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Multiomics and quantitative modelling disentangle diet, host, and microbiota contributions to the host metabolome

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Title:Multiomics and quantitative modelling disentangle diet, host, and microbiota contributions to the host metabolome
Creators Name:Zimmermann-Kogadeeva, M., Bencivenga-Barry, N.A., Zimmermann, M., Bork, P. and Goodman, A.L.
Abstract:Dietary nutrients, host metabolism, and gut microbiota activity each influence the host’s metabolic phenotype; however, the interplay between these factors remains poorly understood. We employed tissue-resolved metabolomics in gnotobiotic mice carrying a synthetic human gut microbiota and germfree mice in two dietary conditions to develop an intestinal flux model that quantifies diet, host, and bacterial contributions to the levels of 2,700 intestinal metabolites. While diet was the main factor affecting metabolite profiles, we identified 1,117 potential microbial substrates and products in the gut. By integrating metagenomics and metatranscriptomics data into genome-scale enzymatic networks, we linked 202 potential substrate-product pairs by a single enzymatic reaction. We further identified bacterial species and enzymes that can explain the differential abundance of 13% of the identified microbial products between the mouse groups. This quantitative modelling approach paves the way for controlling an individual’s metabolic phenotype by modulating their gut microbiome composition and diet.
Keywords:Animals, Mice
Source:bioRxiv
Publisher:Cold Spring Harbor Laboratory Press
Article Number:2022.08.15.503927
Date:15 August 2022
Official Publication:https://doi.org/10.1101/2022.08.15.503927

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