Dataset Information

Mitochondrial gene polymorphism is associated with gut microbial communities in mice.

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.

SUBMITTER: Hirose M

PROVIDER: S-EPMC5681637 | biostudies-literature | 2017 Nov

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Mitochondrial gene polymorphism is associated with gut microbial communities in mice.

Hirose Misa M Künstner Axel A Schilf Paul P Sünderhauf Annika A Rupp Jan J Jöhren Olaf O Schwaninger Markus M Sina Christian C Baines John F JF Ibrahim Saleh M SM

Scientific reports 20171110 1

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 mu ...[more]

PMID: 29127319

Similar Datasets

Project description:Fluoridation of drinking water and dental products prevents dental caries primarily by inhibiting energy harvest in oral cariogenic bacteria (such as Streptococcus mutans and Streptococcus sanguinis), thus leading to their depletion. However, the extent to which oral and gut microbial communities are affected by host fluoride exposure has been underexplored. In this study, we modeled human fluoride exposures to municipal water and dental products by treating mice with low or high levels of fluoride over a 12-week period. We then used 16S rRNA gene amplicon and shotgun metagenomic sequencing to assess fluoride's effects on oral and gut microbiome composition and function. In both the low- and high-fluoride groups, several operational taxonomic units (OTUs) belonging to acidogenic bacterial genera (such as Parabacteroides, Bacteroides, and Bilophila) were depleted in the oral community. In addition, fluoride-associated changes in oral community composition resulted in depletion of gene families involved in central carbon metabolism and energy harvest (2-oxoglutarate ferredoxin oxidoreductase, succinate dehydrogenase, and the glyoxylate cycle). In contrast, fluoride treatment did not induce a significant shift in gut microbial community composition or function in our mouse model, possibly due to absorption in the upper gastrointestinal tract. Fluoride-associated perturbations thus appeared to have a selective effect on the composition of the oral but not gut microbial community in mice. Future studies will be necessary to understand possible implications of fluoride exposure for the human microbiome. IMPORTANCE Fluoride has been added to drinking water and dental products since the 1950s. The beneficial effects of fluoride on oral health are due to its ability to inhibit the growth of bacteria that cause dental caries. Despite widespread human consumption of fluoride, there have been only two studies of humans that considered the effect of fluoride on human-associated microbial communities, which are increasingly understood to play important roles in health and disease. Notably, neither of these studies included a true cross-sectional control lacking fluoride exposure, as study subjects continued baseline fluoride treatment in their daily dental hygiene routines. To our knowledge, this work (in mice) is the first controlled study to assess the independent effects of fluoride exposure on the oral and gut microbial communities. Investigating how fluoride interacts with host-associated microbial communities in this controlled setting represents an effort toward understanding how common environmental exposures may potentially influence health.

Project description:BackgroundAnalyses of gut microbiome composition in livestock species have shown its potential to contribute to the regulation of complex phenotypes. However, little is known about the host genetic control over the gut microbial communities. In pigs, previous studies are based on classical "single-gene-single-trait" approaches and have evaluated the role of host genome controlling gut prokaryote and eukaryote communities separately.ResultsIn order to determine the ability of the host genome to control the diversity and composition of microbial communities in healthy pigs, we undertook genome-wide association studies (GWAS) for 39 microbial phenotypes that included 2 diversity indexes, and the relative abundance of 31 bacterial and six commensal protist genera in 390 pigs genotyped for 70 K SNPs. The GWAS results were processed through a 3-step analytical pipeline comprised of (1) association weight matrix; (2) regulatory impact factor; and (3) partial correlation and information theory. The inferred gene regulatory network comprised 3561 genes (within a 5 kb distance from a relevant SNP-P < 0.05) and 738,913 connections (SNP-to-SNP co-associations). Our findings highlight the complexity and polygenic nature of the pig gut microbial ecosystem. Prominent within the network were 5 regulators, PRDM15, STAT1, ssc-mir-371, SOX9 and RUNX2 which gathered 942, 607, 588, 284 and 273 connections, respectively. PRDM15 modulates the transcription of upstream regulators of WNT and MAPK-ERK signaling to safeguard naive pluripotency and regulates the production of Th1- and Th2-type immune response. The signal transducer STAT1 has long been associated with immune processes and was recently identified as a potential regulator of vaccine response to porcine reproductive and respiratory syndrome. The list of regulators was enriched for immune-related pathways, and the list of predicted targets includes candidate genes previously reported as associated with microbiota profile in pigs, mice and human, such as SLIT3, SLC39A8, NOS1, IL1R2, DAB1, TOX3, SPP1, THSD7B, ELF2, PIANP, A2ML1, and IFNAR1. Moreover, we show the existence of host-genetic variants jointly associated with the relative abundance of butyrate producer bacteria and host performance.ConclusionsTaken together, our results identified regulators, candidate genes, and mechanisms linked with microbiome modulation by the host. They further highlight the value of the proposed analytical pipeline to exploit pleiotropy and the crosstalk between bacteria and protists as significant contributors to host-microbiome interactions and identify genetic markers and candidate genes that can be incorporated in breeding program to improve host-performance and microbial traits. Video Abstract.

Dataset Information

Mitochondrial gene polymorphism is associated with gut microbial communities in mice.

Publications

Mitochondrial gene polymorphism is associated with gut microbial communities in mice.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets