Key Publication: Causal relationships among the gut microbiome, short-chain fatty acids and metabolic diseases: Nature Genetics
Causal relationships among the gut microbiome, short-chain fatty acids and metabolic diseases
- Sanna S
- van Zuydam NR
- Mahajan A
- Kurilshikov A
- Vich Vila A
- Võsa U
- Mujagic Z
- Masclee AAM
- Jonkers DMAE
- Oosting M
- Joosten LAB
- Netea MG
- Franke L
- Zhernakova A
- Fu J
- Wijmenga C
- McCarthy MI
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 obesity . 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 , 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 , 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.
| Last modified: | 20 February 2019 4.27 p.m. |
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