains unclear.

Results: Lactobacillus reuteri was suppressed in piglets exposed to lincomycin. Meanwhile, early-life lincomycin exposure caused intestinal morphological damage and decreased the expression of Claudin-1, Occludin, and ZO-1. Mice transplanted with lincomycin-exposed piglet fecal microbiota showed more severe inflammation and weight loss after LPS infection, and decreased colon Lactobacillus abundance. Furthermore, mice supplemented with Lactobacillus reuteri SKLAN202402ZF showed reduced lincomycin-related intestinal damage and inflammation after LPS infection. Specifically, Lactobacillus reuteri SKLAN202402ZF inhibits the expression of TLR4, MyD88, and NLRP3, and thus reduced the release of inflammatory factors such as IL-1β, IL-18, IL-17.

Conclusions: Lincomycin exposure affects the composition of gut microbes and increases subsequent susceptibility to LPS, while Lactobacillus reuteri SKLAN202402ZF has protective potential against antibiotic- associated intestinal inflammation.

Background: Host-microbiome interactions play essential roles in the development of Alzheimer's disease (AD), yet the host genetic impacts on gut microbial alterations in AD remain poorly understood.

Results: Here, we simultaneously profiled host genotype and gut microbiome in 252 Chinese individuals with varying degrees of cognitive disability. Using the latent Dirichlet allocation topic model, we identified the Anaerostipes-enriched enterosignature (ES-Ana) at the microbial subgroup level as significantly negatively associated with cognitive disability, which could be recapitulated in external cohorts. With the whole-genome sequencing data, we performed microbiome genome-wide association studies for the ES-Ana relative abundance. We prioritized 41 lead genetic variants and confirmed that the high ES-Ana relative abundance showed a negative correlation with the polygenic risk score of AD, indicating its protective effect against AD. Furthermore, we identified 174 ES-Ana-associated genes, which are enriched in AD-related biological functions and phenotypes, and exhibite pervasive underexpression in glial cells during brain aging.

Conclusions: In summary, our study reveals the complex genetic effects on the gut microbiota in AD, and provides novel evidence for the roles of the gut-brain axis in AD. Video Abstract.

Background: The vaginal and penile coronal sulcus microbiome influence reproductive health outcomes and susceptibility to multiple sexually transmitted infections including HIV. There is evidence that genital bacteria are shared between heterosexual partners during sex, but the dynamics of this microbiota exchange remain poorly understood.

Results: Using microbiome characterization from established heterosexual couples, we found that condomless penile-vaginal sex dramatically altered the coronal sulcus microbiome, with transient dominance by Lactobacillus spp. Conversely, condom-protected penile-vaginal sex did not result in significant shifts in overall composition (p = 0.63). Significant changes were observed in the female partner's genital microbiome, including increased Corynebacterium spp. and increased abundance of Bacteria Associated with Seroconversion, Inflammation, and Cells (BASICs) (Prevotella bivia, Peptostreptococcus anaerobius, Dialister micraerophilus, Prevotella disiens, Dialister propionicifaciens, Dialister succinatiphilus) in individuals with a colonized male partner. By 72 h post-coitus L. iners cell-normalized abundance remained elevated in the penile microbiome, but other taxa returned to baseline levels. Causal mediation analysis indicated a pH-mediated increase in vaginal Gardnerella at 72 h.

Conclusions: Condom-protected penile-vaginal sex was associated with minimal genital microbiome changes, whereas condomless penile-vaginal sex among established couples led to extensive exchange of genital microbiota. Most disruptions to the microbiome resolved within 2-3 days, although changes in vaginal pH were associated with longer-lasting increases in Gardnerella abundance. Video Abstract.

Background: Stress experienced by newly received cattle is a significant challenge in the beef industry, frequently resulting in weakened immune responses and impaired growth. The rumen microbiota is essential to host health, and its imbalance can exacerbate stress. This study investigates the mechanisms by which creatine pyruvate (CrPyr) mitigates stress in newly received cattle through multi-omics approaches, including metagenomics, metabolomics, in vitro and in vivo experiments, and rumen microbiota transplantation (RMT) in mice.

Results: Our results revealed that CrPyr significantly reduces stress-related hormones (cortisol and adrenocorticotropic hormone) and inflammatory markers (IL-6, IL-1β, and TNF-α), and enhanced antioxidant capacity (SOD: 57.38 versus 46.93 U/mL, P < 0.05; GSH-Px: 305.87 versus 217.07 U/mL, P < 0.05; T-AOC: 9.62 versus 7.66 U/mL, P < 0.05). Metagenomic analysis demonstrated that CrPyr increased Prevotella abundance, a key rumen bacterium involved in volatile fatty acid (VFA) production, and enriches metabolic pathways associated with energy metabolism (ATP synthesis, and pyruvate metabolism) and antioxidant defense (glutathione metabolism, FC = 1.08, P < 0.05). In vitro and in vivo experiments, as well as RMT studies in mice, further validate these findings, demonstrating that CrPyr promote VFA synthesis and increased ATP production through the electron transport phosphorylation pathway.

Conclusions: CrPyr modulates the abundance of ruminal Prevotella in transport-stressed cattle to enhance glutathione and VFA metabolism and to accelerate ATP and nucleotide synthesis, thereby alleviating stress in newly received cattle. This multimodal approach established CrPyr as an effective nutritional intervention that improves rumen function and increases livestock productivity. Video Abstract.

Background: Probiotics have been widely used for the regulation of intestinal health. Current screening methods for probiotics typically rely on animal or two-dimensional cell models. In this study, we employed intestinal organoids to identify a candidate probiotic strain. Furthermore, we investigated the potential mechanisms through which this strain and its active metabolites exert their effects, thereby evaluating the efficacy of this screening approach.

Results: Firstly, candidate probiotic strain PGM541 was identified from a porcine-derived Bacillus library by assessing organoid viability. Subsequently, to validate the organoid screening reliability, the potential mechanism of strain PGM541 on the intestinal epithelium was investigated; it was found to exhibit probiotic functions by regulating cell proliferation in both in vitro organoid and in vivo piglet models. Furthermore, organoid screening combined with metabolomic analysis identified butyric acid (BA) as the key bioactive metabolite responsible for driving epithelial proliferation. Whole-genome and transcriptomic analyses revealed the biosynthetic pathway of BA in strain PGM541. Importantly, BA receptor blockade experiments directly confirmed that BA enhances epithelial proliferation via interaction with the FFAR2 receptor, thereby validating its functional activity. Additionally, strain PGM541 exhibited protective effects against dextran sulfate sodium (DSS)-induced colitis, further validating the effectiveness of the intestinal organoid platform for probiotic screening.

Conclusions: The probiotic strain PGM541, which was screened using intestinal organoids, promotes intestinal epithelial cell proliferation via its metabolite BA activating the FFAR2 receptor. These findings demonstrate that the intestinal organoid model serves as an effective platform for both preliminary probiotic screening and mechanistic investigation. Video Abstract.

Background: The gut microbiota influences poultry health, nutrition, feed efficiency (FE), and overall productivity. However, the relationship between gut microbes, including bacteria and phages, and FE in ducks remains underexplored. To address this, we integrated cecal 16S amplicon, metagenome, microbiota-derived short-chain fatty acids (SCFAs) profiling, liver transcriptome, and serum metabolome data to illustrate the contribution of the gut microbiome (bacteria and viruses) to duck FE.

Results: We reconstructed viral genomes and prokaryotic metagenome-assembled genomes (MAGs) and annotated their genes using comprehensive databases. Prokaryotic hosts of viruses were also predicted to understand virus-host dynamics within the gut ecosystem. Our results revealed that high-FE ducks have higher concentration of propionate and butyrate in cecum compared with low-FE ducks. The metagenome sequencing revealed distinct cecal microbiota profiles between two groups, with increased relative abundance of representative SCFA producers, especially Paraprevotella sp905215575 and Bacteroides sp944322345, and enhanced SCFA-biosynthesis pathways in high-FE ducks. Virome genome assembly identified two phages encoding auxiliary metabolic genes (AMGs) involved in pyruvate metabolism, enhancing nutrient availability for host bacteria to produce SCFAs (e.g., temperate phage-encoded pyruvate phosphate dikinase) or exploiting host central metabolic pathways for viral replication (e.g., lytic phage-encoded formate C-acetyltransferase). Furthermore, these representative SCFA-producing bacteria and phage consortia were associated with serum metabolites (including L-histidine and 4-hydroxydecanedioylcarnitine) linked to duck FE.

Conclusion: Collectively, these findings provide novel insights into the gut microbial factors regulating FE in ducks, offering potential strategies to optimize poultry nutrition and productivity. Video Abstract.