Host genetic control of gut microbiome composition

The gut microbiome plays a significant role in health and disease, and there is mounting evidence indicating that the microbial composition is regulated in part by host genetics. Heritability estimates for microbial abundance in mice and humans range from (0.05–0.45), indicating that 5–45% of inter-...

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Published in:Mammalian genome Vol. 32; no. 4; pp. 263 - 281
Main Authors: Bubier, Jason A., Chesler, Elissa J., Weinstock, George M.
Format: Journal Article
Language:English
Published: New York Springer US 01.08.2021
Springer Nature B.V
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ISSN:0938-8990, 1432-1777, 1432-1777
Online Access:Get full text
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Summary:The gut microbiome plays a significant role in health and disease, and there is mounting evidence indicating that the microbial composition is regulated in part by host genetics. Heritability estimates for microbial abundance in mice and humans range from (0.05–0.45), indicating that 5–45% of inter-individual variation can be explained by genetics. Through twin studies, genetic association studies, systems genetics, and genome-wide association studies (GWAS), hundreds of specific host genetic loci have been shown to associate with the abundance of discrete gut microbes. Using genetically engineered knock-out mice, at least 30 specific genes have now been validated as having specific effects on the microbiome. The relationships among of host genetics, microbiome composition, and abundance, and disease is now beginning to be unraveled through experiments designed to test causality. The genetic control of disease and its relationship to the microbiome can manifest in multiple ways. First, a genetic variant may directly cause the disease phenotype, resulting in an altered microbiome as a consequence of the disease phenotype. Second, a genetic variant may alter gene expression in the host, which in turn alters the microbiome, producing the disease phenotype. Finally, the genetic variant may alter the microbiome directly, which can result in the disease phenotype. In order to understand the processes that underlie the onset and progression of certain diseases, future research must take into account the relationship among host genetics, microbiome, and disease phenotype, and the resources needed to study these relationships.
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ISSN:0938-8990
1432-1777
1432-1777
DOI:10.1007/s00335-021-09884-2