Crohn'S Disease, Obesity, and High Crohn'S Disease Genetic Risk Are Associated with Parallel Changes in the Microbiome of the Cecal and Sigmoid Mucosal-Luminal Interface

pre-treated with antibiotics and polyethylene glycol (PEG) per established protocols and subsequently gavaged with a mixture of ∆ntrC and wild-type MP1 that have tetracyclineinduced fluorescent protein tags.Stool serial dilutions were performed and colony counts obtained weekly for calculation of competitive indices.Results: When cultured aerobically, ∆ntrC E. coli exhibited both a growth delay and reduction in growth yield that was more pronounced in LB medium.Anerobically, ∆ntrC showed a growth delay but reached a similar OD in stationary phase compared to wild-type MP1 in both M9 and LB media.Complementation of the ntrC deletion in trans restored wild-type growth.Surprisingly, despite a clear growth defect in vitro, oral co-inoculation of ∆ntrC MP1 with wild-type MP1 in mice resulted in higher engraftment of ∆ntrC MP1 compared to wild-type MP1 (~10 9 colony forming units -cfu versus 10 7 cfu) in the gastrointestinal tract.This 2-log competitive advantage for ∆ntrC MP1 over wild-type MP1, was sustained for a period of at least 1 month (p<0.01).Conclusions: Our results suggest that the murine gut provides a unique environment in which the lack of the NtrB/NtrC two-component system has a growth and/or engraftment advantage over the wild-type condition.This environment was not recapitulated in vitro since ∆ntrC MP1 showed a clear growth disadvantage in two growth media under both anaerobic and aerobic conditions.This ntrC response in vivo is unique since previous observations showed that disrupting the other 30 two-component signaling systems in the E coli genome did not lead to a growth advantage.This observation may have particular relevance to IBD where E. coli are an important component of the dysbiotic microbiota.