Murine Genetic Background Overcomes Gut Microbiota Changes to Explain Metabolic Response to High-Fat Diet.

Zahra Safari,Kurt Zatloukal,Aurélia Bruneau,Philippe Gérard,Magali Monnoye,Mahendra Mariadassou,Catherine Philippe

doi:10.3390/nu12020287

Abstract

Interactions of diet, gut microbiota, and host genetics play essential roles in the development of metabolic diseases. A/J and C57BL/6J (C57) are two mouse strains known to display different susceptibilities to metabolic disorders. In this context, we analyzed gut microbiota composition in A/J and C57 mice, and assessed its responses to high-fat diet (HFD) and antibiotic (AB) treatment. We also exchanged the gut microbiota between the two strains following AB treatment to evaluate its impact on the metabolism. We showed that A/J and C57 mice have different microbiome structure and composition at baseline. Moreover, A/J and C57 microbiomes responded differently to HFD and AB treatments. Exchange of the gut microbiota between the two strains was successful as recipients’ microbiota resembled donor-strain microbiota. Seven weeks after inoculation, the differences between recipients persisted and were still closer from the donor-strain microbiota. Despite effective microbiota transplants, the response to HFD was not markedly modified in C57 and A/J mice. Particularly, body weight gain and glucose intolerance in response to HFD remained different in the two mouse strains whatever the changes in microbiome composition. This indicated that genetic background has a much stronger impact on metabolic responses to HFD than gut microbiome composition.

Highlights

Non-alcoholic fatty liver disease (NAFLD) is the most common disease among chronic liver disorders in developed and developing countries [1]
Its composition is impacted throughout life by host genetics and environmental factors including diet, antibiotics, and disease states [26,27]
Studies showed that different mouse strains, and mice from different suppliers display distinct susceptibilities to obesity and diabetes when challenged with an high-fat diet (HFD) [28,29] highlighting the role of both genetics and environment in host metabolism

Summary

Introduction

Non-alcoholic fatty liver disease (NAFLD) is the most common disease among chronic liver disorders in developed and developing countries [1]. NAFLD includes a clinicopathologic spectrum of diseases ranging from simple hepatic steatosis to nonalcoholic steatohepatitis (NASH) that may progress to cirrhosis and cirrhosis-related complications, including hepatocellular carcinoma (HCC). It is strongly correlated with obesity, insulin resistance (IR), and type 2 diabetes mellitus. The role of the gut microbiome in obesity [3] and in NAFLD [4] has been revealed. There is evidence that the gut microbiome plays a role as a link between genetic and phenotypic diversity among genetically different mouse strains in response to dietary challenges [5,6]

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