Gut microbiome mediates host genomic effects on phenotypes: a case study with fat deposition in pigs.

Francesco Tiezzi,Justin Fix,Christian Maltecca,Caleb Shull,Clint Schwab

doi:10.1016/j.csbj.2020.12.038

Abstract

A large number of studies have highlighted the importance of gut microbiome composition in shaping fat deposition in mammals. Several studies have also highlighted how host genome controls the abundance of certain species that make up the gut microbiota. We propose a systematic approach to infer how the host genome can control the gut microbiome, which in turn contributes to the host phenotype determination. We implemented a mediation test that can be applied to measured and latent dependent variables to describe fat deposition in swine (Sus scrofa). In this study, we identify several host genomic features having a microbiome-mediated effects on fat deposition. This demonstrates how the host genome can affect the phenotypic trait by inducing a change in gut microbiome composition that leads to a change in the phenotype. Host genomic variants identified through our analysis are different than the ones detected in a traditional genome-wide association study. In addition, the use of latent dependent variables allows for the discovery of additional host genomic features that do not show a significant effect on the measured variables. Microbiome-mediated host genomic effects can help understand the genetic determination of fat deposition. Since their contribution to the overall genetic variance is usually not included in association studies, they can contribute to filling the missing heritability gap and provide further insights into the host genome - gut microbiome interplay. Further studies should focus on the portability of these effects to other populations as well as their preservation when pro-/pre-/anti-biotics are used (i.e. remediation).

Highlights

A vast body of literature exists in both plants and livestock on discovering genomic (G) variants with a significant effect on a variety of phenotypes (P) of interest.Recently, an increasing number of studies have started focusing on the impact of the gut microbiome (M) on phenotypic performance [54,53,17], where gut microbiome is expressed as the relative abundance of microbial features such as genes, taxa and biological function, etc.In some of these studies, an additional step in which G variants are tested for their association with M features is presented [9,64,10]
In this study we propose a simple method to study the causal relationships between host genome, gut microbiome and host phenotypes
We used a dataset that included information collected on swine (Sus scrofa) where different measures of fat deposition served as phenotypes of interest

Summary

Introduction

An increasing number of studies have started focusing on the impact of the gut microbiome (M) on phenotypic performance [54,53,17], where gut microbiome is expressed as the relative abundance of microbial features such as genes, taxa and biological function, etc In some of these studies, an additional step in which G variants are tested for their association with M features is presented [9,64,10].

Objectives

Methods

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Discussion

Conclusion