Genetic mutation on Escherichia coli genome during adaptation to the murine intestine is optimized to the host's diet.

The mammalian gut microbes colonize in the intestinal tract of their host and adapt to and establish the colonization of the intestinal environment. During adaptation to the mammalian intestine, genetic mutations of Escherichia coli, which is a prevalent species in the human gut, have been observed. However, the effect of diet change on the genetic mutation of E. coli remains unclear. Here, we show that mutations in sugar metabolism-related genes (gatC, araC, malI) are notably accumulated in the E. coli genome beyond host immunity during 3 months of the colonization. Besides, we experimentally confirmed that the deletion of several genes elevates the fitness of E. coli in the murine intestine and that the increased fitness of these mutations depended on host diet. The mechanism of these genes enhancing intestinal fitness was associated with unexpected metabolites, the abundance of which depends on the diet. Our study reveals one aspect of the intestinal adaptation mechanisms of microbiota and provides fundamental knowledge to control the microbiome.