Research ArticleHost-Microbe Interactions

Host mitochondria influence gut microbiome diversity: A role for ROS

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Science Signaling  02 Jul 2019:
Vol. 12, Issue 588, eaaw3159
DOI: 10.1126/scisignal.aaw3159

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Inheriting microbiome variation

In mice, the bacterial species that persist within the gut microbiome are maternally inherited. However, maternally inherited variations in mitochondrial DNA (mtDNA) sequence also correlate with gut microbiome diversity, as well as the production of reactive oxygen species (ROS). In mice with mtDNA variants associated with increased production of ROS, Yardeni et al. found reduced gut microbiome species diversity. When pups were cross-fostered to unlink inheritance of mtDNA and gut microbiota, after weaning, the gut microbiome species were reflective of inherited mtDNA variation. Both pharmacological and genetic reduction of mitochondrial ROS abundance increased microbiome diversity. These data suggest that microbiome diversity is genetically encoded, and further imply that antioxidants may improve the efficacy of cancer immunotherapy, which is sensitive to microbiome composition.

Abstract

Changes in the gut microbiota and the mitochondrial genome are both linked with the development of disease. To investigate why, we examined the gut microbiota of mice harboring various mutations in genes that alter mitochondrial function. These studies revealed that mitochondrial genetic variations altered the composition of the gut microbiota community. In cross-fostering studies, we found that although the initial microbiota community of newborn mice was that obtained from the nursing mother, the microbiota community progressed toward that characteristic of the microbiome of unfostered pups of the same genotype within 2 months. Analysis of the mitochondrial DNA variants associated with altered gut microbiota suggested that microbiome species diversity correlated with host reactive oxygen species (ROS) production. To determine whether the abundance of ROS could alter the gut microbiota, mice were aged, treated with N-acetylcysteine, or engineered to express the ROS scavenger catalase specifically within the mitochondria. All three conditions altered the microbiota from that initially established. Thus, these data suggest that the mitochondrial genotype modulates both ROS production and the species diversity of the gut microbiome, implying that the connection between the gut microbiome and common disease phenotypes might be due to underlying changes in mitochondrial function.

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