Background & Aims Diet has major effects on the intestinal microbiota, but the exact mechanisms that alter complex microbial communities have been difficult to elucidate. In addition to the direct influence that diet exerts on microbes, changes in microbiota composition and function can alter host functions such as gastrointestinal (GI) transit time, which in turn can further affect the microbiota. Methods We investigated the relationships among diet, GI motility, and the intestinal microbiota using mice that are germ-free (GF) or humanized (ex-GF mice colonized with human fecal microbiota). Results Analysis of gut motility revealed that humanized mice fed a standard polysaccharide-rich diet had faster GI transit and increased colonic contractility compared with GF mice. Humanized mice with faster transit due to administration of polyethylene glycol or a nonfermentable cellulose-based diet had similar changes in gut microbiota composition, indicating that diet can modify GI transit, which then affects the composition of the microbial community. However, altered transit in mice fed a diet of fermentable fructooligosaccharide indicates that diet can change gut microbial function, which can affect GI transit. Conclusions Based on studies in humanized mice, diet can affect GI transit through microbiota-dependent or microbiota-independent pathways, depending on the type of dietary change. The effect of the microbiota on transit largely depends on the amount and type (fermentable vs non-fermentable) of polysaccharides present in the diet. These results have implications for disorders that affect GI transit and gut microbial communities, including irritable bowel syndrome and inflammatory bowel disease.

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Alterations of gastrointestinal (GI) motor function are part of the visceral responses to stress. Inhibition of gastric emptying and stimulation of colonic motor function are the commonly encountered patterns induced by various stressors. Activation of brain corticotropin-releasing factor (CRF) receptors mediates stress-related inhibition of upper GI and stimulation of lower GI motor function through interaction with different CRF receptor subtypes. CRF subtype 1 receptors are involved in the colonic and anxiogenic responses to stress and may have clinical relevance in the comorbidity of anxiety/depression and irritable bowel syndrome.

1 The characterization of corticotropin releasing factor (CRF) and, more recently, the discovery of additional CRF-related ligands, urocortin 1, urocortin 2 and urocortin 3, the cloning of two distinct CRF receptor subtypes, 1 (CRF 1 ) and 2 (CRF 2 ), and the development of selective CRF receptor antagonists provided new insight to unravel the mechanisms of stress. Activation of brain CRF 1 receptor signaling pathways is implicated in stress-related endocrine response and the development of anxiety-like behaviors. 2 Compelling evidence in rodents showed also that both central and peripheral injection of CRF and urocortin 1 mimic acute stress-induced colonic response (stimulation of motility, transit, defecation, mucus and watery secretion, increased ionic permeability and occurrence of diarrhea) in rodents. Central CRF enhances colorectal distention-induced visceral pain in rats. Peripheral CRF reduced pain threshold to colonic distention and increased colonic motility in humans. 3 Nonselective CRF 1 /CRF 2 antagonists and selective CRF 1 antagonists inhibit exogenous (central or peripheral) CRF-and acute stress-induced activation of colonic myenteric neurons, stimulation of colonic motor function and visceral hyperalgesia while selective CRF 2 antagonists have no effect. None of the CRF antagonists influence basal or postprandial colonic function in nonstressed animals. 4 These findings implicate CRF 1 receptors in stress-related stimulation of colonic function and hypersensitivity to colorectal distention. Targeting CRF 1 -dependent pathways may have potential benefit against stress or anxiety-/depression-related functional bowel disorders.