Project description:Gut microbiome research is rapidly moving towards the functional characterization of the microbiota by means of shotgun meta-omics. Here, we selected a cohort of healthy subjects from an indigenous and monitored Sardinian population to analyze their gut microbiota using both shotgun metagenomics and shotgun metaproteomics. We found a considerable divergence between genetic potential and functional activity of the human healthy gut microbiota, in spite of a quite comparable taxonomic structure revealed by the two approaches. Investigation of inter-individual variability of taxonomic features revealed Bacteroides and Akkermansia as remarkably conserved and variable in abundance within the population, respectively. Firmicutes-driven butyrogenesis (mainly due to Faecalibacterium spp.) was shown to be the functional activity with the higher expression rate and the lower inter-individual variability in the study cohort, highlighting the key importance of the biosynthesis of this microbial by-product for the gut homeostasis. The taxon-specific contribution to functional activities and metabolic tasks was also examined, giving insights into the peculiar role of several gut microbiota members in carbohydrate metabolism (including polysaccharide degradation, glycan transport, glycolysis and short-chain fatty acid production). In conclusion, our results provide useful indications regarding the main functions actively exerted by the gut microbiota members of a healthy human cohort, and support metaproteomics as a valuable approach to investigate the functional role of the gut microbiota in health and disease.
Project description:A recently layer of gene expression regulation is N6-methyladenosine (m6A) mRNA modification. The role of gut microbiota in modulating host m6A epitranscriptomic and gene expression has not been studied. To decipher the role of gut microbiome, we profiled m6A mRNA modification epitranscriptomic mark in conventional mice compared to germ free mice. Transcriptome-wide mapping of host m6A mRNA modifications in four mice tissues allowed us to discover that gut microbiota can greatly impact host m6A mRNA modifications. The expression levels of m6A writers in mice tissues are regulated by gut microbiota. In conclusion, we report transcriptome-wide mapping of host m6A mRNA modifications regulated by gut microbiota. The present study can help better understand the role of the microbiome in host gene expression and host-microbiome interactions.
Project description:Gut microbiota were assessed in 540 colonoscopy-screened adults by 16S rRNA gene sequencing of stool samples. Investigators compared gut microbiota diversity, overall composition, and normalized taxon abundance among these groups.
Project description:The gut microbiota exerts a profound influence on host physiology, but its systemic impact on gene expression across diverse tissues remains poorly characterized. This study investigated the transcriptional effects of gut microbiota depletion and restoration in mice across six tissues (colon, jejunum, liver, heart, lung, and kidney) using whole-transcriptome sequencing. We found that the presence of gut microbiota significantly altered the transcriptome, with the most pronounced effects in the colon. Using a linear mixed-effects model, we identified 7,365 effector genes. Tissue-specific analysis revealed that these genes were associated with distinct functional pathways, such as immunity in the gut and lung, and metabolism in the liver. Further refinement with LASSO regression pinpointed gut microbiota-mediated key effector genes, whose expression levels were significantly associated with patient survival in corresponding human cancers (e.g., LIHC, LUAD, KIRC). Furthermore, we observed a widespread remodeling of competing endogenous RNA (ceRNA) networks by the gut microbiota. Single-cell data analysis highlighted a potential gut-liver axis interaction, primarily mediated by colonic enterocytes and hepatic cholangiocytes, meanwhile gut microbiota repressed the transcription initiation of Noct in colonic enterocytes, whose expression level was significantly negatively correlated to gut-liver axis interaction. Our findings provide a comprehensive map of the multi-tissue transcriptional landscape shaped by the gut microbiota, revealing tissue-specific regulatory mechanisms and identifying key genes with potential clinical relevance in cancer.
Project description:Parkinson's disease (PD) is a common neurodegenerative disease in middle-aged and elderly people. The disorder of gut microbiota is involved in the pathophysiological process of various neurological diseases, and many studies have confirmed that gut microbiota is involved in the progression of PD. As one of the most effective methods to reconstruct gut microbiota, fecal microbiota transplantation (FMT) has been considered as an important treatment for PD. However, the mechanism of FMT treatment for PD is still lacking, which requires further exploration and can facilitate the application of FMT. As a model organism, Drosophila is highly conserved with mammalian system in maintaining intestinal homeostasis. In this study, there were significant differences in the gut microbiota of conventional Drosophila colonized from PD patients compared to those transplanted from normal controls. And we constructed rotenone-induced PD model in Drosophila followed by FMT in different groups, and investigated the impact of gut microbiome on transcriptome of the PD host. Microbial analysis by 16S rDNA sequencing showed that gut microbiota could affect bacterial structure of PD, which was confirmed by bacterial colonization results. In addition, transcriptome data suggested that gut microbiota can influence gene expression pattern of PD. Further experimental validations confirmed that lysosome and neuroactive ligand-receptor interaction are the most significantly influenced functional pathways by PD-derived gut microbiota. In summary, our data reveals the influence of PD-derived gut microbiota on host transcriptome and helps better understanding the interaction between gut microbiota and PD through gut-brain axis. The present study will facilitate the understanding of the mechanism underlying PD treatment with FMT in clinical practice.