Microbiome最新文献

Background: Gut microbiota has been established as a critical regulator of human longevity, but the mechanistic role of rumen microbiota in dairy cow productive lifespan remains unexplored. This study investigated differences in rumen microbial community structure and metabolic signatures in a longitudinal cohort of dairy cows with divergent productive lifespans, aiming to elucidate the correction and potential regulatory mechanisms governing dairy cow longevity through microbial-host metabolic reprogramming.

Results: Our longitudinal study identified critical trends linked to increasing parity in dairy cows: milk yield and rumen microbiota diversity declined progressively, with microbial communities restructuring to show 37% higher abundance of Alphaproteobacteria and Pseudomonadota in cows with ≥ 4 parities compared to younger cohorts (parities 1-3). A key parity threshold was observed at the 4th lactation: early-parity cows (1-3) maintained energy-efficient metabolism via glycolysis/gluconeogenesis and TCA cycle, while ≥ 4th parity cows exhibited fundamental metabolic shifts-including altered methane-related gene expression, fermentation profile transitions from propionate- to acetate-dominated VFAs, and lipid dysregulation-alongside impaired nutrient conversion efficiency despite active B vitamin biosynthesis. These changes triggered pro-inflammatory metabolite accumulation, leading to systemic inflammation (elevated IL-1β/TNF-α/IL-6 levels) and reduced antioxidant capacity. Murine rumen microbiota transplantation experiments confirmed causality, with recipients of ≥ 4th parity microbiota developing gut barrier dysfunction and hepatic inflammation via TLR4/NF-κB pathway activation.

Conclusion: Longitudinal analyses classify rumen microbial dysbiosis as a potential driver of reduced productive longevity and lactation performance decline in dairy cows, suggesting that the temporal dynamics of the rumen microbiota influence lactation persistence and productive lifespan. This study fills the gap in microbiota-targeted strategies to extend dairy cows' productive longevity through precision microbial consortium modulation. Video Abstract.

Background: Beef, known for its high protein, low fat, and rich amino acid content, is a premium source of nutrition compared to other meats. As living standards improve, higher demands are being placed on beef quality, which is closely related to intramuscular fat (IMF) content. Jiaxian Red Cattle, a local Chinese breed, is renowned for its high meat quality, characterized by reddish muscle color and snow-white fat. However, the molecular mechanisms underlying differences in intramuscular fat deposition and meat quality in this breed remain unclear. This study aims to explore the potential molecular mechanisms of intramuscular fat deposition in beef cattle using multi-omics approaches.

Results: Non-targeted metabolomic analysis of rumen fluid identified α-linolenic acid as a key metabolite promoting fat accumulation. Four genera-Cnuella, Gaetbulibacter, Moheibacter, and Lacibacter-were significantly positively correlated with α-linolenic acid (r > 0.83, p < 0.05), highlighting their roles in shaping a metabolic environment conducive to intramuscular fat deposition. Pathway analysis revealed that in the high intramuscular fat group (group H-IMF), the fatty acid β-oxidation pathway was significantly inhibited, reducing fatty acid oxidation and promoting fat deposition. Additionally, metabolomic data from longissimus dorsi muscle tissue showed significantly lower levels of N,N,N-trimethyllysine, L-carnitine, and betaine in group H-IMF (p < 0.05). These metabolites were negatively correlated with Cnuella, Gaetbulibacter, Moheibacter, and Lacibacter, indicating a complex interplay between these microbiota and the metabolic network regulating intramuscular fat deposition. These metabolites also interacted with proteins like ACSS1, ACSF2, and MPO to modulate fat formation. In vitro experiments confirmed these findings: overexpression of the MPO gene significantly enhanced intramuscular fat accumulation (p < 0.05), while L-carnitine and betaine suppressed MPO expression (p < 0.05).

Conclusions: This study reveals that Moheibacter, Cnuella, Gaetbulibacter, and Lacibacter play central regulatory roles in intramuscular fat deposition in beef cattle via the α-linolenic acid-fatty acid β-oxidation/L-carnitine-MPO axis. These findings highlight the critical role of microbial communities in regulating fat deposition through complex host-microbe interactions, providing insights for future strategies aimed at enhancing beef quality. Video Abstract.

Background: Metabolite production, consumption, and exchange are intimately involved with host health and disease, as well as being key drivers of host-microbiome interactions. Despite the increasing prevalence of datasets that jointly measure microbiome composition and metabolites, computational tools for linking these data to the status of the host remain limited.

Results: To address these limitations, we developed MMETHANE, a purpose-built deep learning model for predicting host status from paired microbial sequencing and metabolomic data. MMETHANE incorporates prior biological knowledge, including phylogenetic and chemical relationships, and is intrinsically interpretable, outputting an English-language set of rules that explains its decisions. Using a compendium of six datasets with paired microbial composition and metabolomics measurements, we showed that MMETHANE always performed at least on par with existing methods, including blackbox machine learning techniques, and outperformed other methods on 80% of the datasets evaluated. We additionally demonstrated through two cases studies analyzing inflammatory bowel disease gut microbiome datasets that MMETHANE uncovers biologically meaningful links between microbes, metabolites, and disease status.

Conclusions: MMETHANE is an open-source software package that brings state-of-the-art interpretable AI technologies to the microbiome field, emphasizing usability with simple written explanations of its decisions and biologically relevant visualizations. This robust and accurate tool enables investigation of the interplay between microbes, metabolites, and the host, which is critical for understanding the mechanisms of host-microbial interactions and ultimately improving the diagnosis and treatment of human diseases impacted by the microbiome. Video Abstract.

Background: Microorganisms play important ecological roles during interactions with plants, with some strains promoting plant performance. However, the molecular basis of bacterial adaptation to the plant environment remains poorly understood. Microbial plant growth promotion is a complex process that likely involves numerous bacterial genes, many of which remain uncharacterized. In this study, we aimed to identify genes tightly associated with the bacterial adaptation to plant hosts by integrating transcriptomic data from bacteria colonizing roots with comparative genomic and metagenomic analyses.

Results: Here, we identified a set of bacterial genes that were significantly upregulated during root colonization and are more abundant in rhizosphere communities than in bulk soils. Many of these genes had not been previously linked to plant-bacteria interactions. Comparative genomic analyses revealed some of these genes as more prevalent in plant-associated Pseudomonas genomes than in genomes from other environments. We argue that these genes may play relevant biological roles in this host, although only a few have been previously associated with plant colonization. Among them, we focused on a gene homologous to yafL, which encodes a cysteine peptidase of the NlpC/P60 family, known for its role in peptidoglycan remodelling. This gene is more abundant in rhizosphere microbiomes than in bulk soils, and it showed induced expression on the root surface, supporting its ecological relevance in root-associated environments. Functional validation using a knockout mutant confirmed its contribution to plant-bacteria interactions by affecting root architecture and plant growth.

Conclusions: This study provides new insights into the genetic basis of bacterial adaptation to the plant root environment. By integrating transcriptomic and comparative genomic analyses, we identified numerous genes upregulated during root colonization that are enriched in plant-associated Pseudomonas genomes. Our findings highlight previously overlooked bacterial functions with potential roles in plant-microbe interactions. The functional validation of a protein of the NlpC/P60 family supports its involvement in plant-bacteria interactions and underscores the importance of uncharacterized genes in shaping beneficial associations in the rhizosphere. Video Abstract.

Background: Stream hyporheic zones represent a unique ecosystem at the interface of stream water and surrounding sediments, characterized by high heterogeneity and accelerated biogeochemical activity. These zones-represented by the top sediment layer in this study-are increasingly impacted by anthropogenic stressors and environmental changes at a global scale, directly altering their microbiomes. Despite their importance, the current body of literature lacks a systematic understanding of active nitrogen and sulfur cycling across stream sediment and surface water microbiomes, particularly across geographic locations and in response to environmental factors.

Results: Based on previously published and unpublished datasets, 363 stream metagenomes were combined to build a comprehensive MAG and gene database from stream sediments and surface water including a full-factorial mesocosm experiment which had been deployed to unravel microbial stress response. Metatranscriptomic data from 23 hyporheic sediment samples collected across North America revealed that microbial activity in sediments was distinct from the activity in surface water, contrasting similarly encoded metabolic potential across the two compartments. The expressed energy metabolism of the hyporheic zone was characterized by increased cycling of sulfur and nitrogen compounds, governed by Nitrospirota and Desulfobacterota lineages. While core metabolic functions like energy conservation were conserved across sediments, temperature and stream order change resulted in differential expression of stress response genes previously observed in mesocosm studies.

Conclusions: The hyporheic zone is a microbial hotspot in stream ecosystems, surpassing the activity of overlaying riverine surface waters. Metabolic activity in the form of sulfur and nitrogen cycling in hyporheic sediments is governed by multiple taxa interacting through metabolic handoffs. Despite the spatial heterogeneity of streams, the hyporheic sediment microbiome encodes and expresses conserved stress responses to anthropogenic stressors, e.g., temperature, in streams of separate continents. The high number of uncharacterized differentially expressed genes as a response to tested stressors is a call-to-action to deepen the study of stream systems. Video Abstract.

Endometriosis affects approximately 10% of women of reproductive age and is characterized by the presence of endometrial-like tissue outside the uterine cavity, leading to chronic pelvic pain, infertility, and a significant reduction in quality of life. Beyond its local manifestations, endometriosis is increasingly recognized as a systemic, immune-mediated condition with multifactorial origins. In this narrative review, we provide an updated and comprehensive overview of the disease, including its pathophysiology, clinical features, and evolving conceptual frameworks. Considering the frequent digestive symptoms observed in affected patients, we summarize key findings from both animal and human studies that investigate alterations in the gut microbiota. We also review the profound immune dysregulation associated with endometriosis and explore its potential bidirectional relationship with the microbiota. Furthermore, we examine recent insights into the endometrial microbiota-an emerging field of interest given its early involvement in the disease process and its strong interconnection with the vaginal microbiome. Lastly, we highlight studies exploring the gynecological microbiota and present an updated discussion of novel therapeutic strategies, including microbiota-targeted approaches that may shape future management of this complex disease. Video Abstract.

Background: Functional redundancy (FR) in the human gut microbiome is crucial for maintaining stability and resilience, exhibiting a hierarchical structure. However, the precise configuration and functional implications of this hierarchy remain elusive and limited by single-metric measurements. We aimed to develop a method that comprehensively characterizes the hierarchical organization of functional redundancy in personalized microbiomes.

Results: We represented functional redundancy as a network and developed a structural entropy (SE)-based approach to elucidate FR hierarchy, revealing functional redundancy clusters (FRCs)-groups of species capable of independently executing specific metabolic pathways. Through controlled simulations and cross-cohort analyses spanning 4912 gut metagenomes across 28 disease cohorts, we established that our approach offers higher resolution, more comprehensive measurement, and greater robustness in detecting disease-associated functional patterns than traditional FR methods. In healthy individuals, we observed FR network polycentric structure, which shifted to monocentric structure in non-alcoholic steatohepatitis patients. Vitamin biosynthesis FRCs correlated with microbiota transplantation efficiency, while FRCs specialized in short-chain fatty acid production predicted immunotherapy response and patient survival. Permutation tests validated the causal relationship between SE differences and disease phenotypes, while perturbation experiments revealed that FR keystone species exert disproportionate influence on the system's resilience.

Conclusions: Our SE-based approach to functional redundancy analysis provides superior sensitivity compared to conventional metrics by integrating multiple hierarchical levels of functional organization. This methodology establishes a novel perspective for understanding microbiome stability through personalized FR networks, positioning FRCs as promising diagnostic markers and therapeutic targets for microbiome-associated diseases. Video Abstract.

Background: Airborne microbial communities, although often challenging to study due to low biomass, play crucial roles in public health and pathogen transmission. Through shotgun metagenomics, this study utilizes non-invasive air sampling of face masks and aircraft cabin filters to investigate microbial diversity in environments with frequent human interactions, including hospitals and airplanes. A comprehensive sampling and analysis workflow was developed, incorporating environmental and enrichment protocols to enhance microbial DNA recovery and diversity profiling.

Results: Despite limitations in biomass, optimized extraction methods allowed for the successful identification of 407 species, with dominant taxa including Cutibacterium acnes, Staphylococcus epidermidis, Sphingomonas hankookensis, and Methylobacterium radiotolerans. Enrichment processing resulted in greater metagenome-assembled genome (MAG) recovery and higher antimicrobial resistance gene (ARG) identification.

Conclusions: The findings highlight the presence of ARGs in high-occupancy public spaces, suggesting the importance of monitoring and the potential for mitigating airborne transmission risks in such environments. This study demonstrates the utility of combining environmental and enrichment sampling to capture comprehensive microbial and ARG profiles in confined spaces, providing a framework for enhanced pathogen monitoring in public health contexts. Video Abstract.

Background: Aflatoxin B₁ (AFB₁), a highly carcinogenic and hepatotoxic mycotoxin frequently contaminating animal feed, presents serious health risks to both humans and livestock. Although AFB₁'s hepatotoxicity and other organ damage are extensively characterized, how this mycotoxin influences ruminal microbiota dynamics and functional activities in ruminants remains underexplored. Although some studies suggest that AFB₁ reduces nutrient digestibility and performance in ruminants, the underlying mechanisms are unclear. To aid in developing effective mitigation strategies for aflatoxicosis in ruminants, this study randomly divided Saanen goats into three groups. The CON group received the standard ration without additives, whereas LD and HD groups were provided identical basal diets fortified with 50 or 500 μg/kg AFB₁. Throughout the study, alterations in ruminal fermentation parameters, microbiome, and metabolome profiles were analyzed.

Results: With increasing AFB₁ levels, ruminal pH, the concentration of total volatile fatty acids (VFA), acetate, and propionate decreased quadratically, while butyrate decreased linearly. Metagenomic profiling indicated suppressed populations of Pelagibacter and Flavobacterium following AFB₁ exposure, contrasting with promoted growth of Cryptobacteroides. Additionally, seven carbohydrate-active enzymes (CAZymes), specifically GT92, GT20, CE7, GT32, GT35, GT57, and GT50, were found to be more prevalent in the rumen of the CON group. Statistically higher viral loads characterized the HD group when benchmarked against CON group. Metabolomics analysis identified 1197 differential metabolites among the CON, LD, and HD groups, including cytochalasin Ppho and chrysophanol, both known for their teratogenic properties and their ability to induce cell death.

Conclusions: This study indicates that dietary AFB₁ exposure can alter the ruminal microbial and metabolomic profiles, induce prophage activation, and impact carbohydrate degradation and microbial protein turnover. These alterations may contribute to reductions in ruminal pH and volatile fatty acid concentrations, thereby impairing feed digestibility and animal performance. The findings provide valuable insights into AFB₁'s effects on rumen health, and further investigations of these metabolic pathways may help develop precision interventions to mitigate AFB₁-induced rumen dysfunction and productivity losses. Video Abstract.