Mitochondrial gene polymorphism is associated with gut microbial communities in mice

Misa Hirose,Annika Sünderhauf,John F Baines,Markus Schwaninger,Olaf Jöhren,Jan Rupp,Saleh M Ibrahim,Paul Schilf,Christian Sina,Axel Künstner

doi:10.1038/s41598-017-15377-7

Abstract

Gut microbial communities are key mediators of health and disease and have the capacity to drive the pathogenesis of diverse complex diseases including metabolic and chronic inflammatory diseases as well as aging. Host genetics is also a major determinant of disease phenotypes, whereby two different genomes play a role, the nuclear (nDNA)- and mitochondrial genome (mtDNA). We investigated the impact of mutations in mtDNA on the gut microbiota using conplastic mouse strains exhibiting distinct mutations in their mtDNA on an identical nDNA. Each of three strain tested harbors a distinct gut microbiota, ranging from differences at the phylum- to operational taxonomic units level. The C57BL/6J-mtFVB/NJ strain, carrying a mutation in the mitochondrial ATP8 synthase gene, exhibits higher Firmicutes abundance than Bacteroidetes, indicating a possible indicative for metabolic dysfunctions. In line with this, the C57BL/6J-mtFVB/NJ displays a variety of different phenotypes, including increased susceptibility to metabolic-related and inflammatory disorders. Furthermore, we discuss the cross-talk between mitochondrial genome/mitochondria and commensal microbiota in relation to clinical phenotypes. In summary, we demonstrate that mutations in mtDNA lead to significant differences in the composition of gut microbial communities in mice. Such differences may facilitate the emergence of metabolic disease and therefore constitute potential therapeutic targets.

Highlights

In recent years a pivotal role of the host-associated microbiota in the emergence of chronic diseases has become apparent, largely due to the realization that these communities are much more variable among individuals than previously anticipated[1]
We provide the first direct evidence that mutations in the mitochondrial genes significantly impact the composition of the gut microbial community in mice
Among several mitochondrial genes participating in this regulation, the mt-Atp[8] appears to be of particular importance, as the mutation

Summary

Introduction

In recent years a pivotal role of the host-associated microbiota in the emergence of chronic diseases has become apparent, largely due to the realization that these communities are much more variable among individuals than previously anticipated[1]. Mutations in the mtDNA impact OXPHOS functions, including adenosine triphosphate (ATP) production, reactive oxygen species (ROS) production and mitochondrial membrane potential. These all contribute to pivotal cellular activities, such as cell activation, proliferation and cell death[9]. While differences are apparent according to region-defined haplogroups (Europeans, Asian, and Mexican Americans), non-haplogroup defining single nucleotide polymorphism (SNP) could not be clearly associated to variation in microbial communities This limitation is in part due to the parallel impact of the highly variable nuclear genome on the composition of the gut microbiota[24], making it difficult to reveal the effect of mitochondrial polymorphism

Methods

Results

Conclusion