Host Phenotype Effects of Heritable Gut Microbiota

Overview

A link between the microbiome and host adiposity is well established in humans and mice; however, the components of the microbiome that underlie these effects have remained largely elusive. We have previously demonstrated that the highly heritable bacterial family Christensenellaceae is prevalent in the human gut microbiome and associated with a lean BMI (Goodrich et al 2014, Waters and Ley 2019). The goal of this research is to understand how members of the Christensenellaceae can impact host phenotype.

Projects

Christensenellaceae mediated reduction of host adiposity
The association of the Christensenellaceae with a healthy host phenotype is among the most robust associations of the microbiome with host phenotype to date (Waters and Ley, 2019). We have observed a direct relationship between the Christensenellaceae and body composition: in a gnotobiotic model that employed fecal transplants, the addition of C. minuta to donor stool was sufficient to blunt fat gain in the recipient. (Goodrich et.al., 2014). Here, we address the following outstanding questions:

  1. What are the molecular underpinnings of reduced fat gain?
  2. How does the addition of C. minuta remodel the gut community?
  3. What is the ecological function of C. minuta in the mammalian gastrointestinal tract?

Hydrogen based syntrophies of C. minuta with gut commensals
In vitro characterization of C. minuta revealed prolific hydrogen production, which supports the growth of M. smithii in the gut (Ruaud and Esquivel-Elizondo et al, 2020). We use in vitro and in vivo experiments to characterize the syntrophic interactions of C. minuta with key members of the microbiome.

 

Key Publications

Waters JL and Ley RE. The human gut bacteria Christensenellaceae are widespread, heritable, and associated with health. BMC Biology 17: 83 (2019)

Ruaud A, Esquivel-Elizondo S, de la Cuesta-Zuluaga J, Waters JL, Angenent LT, Youngblut ND and Ley RE. Syntrophy via interspecies H2 transfer between Christensenella and Methanobrevibacter underlies their global co-occurrence in the human gut. mBio 11 (1) e03235-19 (2020)

Goodrich JK, Waters JL, Poole AC, Sutter JL, Koren O, Blekhman R, Beaumont M, Van Treuren W, Knight R, Bell JT, Spector TD, Clark AG and Ley RE. Human genetics shape the gut microbiome. Cell 159: 789-799 (2014)