Abstract
BackgroundConsistent compositional shifts in the gut microbiota are observed in IBD and other chronic intestinal disorders and may contribute to pathogenesis. The identities of microbial biomolecular mechanisms and metabolic products responsible for disease phenotypes remain to be determined, as do the means by which such microbial functions may be therapeutically modified.ResultsThe composition of the microbiota and metabolites in gut microbiome samples in 47 subjects were determined. Samples were obtained by endoscopic mucosal lavage from the cecum and sigmoid colon regions, and each sample was sequenced using the 16S rRNA gene V4 region (Illumina-HiSeq 2000 platform) and assessed by UPLC mass spectroscopy. Spearman correlations were used to identify widespread, statistically significant microbial-metabolite relationships. Metagenomes for identified microbial OTUs were imputed using PICRUSt, and KEGG metabolic pathway modules for imputed genes were assigned using HUMAnN. The resulting metabolic pathway abundances were mostly concordant with metabolite data. Analysis of the metabolome-driven distribution of OTU phylogeny and function revealed clusters of clades that were both metabolically and metagenomically similar.ConclusionsThe results suggest that microbes are syntropic with mucosal metabolome composition and therefore may be the source of and/or dependent upon gut epithelial metabolites. The consistent relationship between inferred metagenomic function and assayed metabolites suggests that metagenomic composition is predictive to a reasonable degree of microbial community metabolite pools. The finding that certain metabolites strongly correlate with microbial community structure raises the possibility of targeting metabolites for monitoring and/or therapeutically manipulating microbial community function in IBD and other chronic diseases.
Highlights
Consistent compositional shifts in the gut microbiota are observed in inflammatory bowel disease (IBD) and other chronic intestinal disorders and may contribute to pathogenesis
To measure the composition, function and interdependence of the colonic microbiome and metabolome, a serial cross-sectional study was performed on human subjects undergoing screening colonic endoscopy: 93 mucosal water-lavage samples from the sigmoid and cecum regions of 47 subjects between the ages of 20 and 83 years (Table 1)
Phylotypic analysis revealed the relative abundance of 2,473 cecum and 2,595 sigmoid GreenGenes reference database-picked operational taxonomic unit (OTU) binned at 97% sequence similarity, and thresholded on detection in at least two samples
Summary
Consistent compositional shifts in the gut microbiota are observed in IBD and other chronic intestinal disorders and may contribute to pathogenesis. In twin-pair studies, Crohn’s disease-associated differences in fecal metabolites have been detected in parallel with microbial compositional and metagenomic differences in this compartment, and represented biomarkers related to disease state, presumably in part as products of the disease-associated changes in microbial metagenomic function [22,23,24]. Identification of such relationships is fundamental for interventional strategies to alter microbiota composition in the context of dysbiosis, and have been highlights of recent landmark studies of environment and diet in human fecal microbial composition [11,16,25]. Direct analysis of metabolic output by and interactions between microbial species is a burgeoning investigative field, but challenging methodologically, in vivo [26,27]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
