Causal relationships among the gut microbiome, short-chain fatty acids and metabolic diseases View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2019-02-18

AUTHORS

Serena Sanna, Natalie R. van Zuydam, Anubha Mahajan, Alexander Kurilshikov, Arnau Vich Vila, Urmo Võsa, Zlatan Mujagic, Ad A. M. Masclee, Daisy M. A. E. Jonkers, Marije Oosting, Leo A. B. Joosten, Mihai G. Netea, Lude Franke, Alexandra Zhernakova, Jingyuan Fu, Cisca Wijmenga, Mark I. McCarthy

ABSTRACT

Microbiome-wide association studies on large population cohorts have highlighted associations between the gut microbiome and complex traits, including type 2 diabetes (T2D) and obesity1. However, the causal relationships remain largely unresolved. We leveraged information from 952 normoglycemic individuals for whom genome-wide genotyping, gut metagenomic sequence and fecal short-chain fatty acid (SCFA) levels were available2, then combined this information with genome-wide-association summary statistics for 17 metabolic and anthropometric traits. Using bidirectional Mendelian randomization (MR) analyses to assess causality3, we found that the host-genetic-driven increase in gut production of the SCFA butyrate was associated with improved insulin response after an oral glucose-tolerance test (P = 9.8 × 10−5), whereas abnormalities in the production or absorption of another SCFA, propionate, were causally related to an increased risk of T2D (P = 0.004). These data provide evidence of a causal effect of the gut microbiome on metabolic traits and support the use of MR as a means to elucidate causal relationships from microbiome-wide association findings. More... »

PAGES

600-605

References to SciGraph publications

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  • Journal

    TITLE

    Nature Genetics

    ISSUE

    4

    VOLUME

    51

    Identifiers

    URI

    http://scigraph.springernature.com/pub.10.1038/s41588-019-0350-x

    DOI

    http://dx.doi.org/10.1038/s41588-019-0350-x

    DIMENSIONS

    https://app.dimensions.ai/details/publication/pub.1112198834

    PUBMED

    https://www.ncbi.nlm.nih.gov/pubmed/30778224


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