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.

• Nature Genetics
• NRC.nl