Mitochondrial gene polymorphism is associated with gut microbial communities in mice - PubMed (original) (raw)

Mitochondrial gene polymorphism is associated with gut microbial communities in mice

Misa Hirose et al. Sci Rep. 2017.

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-mt FVB/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-mt FVB/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.

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Conflict of interest statement

The authors declare that they have no competing interests.

Figures

Figure 1

Figure 1

The ratio of Firmicutes and Bacteroidetes significantly differs between conplastic strains. *P = 0.0230 (Kruskal-Wallis test), *P < 0.05 (Dunn test). B6, C57BL/6J; FVB, C57BL/6J-mt FVB/NJ; NZB, C57BL/6J-mt NZB/BlnJ.

Figure 2

Figure 2

Beta diversity of gut microbiota in conplastic strains. (A) Principal coordinate analysis (PCoA) on unweighted UniFrac distance. (B) Capscale plot on unweighted UniFrac distance. Strain was taken as constraint, and correction for sex effect was applied. The CAP1 and CAP2 were found to be significant with respect to strain with 999 permutations (P = 0.001 for CAP1 and CAP2).

Figure 3

Figure 3

Reduced oxygen consumption levels and Increased levels of glycolysis in primary lymphocytes isolated from C57BL/6J-mt FVB/NJ compared with cells from C57BL/6J. (A) The oxygen consumption ratio (OCR) was measured in the primary lymphocytes from peripheral lymph nodes. Basal respiration and ATP production levels were significantly less in C57BL/6J-mt FVB/NJ compared to C57BL/6J. (B) The extracellular acidification rate (ECAR), which indicates glycolysis levels, in the primary lymphocytes was measured using a Seahorse XF analyzer. Data presented in the graph was normalized with the value of C57BL/6J. B6: C57BL/6J, FVB: C57BL/6J-mt FVB/NJ. ***P < 0.001, t test.

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