Microbiome最新文献

Background: Gut microbiota dysbiosis has been implicated in the pathogenesis of depression. Our previous studies identified loganin as a potential antidepressant agent; however, its oral bioavailability is low. Whether loganin alleviates depression via modulation of the gut microbiota remains unclear.

Methods: Chronic unpredictable stress mice model was used to evaluate the antidepressant-like effects of loganin. To determine the role of gut microbiota, mice were treated with an antibiotic cocktail (ABX) to deplete microbiota. Fecal microbiota transplantation (FMT) from loganin-treated donors and Muribaculum intestinale (M. intestinale) were performed to assess microbial contributions.

Results: Loganin exerted antidepressant-like effects by modulating gut microbiota, as evidenced by reduced efficacy in ABX-treated mice and behavioral improvements in recipients of FMT from loganin-treated donors. Loganin modulated gut microbiota composition particularly increasing the abundance of Muribaculum, and increased short-chain fatty acids (SCFAs). M. intestinale alleviated depressive-like behaviors, prompted the butyrylation of RORγt, inhibited Th17 cells differentiation, and suppressed M1 microglia polarization. Importantly, overexpression of RORγt attenuated the behavioral benefits of M. intestinale.

Conclusion: Loganin exerts antidepressant-like effects by enriching Muribaculum and SCFAs, thereby inhibiting Th17 cell differentiation and M1 microglia polarization. M. intestinale may represent a promising microbial-based therapeutic strategy for depression.

Background: The majority of bacteria in the vertebrate gut harbor integrated bacterial viruses ("bacteriophages" or "phages"; integrated phage are termed "prophages"). To probe phage replication strategies in the mammalian gut microbiome, we investigated phage activity in a large longitudinal study of diversity outbred mice (913 animals) undergoing extreme dietary restriction with detailed phenotypic characterization across lifespan.

Results: We assembled 54,119 candidate DNA viral genomes from 2997 longitudinal metagenomes, forming 6462 viral operational taxonomic units (vOTUs). Over 85% of vOTUs annotated as novel. Viruses annotated predominantly as prophages in the Caudoviricetes class. We detected no eukaryotic DNA viruses, and none of the strictly lytic Crassvirales order that is abundant in human gut. The most prevalent phages had the widest predicted host ranges. The relative abundance of most phages was highly correlated to that of their inferred host bacteria, suggesting quiescent prophages dominate viral metagenomes, consistent with "piggyback-the-winner" dynamics. After accounting for close phage-bacterial covariation, we did identify a subset of phages changing in relative abundance and prevalence relative to their hosts in response to dietary restriction and aging. In particular, phages with larger genomes become less common in diets with restricted calories, potentially reflecting a higher fitness cost to their host. Generalist phages were enriched for a gene encoding a single-strand DNA binding protein which is reportedly involved in DNA repair and protection from nucleases encoded by host cells. Lytic phages became more common with aging, and we observed a reduction in phage richness with age, both findings previously observed in human cohorts.

Conclusion: These studies enrich our understanding of DNA phage dynamics in gut while emphasizing the predominance of "piggyback-the-winner" strategies.

Background: T cells cooperate with the intestinal microbiota to coordinate antimicrobial defense, but whether this crosstalk arose as an independent innovation in mammals or represents an evolutionarily conserved feature of vertebrate immunity remains unknown.

Results: Using the teleost Nile tilapia as a model, we demonstrate that both systemic and localized infection with Edwardsiella piscicida induce enteritis, correlated with robust intestinal T cell responses. Selective T cell depletion triggered excessive expression of proinflammatory cytokines, impaired mucosal architecture, and diminished host resistance to infection, underscoring the essential role of T cells in gut immunity. Strikingly, T cell depletion also caused profound alterations in gut microbial composition, characterized by a sharp decline in beneficial taxa such as Cetobacterium and the expansion of opportunistic pathogens including Klebsiella and Acinetobacter, indicating that T cells are required to maintain microbiome homeostasis. Conversely, broad-spectrum antibiotic eradication of the microbiota provoked hyperproliferation of intestinal T cells and barrier disruption, revealing reciprocal regulation between T cells and commensals. From the gut content, we isolated a C. somerae strain SH518, whose dietary supplementation for 6-8 weeks enhanced the activation, proliferation, and effector function of intestinal T cells, preserved mucosal homeostasis during E. piscicida challenge, and even boosted systemic T cell immunity in the spleen.

Conclusions: Collectively, these findings demonstrate that teleost T cells engage in bidirectional interactions with gut microbiota to orchestrate both antimicrobial defense and mucosal homeostasis. We therefore propose that T cell-microbiota cooperation represents an evolutionarily ancient strategy predates terrestrial adaptation, offering new insights into the coevolution of mucosal T cell immunity and microbiome. Video Abstract.

Background: Metabolic syndrome disrupts metabolic resilience in periparturient sows and compromises piglet growth. As intestinal microbes govern host energy homeostasis, microbiome-directed feed additives represent a practical solution. We therefore evaluated the Tibetan‑pig isolate Bacillus amyloliquefaciens TL106, previously validated in weanlings for its capacity to alleviate sow-associated metabolic syndrome.

Results: In a 43‑day trial (20 sows per group), dietary TL106 (5 × 10⁹ CFU kg^-1) increased digestibility of crude fiber (+ 12.5%, p < 0.05) and crude fat (+ 9.3%, p < 0.01), lowered serum IL‑1β (- 34%) and TNF‑α (- 28%), and boosted antioxidant enzymes and immunoglobulins (all p < 0.05). Litter performance improved, with a two‑thirds reduction in diarrhea and heavier piglets at 21 days (+ 15%, aggregate n = 300). Multi‑omics profiling revealed higher cecal α‑diversity, enrichment of butyrate‑producing Ruminococcus and Butyricicoccus (log₂C 2.1 and 1.8; FDR < 0.05), and activation of histidine‑metabolism and ABC‑transporter pathways (q ≤ 0.03) in piglets, while pathways for amino‑acid biosynthesis, lipid utilization, and steroidogenesis were favored in sows.

Conclusions: Bacillus amyloliquefaciens TL106 simultaneously enhanced maternal metabolic health and neonatal development by reshaping gut microbiota and host metabolism, positioning it as a micro‑ecological tool for managing metabolic syndrome in Landrace × Yorkshire sows and Duroc × Landrace × Yorkshire suckling piglets. Video Abstract.

Background: Second-generation antipsychotics (SGAs) are increasingly being utilized in children and adolescents. Risperidone, one of the most commonly prescribed SGAs in this population, has been found to adversely affect cognitive function; however, limited knowledge exists regarding the impact of risperidone on the gut microbiome-brain axis. We hypothesized that the cognitive impairment induced by risperidone is mediated by alterations in the gut microbiome and its metabolites.

Results: In this study, we found that early-life risperidone exposure impaired cognition in mice, including deficits in behavior tests and hippocampal dendritic architecture. The risperidone-exposed mice also exhibited gut microbiota dysbiosis along with damage to the intestinal barrier. Fecal microbiota transplantation (FMT) from treated donors to recipients demonstrated the causal role of the gut microbiome in risperidone-induced cognitive deficits. Of note, risperidone increased the abundance of species Escherichia coli, Eggerthella lenta, Ruminococcus gnavus, Clostridium perfringens, Clostridium difficile, and Blautia hydrogenotrophica. These altered species are identified to encode 7α-HSDH, 3β/α-HSDH, TyrB, and porA, the key enzymes in secondary bile acid metabolism and tyrosine metabolism. Furthermore, a significant reduction in tauroursodeoxycholic acid (TUDCA, the metabolite of bile acid metabolism) and accumulation of p-cresol (the metabolite of tyrosine metabolism) were observed in the brains of mice exposed to risperidone. Mechanically, TUDCA prevented cognitive impairment and endoplasmic reticulum (ER) stress in the hippocampus induced by risperidone, while p-cresol induced neuronal ER stress. Knockout of protein tyrosine phosphatase 1B (PTP1B, ER stress-associated protein) in neurons ameliorated cognitive impairment and neurological damage induced by risperidone.

Conclusions: This study, for the first time, reveals that early risperidone exposure induces gut microbiome dysbiosis and disturbs the bile acids/tyrosine-PTP1B axis to impair cognitive function. These findings alert the risk of gut and neurological side effects of SGAs treatment and highlight that it is crucial to maintain gut homeostasis during the brain developmental phases of children and adolescents with SGAs exposure. Video Abstract.

Background: The global decline of coral reefs underscores the urgency of understanding how corals enhance resilience in stressful environmental conditions. As metaorganisms, or holobionts, corals rely on dynamic interactions with their associated microbial communities, with bacterial restructuring proposed as a potential mechanism of holobiont adaptation. Here, we reconstructed coral symbiosis in the bleached tissues of Acropora hyacinthus by introducing beneficial bacteria and thermally domesticated Symbiodiniaceae to assess their roles in bleaching recovery. Raman spectroscopy metabolomics (RS metabolomics) enables in situ detection, providing temporal evidence of metabolic exchange within the tripartite relationship among corals, Symbiodiniaceae, and associated bacteria.

Results: This study highlights the potential of acclimation-based approaches in the development of thermotolerant Symbiodiniaceae strains. Furthermore, by manipulating this bacterial community, we identified a bacterium that enhances the thermal and light tolerances of acclimated Symbiodiniaceae, offering new insights into coral reef homeostasis strategies. Our results also indicate that the introduction of beneficial bacterial strains and thermotolerant Symbiodiniaceae, including proteins, lipids, and carbohydrates, increased nutrient levels in the coral host.

Conclusions: This work introduces a microbial-assisted holobiont reconstitution framework that advances understanding of cross-kingdom metabolic integration and offers a mechanistic basis for engineering coral resilience under climate stress. The findings could provide insights into leveraging beneficial microbiota to mitigate thermal-induced coral bleaching, ultimately informing conservation strategies for marine ecosystems. Video Abstract.

Background: Ecologically derived synthetic communities can provide robust plant benefits, yet generalizable rules for assembling multifunctional consortia remain limited. We hypothesized that a "top-down" community assembled from an ecological core would yield complementary functions and resilience superior to reductionist mixes.

Results: We distilled an eight-member, Bacillus-dominated synthetic community (hereafter referred to as SynCom) from a rice-duckweed agroecosystem by targeting taxa consistently shared across soil, root and shoot niches. Under greenhouse conditions, the SynCom concurrently promoted rice growth and suppressed sheath blight caused by Rhizoctonia solani, reducing the final disease index by 70% without detectable phytotoxicity. Leave-one-member perturbations (-Dx), combined with untargeted LC-MS profiling and qRT-PCR of biosynthetic genes, revealed a division-of-labor architecture: individual strains specialized in auxin production, siderophore-linked iron mobilization, or lipopeptide/polyketide-based antagonism. These complementary yet partially redundant contributions mapped members, metabolite pools, plant outcomes and rendered community performance resilient to single-member loss. Across -Dx contrasts, the complete SynCom uniquely recovered the full suite of plant-growth metabolites (e.g., indole-3-acetic acid, acetoin/2,3-butanediol) together with antimicrobial chemistries (e.g., surfactin, bacillomycin, fengycin, difficidin). We formalize an assembly heuristic, ecological core, complementary functions, redundancy check, that links ecological origin to predictable, multi-trait performance.

Conclusions: A top-down, ecology-guided route can generate a multifunction SynCom with demonstrated greenhouse efficacy and mechanistic transparency. By coupling-member perturbations with multi-omics readouts, our study provides a transferable rule for building resilient plant-associated consortia and a tractable framework for future genetic and in-plant chemical confirmations. Video Abstract.

Background: Marine algae represent major producers of complex polysaccharides and serve as hosts for diverse microbial communities in the phycosphere. Flavobacteriaceae are among the key bacterial taxa involved in polysaccharide degradation and carbon remineralization in this environment. However, the extent to which algal hosts drive the divergence of polysaccharide utilization profiles in these bacteria remains unclear.

Results: We conducted a genome-resolved analysis of 103 cultured Flavobacteriaceae strains isolated from red, green, and brown macroalgae, as well as from diatoms and dinoflagellates. We found that macroalga-associated strains generally harbored more abundant and diverse CAZyme-encoding genes than their microalga-associated counterparts. Moreover, strains associated with different algal phyla showed distinct metabolic specializations that aligned with the typical polysaccharides of their respective hosts, strongly supporting host-specific adaptation. In four widely distributed genera (Maribacter, Flagellimonas, Polaribacter, Winogradskyella), CAZyme profile dissimilarity and key glycoside hydrolase gene divergence exhibited phylogenetic congruence with algal host phylogeny (Mantel r up to 0.76 and 0.85, respectively), indicative of host-associated functional adaptation. Using Maribacter as a model, cultivation experiments and transcriptome characterization demonstrated that polysaccharide utilization efficiency is not solely linked to the organization of genes into polysaccharide utilization loci (PULs), but also associated with the expression dynamics of key transcription factors (TFs), particularly those from AraC and DeoR families, whose expression patterns were coordinated with laminarin degradation. Notably, these two TF families also exhibited host-associated divergence patterns similar to those of CAZyme-encoding genes. Furthermore, analysis of the Tara Oceans metagenomic data indicated that, within the AraC and DeoR families, a higher proportion of genes were positively correlated with chlorophyll a content compared to other TF families, reinforcing their specialized roles in alga-associated bacterial lifestyles.

Conclusions: Our integrative genomic and transcriptomic analyses reveal evolutionary and regulatory adaptation of marine Flavobacteriaceae to distinct algal hosts. These findings highlight algae-derived habitats as specialized niches that shape microbial metabolic potential, and suggest that carbohydrate metabolism plays a key role in host-driven bacterial evolution across global oceans. Video Abstract.

Background: Feces represent a complex biological matrix that provides valuable information about intestinal physiology and gut microbial activity. Comprehensive fecal DNA sequencing is mostly utilized as a non-invasive way to profile the gut microbiome, and both clinical practice and research on inflammatory bowel diseases (IBD) would greatly benefit from accurate and non-invasive methods to monitor gut inflammation in IBD patients. In IBD, excessive immune cell recruitment and epithelial cell shedding in the gut increase the amount of human DNA in feces, making fecal DNA profiling a desirable approach to monitor gut inflammation dynamics.

Methods: We used a combination of sequencing techniques to comprehensively characterize the fecal DNA diversity in a newly established cohort of pediatric IBD patients and controls (Pediatric cohort, N = 134 children, Israel). We performed methylation-based human cell-specific profiling together with shotgun metagenomics to characterize the human and the microbial DNA content in feces, respectively. Moreover, we included a large complementary external cohort including adult IBD patients and controls (Adult cohort, N = 689 adults, the Netherlands), not only to compare microbial patterns across the age spectrum, but also to extend our findings from the methylation-based profiling to the more broadly-available quantification of human DNA in metagenomic sequencing.

Results: We found that neutrophil DNA dominates fecal human DNA content in IBD patients, and our measurements were highly correlated with fecal calprotectin levels. Combining neutrophil and other cell type DNA fractions in one metric was able to distinguish between remissive and active cases of IBD. Human reads percentage by metagenomics was well correlated with disease severity and species richness, which had distinct trends in CD and UC over time. We used a combination of species richness, human DNA percentage, and microbiome composition data to predict IBD and distinguish CD from UC in both adult and pediatric IBD cohorts.

Conclusions: The comprehensive characterization of human and microbiome fecal DNA is a useful approach to track immune response level and investigate the interaction that the immune system has with gut microbiome richness and composition over time, enriching opportunities for better disease monitoring and thus better treatment of IBD patients. Video Abstract.

Background: The Longmen Grottoes archeological site is a representative of the UNESCO World Heritage. Unfortunately, the long-term exposure to the outdoor environment has caused severe damage to the limestone heritage at this archeological site due to microbial colonization and biodeterioration. However, a lack of understanding of the microbiomes and mechanisms involved in biodeterioration processes has largely restricted the development of sustainable conservation of the heritage there.

Results: Here, we systematically compared physicochemical characteristics between the low and high biodeterioration caves, identified the keystone microbial communities and functions that shape the biodeterioration dynamics, and explored the biogeochemical cycles of carbon, nitrogen, and sulfur that drive the biodeterioration divergence. As a result, physicochemical parameters of the bio-deteriorated rocks of the caves suggest a substantial divergence of biodeterioration. Microbial community structures and functions revealed that the metabolic potential of carbon fixation, nitrification, and denitrification processes shape the biodeterioration dynamics. The results strongly suggest that nitrification is a major contributor to the observed biodeterioration divergence.

Conclusions: We revealed that cyanobacteria, as the main organic carbon producer, support the development of microbiomes that drive the biogeochemical cycles of carbon, nitrogen, and sulfur. Importantly, corrosion of minerals by microbial acids through ammonia oxidation and nitrification is the main consequence of the biodeterioration dynamics. Our findings will provide a basis for sustainable conservation of outdoor stone heritage from microbially induced biodeterioration. Video Abstract.