Purna C. Kashyap
Gastrointestinal (GI) motility enables mixing, storage, anterograde propulsion and absorption of nutrients, and represents one of the most important functions of the GI tract. GI transit time, the time for a food bolus to pass through the GI tract, is often used as a surrogate for GI motility. This seemingly simple process requires coordination among several key cell types in the enteric neuromuscular apparatus, including the enteric neurons and glia, interstitial cells of Cajal (ICC), smooth muscle, and immune cells. Until recently, the majority of the work on GI motility dis- orders has focused on the interplay among different host cell types, even though it is established that gut bacteria and luminal compounds have a significant impact on GI motility. However, recent studies have started to uncover this additional layer of complexity, exploring how gut microbiota and their products influence host GI physiology.
Studies of gut microbiota and neuro-muscular apparatus, including neuro-transmitters in the context of GI motility, have shown that gut microbiota and their products have effects on the enteric neurons, enteric muscularis macrophages, and enteric glia. Gut microbiota-derived lipopolysaccharide (LPS) improves enteric neuronal survival and influences GI motility (Figure 1), acting via the TLR4 and NF-kB pathway (Anitha et al., 2012). Gut microbiota products also influence the crosstalk between enteric neurons and muscularis macrophages (Figure 1), which plays an important role in maintain- ing normal GI motility (Muller et al., 2014). Serotonin, an important neurotransmitter in the gut that plays a role in modulating GI motility, can be modulated by gut microbes (Reigstad et al., 2015). Metabolites resulting from primary and secondary fermentation of dietary nutrients by gut microbes, such as short-chain fatty acids and bile acids (Figure 1), can increase serotonin biosynthesis and release in the gut, thereby altering GI motility in a diet- dependent manner (Kashyap et al., 2013).
The new study by Dey et al. (2015) provides an in-depth investigation of the interaction between diet and gut microbiota to elucidate the mechanisms by which these interactions influence GI motility. Travelers’ diarrhea is common during travel to the developing world and is often attributed to acquisition of pathogenic bacteria or viruses. However, an additional aspect of travel is short-term exposure to new diets. Diet is a dominant factor in shaping gut microbial communities (Wu et al., 2011) and has been shown to influence GI motility in both a microbiota-dependent and independent manner (Kashyap et al., 2013). In a series of elegant experiments, the authors subject gnotobiotic mice, colonized with microbiota from healthy human donors (humanized) from across the world, to multiple cycles of short-term dietary interventions, representing native and non-native diets. The authors were able to identify several bacterial taxa present in different groups of humanized mice that have diet-dependent effects on GI transit. Some of these taxa (e.g., E. desmolans) had opposite correlations with transit time depending on supplementation with native or non-native diet. As expected, diet also showed effects on gut microbiota that did not correlate with GI transit time.