Integrative Analysis of the Microbiome and Metabolome of the Human Intestinal Mucosal Surface Reveals Exquisite Inter-relationships

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A fascinating open paper was published in microbiome in 2013, and its suggested conclusions are now more prescient than ever, as the relationship between genotype, phenotype, and metabolic repertoire in the microbiome is understood to be non-linear.[1] The requirement for a certain functional diversity to ensure a well-functioning cooperative intestinal microbiota is crucial to break down various complex dietary compounds and divide metabolic tasks among different community members.

This circumstance can be regarded as an important evolutionary and ecological feature of the microbiome; functional components constituting whole pathways can be very different within closely related species, whereas the metabolism in the overall metabolic repertoire is limited. In other words, by dividing the metabolic tasks between certain taxonomic groups, the microbiota can make efficient use out of a small set of functions thereby facilitating niche partitioning. This comprehension has important implications when considering the overall species richness of the human gut microbiome in the context of different patients and diseases.


Consistent 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.


The 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.


The 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.


In effect the proposal here is that by inducing the production of short chain fatty acids, the most abundant of the metabolically active metabolites, gene pool transfer and niche skill set development can be induced even in small population groups to manage important metabolic functions, including the coding of immune responses. Food is the most efficient method for induction of SCFAs and the enhancement of key stone species.


[1] McHardy IH, Goudarzi M, Tong M, Ruegger PM, Schwager E, Weger JR, Graeber TG, Sonnenburg JL, Horvath S, Huttenhower C, McGovern DP, Fornace AJ Jr, Borneman J, Braun J. Integrative analysis of the microbiome and metabolome of the human intestinal mucosal surface reveals exquisite inter-relationships. Microbiome. 2013 Jun 5;1(1):17. View Full Paper

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