Gastroenterology

Gastroenterology

Volume 144, Issue 5, May 2013, Pages 967-977
Gastroenterology

Original Research
Full Report: Basic and Translational—Alimentary Tract
Complex Interactions Among Diet, Gastrointestinal Transit, and Gut Microbiota in Humanized Mice

https://doi.org/10.1053/j.gastro.2013.01.047Get rights and content

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.

Section snippets

Animals

All animal experiments were in accordance with A-PLAC, the Stanford Institutional Animal Care and Use Committee, as described in Supplementary Materials and Methods. Diets are described in Supplementary Table 1.

Pyrosequencing/Data Analysis

Fecal DNA samples were sequenced at Duke Institute for Genome Sciences & Policy, and data were processed using QIIME 1.4.0.19

GI Transit Time

Whole gut transit time was determined using the carmine red method as previously described.20

Colonic Contractility Recording

Intracolonic pressure recording of the descending colon in conscious

Colonization of GF Mice With Human Microbiota Decreases GI Transit Time

GF mice were humanized by colonization with feces obtained from a single anonymous healthy human donor. Mice were used 4 to 8 weeks after humanization, which is a sufficient interval for the microbial community to stabilize.23 We first examined whether GI transit time was influenced by the presence of a complex intestinal microbiota when mice were fed a standard polysaccharide-rich diet. GI transit time was significantly shorter in humanized mice than GF controls (285 ± 18 vs 457 ± 13 minutes;

Discussion

Variation in GI transit time is commonly seen in healthy human subjects and also results from disease states including GI infections with rotavirus, cholera or Clostridium difficile colitis, inflammatory bowel disease, microscopic colitis, and IBS with constipation or diarrhea. Alterations in the microbiota have been described in several of these disease states and have often been implicated in their pathogenesis.10 This study illuminates the complex interactions among diet, GI transit, and gut

Conclusions

Based on the data presented here, we propose the following model for the interactions between diet, gut microbiota, and GI transit time in the host. GI transit time and gut microbiota are interrelated (Appendix panel A). Diet can independently affect both GI transit time and gut microbial composition and function (as determined by metabolite profiles). However, diet-induced changes in microbial composition may be mediated in part by changes in GI transit time (Appendix panel B), and the effect

Acknowledgments

The authors thank Peter Strege for help with preparation of figures and Sara Fisher for administrative help.

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    Conflicts of interest The authors disclose no conflicts.

    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.).

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