Regulators of Gut Motility Revealed by a Gnotobiotic Model of Diet-Microbiome Interactions Related to Travel

Abstract

SUMMARY To understand how different diets, the consumers’ gut microbiota and the enteric nervous system (ENS) interact to regulate gut motility, we developed a gnotobiotic mouse model that mimics short-term dietary changes that happen when humans are traveling to places with different culinary traditions. Studying animals transplanted with the microbiota from humans representing each cuisine and fed a sequence of diets representing those of all donors, we find that correlations between bacterial species abundances and transit times are diet-dependent. However, the levels of unconjugated bile acids - reflecting microbial bile salt hydrolase activity - correlate with faster transit across diets, including a Bangladeshi diet. Mice harboring a consortium of sequenced bacterial strains from the Bangladeshi donor’s microbiota and fed a Bangladeshi diet revealed that the commonly used spice, turmeric, slows transit times. Turmeric affects gut motility via bacterial bile acid deconjugation and modulation of Ret signaling in the ENS. These results demonstrate how a single food ingredient interacts with a functional microbiota trait to regulate host physiology.

Ret receptor tyrosine kinase sustains proliferation and tissue maturation in intestinal epithelia

“…Whilst the contribution of enteric aganglionosis to HSCR is unquestionable, our findings raise the possibility that, if the epithelial expression of Ret is conserved in humans, dysregulation of epithelial signalling may contribute to disorders that, like HSCR, result from Ret mutation. Epithelial Ret signalling might also contribute to other aspects of gastrointestinal physiology previously shown to be affected by reduced Ret function, such as intestinal motility, gut–microbiota interactions and the compensatory response to massive small bowel resection (Gianino et al , 2003; Hitch et al , 2012; Dey et al , 2015). Interestingly, HSCR is typically diagnosed around birth due to defects in gastrointestinal functions.…”

Dual epithelial and immune cell function of Dvl1 regulates gut microbiota composition and intestinal homeostasis

“…Abnormalities in these constituents of the intestinal ecosystem regulate the microbiota composition, which in turn regulates GI motility. It was recently shown that the microbiota can regulate host physiology (57). Elimination of the microbiota caused dilatation of the cecum as a result of abnormal motility that returned to normal upon recolonization with bacteria (58), and it has been proposed that the mechanism underlying this involves regulation by the microbiota of Toll-like receptor expression in the intestine (59).…”

Gene-environment interactions and the enteric nervous system: Neural plasticity and Hirschsprung disease prevention

“…Strong support for microbial effects on the ENS comes from studies in germ free mice, since these animals have altered motility and changes in ENS structure including fewer myenteric neurons, an increased proportion of NO neurons, and fewer calbindin+ myenteric neurons compared to specific pathogen free or conventionally colonized animals (Collins et al, 2014; Dey et al, 2015; McVey Neufeld et al, 2015). The mechanisms underlying these observations are likely to be complicated.…”