The human intestinal microbiota is one of the densest microbial ecosystems on earth, containing approximately 1012 organisms per gram of colonic contents and is composed of hundreds of different species. In recent years, the topic of the intestinal microbiota has gained much interest by the worldwide scientific community, and here in the United States, the National Insitutes of Health has made tremendous investments in studying the human microbiome. Despite the heightened interest in the intestinal microbiota, understanding of the dynamic microbial interactions that occur within this ecosystem is still in its infancy.

For example, there is much to be further understood about how bacterial species become established in the mammalian intestine, the interactions that occur between competing species, and the factors that influence microbial stability and diversity in the ecosystem. The Comstock laboratory studies the basic biology of a prominant order of bacteria of the human intestine, the Bacteroidales. These are the most abundant Gram-negative bacteria of this ecosystem, and they establish mutualistic relationships with their human hosts whereby both receive benefits. We study various molecular biological aspects of the Bacteroidales that allow them to survive and thrive in the human gut. We are also very interested in the population and community dynamics of the intestinal microbiota, such as how these bacteria interact among themselves and with other members of the intestinal microbiota, and how community stability is acheived and maintained. These studies are an essential prerequisite to understanding how the instestinal microbiota provides beneficial properties to humans and how the composition of the microbiota may be manipulated for human health.

In addition to providing an understanding of the biology of these interactions, there are numerous translational aspects to these studies. By understanding the factors that contribute to compositional changes in this ecosystem, and how we can impact the composition of the microbiota, we will eventually be able to manipulate the bacterial community for better health outcomes, resilence to disease, and to more effectively intervene in intestinal dysbiosis. Designer "symbionts/probionts" might be used to deliver immunogenic molecules for vaccines, antimicrobial molecules targeting harmful bacteria such as Clostridium difficile, and for the delivery of other health promoting molecules.

Recent publications

  • Coyne M, Comstock L. 2019. Type VI secretion systems and the gut microbiota. Microbiol Spectrum 7(2):PSIB-0009-2018.
  • García-Bayona L, Comstock LE. 2018. Bacterial antagonism in host-associated microbial communities. Science 361.
  • McEneany VL, Coyne MJ, Chatzidaki-Livanis M, Comstock LE. 2018. Acquisition of MACPF domain-encoding genes is the main contributor to LPS glycan diversity in gut Bacteroides species. ISME J doi:10.1038/s41396-018-0244-4
  • Chatzidaki-Livanis M, Coyne MJ, Roelofs KG, Gentyala RR, Caldwell JM, Comstock LE. 2017. Gut symbiont Bacteroides fragilis secretes a eukaryotic-like ubiquitin protein that mediates intraspecies antagonism. mBio 8:e01902-01917.
  • Roelofs KG, Coyne MJ, Gentyala RR, Chatzidaki-Livanis M, Comstock LE. 2016. Bacteroidales secreted antimicrobial proteins target surface molecules necessary for gut colonization and mediate competition in vivo. mBio 7:e01055-01016.
  • Rakoff-Nahoum S, Foster KR, Comstock LE. 2016. The evolution of cooperation within the gut microbiota. Nature 533:255-259.
  • Coyne MJ, Comstock LE. 2016. A new pillar in pilus assembly. Cell 165:520-521.
  • Chatzidaki-Livanis M, Geva-Zatorsky N, Comstock LE. 2016. Bacteroides fragilis type VI secretion systems use novel effector and immunity proteins to antagonize human gut Bacteroidales species. Proc Natl Acad Sci USA 113:3627-3632.
  • Coyne MJ, Roelofs KG, Comstock LE. 2016. Type VI secretion systems of human gut Bacteroidales segregate into three genetic architectures, two of which are contained on mobile genetic elements. BMC Genomics 17:58.