Using the Collaborative Cross to identify the role of host genetics in defining the murine gut microbiome Institutional Repository Document uri icon

abstract

  • Abstract Background: The human gut microbiota is a complex community comprised of trillions of bacteria and is critical for the digestion and absorption of nutrients. Bacterial communities of the intestinal microbiota influence the development of several conditions and diseases. We studied the effect of host genetics on gut microbial composition using Collaborative Cross (CC) mice, a panel of genetically diverse mouse strains. CC mice are genetically diverse across strains, but genetically identical within a given strain allowing for repetition and deeper analysis than is possible with other collections of genetically diverse mice. Results: 16S rRNA from the feces of 167 mice from 28 different CC strains was sequenced and analyzed using the Qiime2 pipeline. We observed large variance in the bacterial composition across CC strains starting at the phylum level. Using bacterial composition data, we identified 26 significant Quantitative Trait Locus (QTL) linked to 23 genera on 15 different mouse chromosomes. Genes within these intervals were analyzed for significant association with pathways and the previously known human GWAS database using Enrichr and DAVID analysis. Multiple host genes involved in obesity, glucose homeostasis, immunity, neurological diseases, and many other protein-coding genes located in these regions may play roles in determining the composition of the gut microbiota. After the collection of feces used for sequencing, a subset of CC mice was infected with Salmonella Typhimurium. Using the infection outcome data, we correlated the increase in abundance of Genus Lachnospiraceae and decrease in Genus Parasutterella to positive health outcomes after infection. Machine learning classifiers accurately predicted the CC strain and the infection outcome using pre-infection bacterial composition data from the feces. Conclusion: Our study supports the hypothesis that multiple host genes influence the gut microbiome composition and homeostasis, and that certain organisms may influence health outcomes after S. Typhimurium infection.

altmetric score

  • 1.25

author list (cited authors)

  • Nagarajan, A., Scoggin, K., Gupta, J., Threadgill, D. W., & Andrews-Polymenis, H. L.

citation count

  • 0

complete list of authors

  • Nagarajan, Aravindh||Scoggin, Kristin||Gupta, Jyotsana||Threadgill, David W||Andrews-Polymenis, Helene L

Book Title

  • Research Square

publication date

  • April 2022