Microbiome最新文献

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Results: Based on previously published and unpublished datasets, 363 stream metagenomes were combined to build a comprehensive MAG and gene database from stream sediments and surface water including a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.

Background: Dental caries, a dysbiotic biofilm disease driven by polymicrobial acidogenesis, often coexists with type 2 diabetes (T2D). Previous studies suggest covarying relationships between circulating and salivary metabolites in patients with T2D. However, the role of hyperglycemia-induced saccharide migration from plasma to saliva in caries pathogenesis remains unclear. Here, we developed a novel method for untargeted metabolomics profiling of trace saliva from sublingual and submandibular glands, comparing this profile with those of plasma and whole saliva in participants with T2D (n = 31) and those with normoglycemia (n = 30). This comparison aimed to determine how circulating saccharide migration into the oral cavity and its subsequent microbial consumption are linked to dental caries. Additionally, shotgun metagenomic sequencing was combined with this analysis to investigate the cariogenic impact of circulating saccharide migration on the composition and function of supragingival biofilm using MetaPhlAn4 and HUMAnN3 pipelines.

Results: The metabolomics profiles of glandular saliva showed intermediate dissimilarity between plasma and whole saliva, reflecting cardiometabolic traits more sensitively than whole saliva. Glucose and fructose showed a decreasing positive correlation with glycemic parameters in the order of plasma, glandular saliva, and whole saliva, suggesting systemic-to-oral migration and subsequent microbial consumption. Saccharide migration was more pronounced in participants with dental caries and plaque accumulation, coinciding with shifts in supragingival microbiota, including depletion of Streptococcus sanguinis, Corynebacterium durum, and Rothia aeria, and enrichment of Streptococcus mutans, Veillonella parvula, and Actinomyces sp. oral taxon 448. Glycolytic potential increased at the community level. Improved glycemic control reduced fructose migration and mitigated dysbiosis, decreasing fructose phosphotransferase abundance and shifting the S. mutans-S. sanguinis balance. Experimental validation demonstrated that fructose promotes S. mutans dominance over S. sanguinis in dual-species biofilms.

Conclusions: This study establishes saccharide migration as a metabolic driver of supragingival dysbiosis in T2D. The findings highlight the role of both glucose and fructose in caries pathogenesis and suggest that glycemic control could serve as an effective strategy as part of caries control. Video Abstract.

Background: Bacterial cystitis, caused by Escherichia coli (E. coli), is a common urinary tract infection that frequently recurs and seriously affects patient health. Although it is known that gut dysbiosis increases susceptibility to recurrent urinary tract infections, its impact on non-complicated bacterial cystitis-the most common and primary form of urinary tract infection-remains uncertain.

Results: This study found that bacterial infection can cause long-term alterations in gut microbiota structure and affect the production of metabolites. Depletion of the gut microbiota worsens the inflammatory response to bacterial infection, disrupts the epithelial barrier of the bladder, and increases E. coli retention in the bladder and bloodstream. Fecal microbiota transplantation was found to significantly alleviate these excessive inflammatory responses. The study also identified that several tryptophan derivatives derived from the gut microbiota were significantly altered during bacterial microbiota depletion and bacterial infection, with indole-3-propionic acid (IPA) exhibiting the most significant alleviating effect on the excessive inflammatory response during infection. Additionally, the study demonstrated that transcriptional activation of the immune-inhibitory protein Prg4 is regulated by the IPA receptor AhR, which is expressed in bladder urothelial cells. Knockout of AhR in bladder urothelial reduced Prg4 expression and overactivated NF-κB signaling, resulting in the loss of the IPA-alleviating effect. This study suggests that the normal gut microbiota can activate AhR in bladder urothelial cells through its metabolite IPA, regulating the transcription of Prg4 and subsequently modulating the inflammatory response to bacterial cystitis caused by E. coli infection.

Conclusions: These findings provide a theoretical foundation for the clinical diagnosis and treatment of bacterial cystitis by leveraging the gut microbiota and their metabolites as promising therapeutic targets. Video Abstract.

Background: Quorum sensing is a fundamental chemical communication mechanism that enables microorganisms to coordinate behavior and adapt to environmental conditions. However, its contribution in deep-sea cold seep ecosystems, where diverse microbial communities and frequent communication occur, remains poorly understood. In this study, we aimed to elucidate the occurrence and potential ecological roles of quorum sensing in cold seeps.

Results: We analyzed 170 metagenomes and 33 metatranscriptomes from 17 global cold seep sites, identifying 299,355 quorum sensing genes from the cold seep non-redundant gene catalog. These genes represent 34 types across six quorum sensing systems, with distribution patterns influenced by sediment depth and seep type. A total of 32,500 quorum sensing genes were identified in 3576 metagenome-assembled genomes from 12 archaeal and 108 bacterial phyla, revealing a complex network of intraspecies and interspecies communication. Microbial groups involved in key metabolic processes, such as sulfate-reducing bacteria, anaerobic methanotrophic archaea, diazotrophs, and organohalide reducers, were extensively regulated by quorum sensing, influencing biogeochemical cycles in cold seeps. Phylogenetic analysis and protein domain identification highlighted the involvement of key quorum sensing-related proteins (e.g., PDE, RpfC/G, CahR, and LuxR) in modulating microbial behaviors, such as motility and chemotaxis. Heterologous expression further confirmed the activity of representative LuxI-R pairs, and metabolomic profiling suggested the presence of putative quorum sensing inhibitors in cold seep sediments.

Conclusions: Overall, these findings highlight the complexity and significance of quorum sensing in microbial interactions, ecological adaptation, and biogeochemical cycling within cold seep ecosystems, advancing our understanding of microbial communication in the deep biosphere. Video Abstract.

Background: Iron is essential for biological nitrogen removal in wastewater treatment plants (WWTPs), as a significant portion of microbial nitrogen-transforming enzymes require iron. However, iron bioavailability is a global challenge for nitrogen removal microbes in WWTPs, where it often exists in insoluble forms due to its complexation with various wastewater constituents.

Results: Combined laboratory experiment and metagenomic analysis of 52 global WWTPs, we found that siderophore-producing bacteria (SPB) were previously uncharacterized dominant members in activated sludge. SPB enhance the iron uptake of activated sludge microbial communities by facilitating the transport of iron ions from insoluble sources into the cells. Of the 1328 total recovered metagenome-assembled genomes (MAGs) from global WWTPs, 6.2% were identified as SPB, while 79.3% of MAGs could utilize siderophores, indicating widespread sharing of siderophores in WWTPs. Interestingly, nearly all ammonium-oxidizing bacteria (AOB) from WWTPs lacked siderophore-producing capacity, and exogenous siderophore (20 µM pyochelin) addition boosted ammonium oxidation rates by 28.2%. Moreover, strong indications were found for an association between AOB and the SPB in global WWTPs, suggesting their symbiotic interaction is a common and critical process to maintain ammonium oxidation performance. SPB in WWTPs were predominantly aerobic or facultative anaerobic heterotrophic bacteria, exhibiting low taxonomic diversity but high abundance.

Conclusions: This study reveals SPB as previously overlooked but crucial contributors to biological nitrogen removal in global WWTPs, providing foundational insights into iron-based microbial cooperation within engineered systems. Modulating SPB activity based on their metabolic characteristics is a promising strategy to cope with low iron bioavailability issue for biological processes in WWTPs. Video Abstract.

Background: Plasmids are influential drivers of bacterial evolution, facilitating horizontal gene transfer and shaping microbial communities. Current knowledge on plasmid persistence and mobilization in natural environments is derived from community-level studies, neglecting the single-cell level, where these dynamic processes unfold. Pinpointing specific plasmids within their natural environments is essential to unravel the dynamics between plasmids and their bacterial hosts.

Results: Here, we overcame the technical hurdle of natural plasmid detectability in single cells by developing SPEci-FISH (Short Probe EffiCIent Fluorescence In Situ Hybridization), a novel molecular method designed to detect and visualize plasmids, regardless of their copy number, directly within bacterial cells, enabling their precise identification at the single-cell level. To complement this method, we created ProFiT (PRObe FInding Tool), a program facilitating the design of sequence-based probes for targeting individual plasmids or plasmid families.

Conclusions: We have successfully applied these methods, combined with high-resolution microscopy, to investigate the dispersal and localization of natural plasmids within a clinical isolate, revealing various plasmid spatial patterns within the same bacterial population. Importantly, bridging the technological gap in linking plasmids to hosts in native complex microbial environments, we demonstrated that our method, when combined with fluorescence-activated cell sorting (FACS), can track plasmid-host dynamics in a human fecal sample. This approach identified multiple potential bacterial hosts for a conjugative plasmid that we assembled from this fecal sample's metagenome. Our integrated approach offers a significant advancement toward understanding plasmid ecology in complex microbiomes. Video Abstract.