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Causal relationships among the gut microbiome, short-chain fatty acids and metabolic diseases
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Journal Article
Causal relationships among the gut microbiome, short-chain fatty acids and metabolic diseases
2019
Overview
Microbiome-wide association studies on large population cohorts have highlighted associations between the gut microbiome and complex traits, including type 2 diabetes (T2D) and obesity
1
. 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 available
2
, then combined this information with genome-wide-association summary statistics for 17 metabolic and anthropometric traits. Using bidirectional Mendelian randomization (MR) analyses to assess causality
3
, 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.
Mendelian randomization analyses using genotyping data, gut metagenomic sequence and fecal short-chain-fatty-acid levels from 952 individuals combined with GWAS data show evidence of a causal effect of the gut microbiome on metabolic traits.
Publisher
Nature Publishing Group US,Nature Publishing Group
Subject
/ 631/208
/ Adult
/ Aged
/ Animal Genetics and Genomics
/ Biomedical and Life Sciences
/ Chains
/ Diabetes
/ Diabetes mellitus (non-insulin dependent)
/ Diabetes Mellitus, Type 2 - genetics
/ Disease
/ Esters
/ Fatty Acids, Volatile - genetics
/ Feces
/ Female
/ Gastrointestinal Microbiome - genetics
/ Genomes
/ Genomics
/ Genotype
/ Glucose
/ Glucose Tolerance Test - methods
/ Humans
/ Insulin
/ Letter
/ Male
/ Metabolic Diseases - genetics
/ Microbiota (Symbiotic organisms)
/ Obesity
/ Principal components analysis
/ Studies
