Original ResearchFull Report: Basic and Translational—Alimentary TractComplex Interactions Among Diet, Gastrointestinal Transit, and Gut Microbiota in Humanized Mice
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.).