| Title: | Causal relationships among the gut microbiome, short-chain fatty acids and metabolic diseases |
| Journal: | Nature Genetics |
| Published: | 18 Feb 2019 |
| Pubmed: | https://pubmed.ncbi.nlm.nih.gov/30778224/ |
| DOI: | https://doi.org/10.1038/s41588-019-0350-x |
| URL: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6441384 |
| Citations: | 970 (460 in last 2 years) as of 8 Aug 2024 |
Publication 8693
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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.</p>
17 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
1 Application
| Application ID | Title |
|---|---|
| 9161 | Type 2 diabetes: using genetic discovery to drive biological inference and translational opportunities. |
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