TY - JOUR
T1 - Complex interactions among diet, gastrointestinal transit, and gut microbiota in humanized mice
AU - Kashyap, Purna C.
AU - Marcobal, Angela
AU - Ursell, Luke K.
AU - Larauche, Muriel
AU - Duboc, Henri
AU - Earle, Kristen A.
AU - Sonnenburg, Erica D.
AU - Ferreyra, Jessica A.
AU - Higginbottom, Steven K.
AU - Million, Mulugeta
AU - Tache, Yvette
AU - Pasricha, Pankaj J.
AU - Knight, Rob
AU - Farrugia, Gianrico
AU - Sonnenburg, Justin L.
N1 - Funding Information:
Funding Supported by National Institutes of Health grant R01DK085025 (to J.L.S.), Digestive Diseases Center grant DK-41301 (Animal Models Core; to Y.T., M.M.) and K01 DK088937 (M.L.).
PY - 2013/5
Y1 - 2013/5
N2 - 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 nonfermentable) 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.
AB - 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 nonfermentable) 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.
KW - Dietary Carbohydrates
KW - Metabolomics
KW - Microbiome
KW - Serotonin
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U2 - 10.1053/j.gastro.2013.01.047
DO - 10.1053/j.gastro.2013.01.047
M3 - Article
C2 - 23380084
AN - SCOPUS:84876468494
SN - 0016-5085
VL - 144
SP - 967
EP - 977
JO - Gastroenterology
JF - Gastroenterology
IS - 5
ER -