Genetic mutation in Escherichia coli genome during adaptation to the murine intestine is optimized for the host diet

Shinji Fukuda^1-4

(1) Institute for Advanced Biosciences, Keio University, Tsuruoka, Japan

(2) Transborder Medical Research Center, Faculty of Medicine, University of Tsukuba, Tsukuba, Japan

(3) Kanagawa Institute of Industrial Science and Technology, Kawasaki, Japan

(4) Laboratory for Regenerative Microbiology, Juntendo University Graduate School of Medicine, Tokyo, Japan.

Email: sfukuda@sfc.keio.ac.jp

Abstract

Mammalian gut microbes colonize the intestinal tract of their host and adapt to establish a microbial ecosystem. The host diet changes the nutrient profile of the intestine and has a high impact on microbiota composition. Genetic mutations in Escherichia coli, a prevalent species in the human gut, allow for adaptation to the mammalian intestine, as reported in previous studies. However, the extent of intestinal fitness elevated by genetic mutation and the effects of diet change on these mutations in E. coli remain unclear. Here, we show that notable mutations in sugar metabolism-related genes (gatC, araC, and malI) were detected in the E. coli genome just two weeks after colonization. Deletion of these genes elevated E. coli fitness in the murine intestine, though the extent was dependent on the host diet. In vitro cultures of medium containing nutrients abundant in the intestine also showed increased E. coli fitness after deletion of the genes-of-interest associated with their metabolism. Furthermore, the host diet was found to influence the developmental trajectory of gene mutations in E. coli. Taken together, we suggest that genetic mutations in E. coli are selected in response to the intestinal environment, which facilitates efficient utilization of nutrients abundant in the intestine. Our study reveals some of the intestinal adaptation mechanisms of gut microbes as well as a potential means by which we can manipulate the microbiota.