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

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 in...

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Vydané v:	Nature genetics Ročník 51; číslo 4; s. 600 - 605
Hlavní autori:	Sanna, Serena, van Zuydam, Natalie R., Mahajan, Anubha, Kurilshikov, Alexander, Vich Vila, Arnau, Võsa, Urmo, Mujagic, Zlatan, Masclee, Ad A. M., Jonkers, Daisy M. A. E., Oosting, Marije, Joosten, Leo A. B., Netea, Mihai G., Franke, Lude, Zhernakova, Alexandra, Fu, Jingyuan, Wijmenga, Cisca, McCarthy, Mark I.
Médium:	Journal Article
Jazyk:	English
Vydavateľské údaje:	New York Nature Publishing Group US 01.04.2019 Nature Publishing Group
Predmet:	45 631/208 692/308/174 692/699/2743/137 692/699/2743/393 Abnormalities Adolescent Adult Aged Aged, 80 and over Agriculture Animal Genetics and Genomics Anthropometry Biomedical and Life Sciences Biomedicine Cancer Research Chains Consortia Diabetes Diabetes mellitus Diabetes mellitus (non-insulin dependent) Diabetes Mellitus, Type 2 - genetics Digestive system Disease Esters Fatty acids Fatty Acids, Volatile - genetics Feces Female Gastrointestinal Microbiome - genetics Gene Function Genetic research Genomes Genomics Genotype Genotyping Glucose Glucose tolerance Glucose Tolerance Test - methods Gut microbiota Human Genetics Humans Insulin Intestinal microflora Letter Male Metabolic diseases Metabolic Diseases - genetics Metabolic disorders Metabolism Microbiomes Microbiota Microbiota (Symbiotic organisms) Middle Aged Netherlands Nucleotide sequence Obesity Population studies Principal components analysis Production capacity Propionic acid Statistics Studies Type 2 diabetes Young Adult Netherlands United Kingdom > UK
ISSN:	1061-4036, 1546-1718, 1546-1718
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Shrnutí:	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.
Bibliografia:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 14 content type line 23
ISSN:	1061-4036 1546-1718 1546-1718
DOI:	10.1038/s41588-019-0350-x