Intestinal Dysbiosis Contributes to the Delayed Gastrointestinal Transit in High-Fat Diet Fed Mice

Mallappa Anitha, François Reichardt, Sahar Tabatabavakili, Behtash Ghazi Nezami, Benoit Chassaing, Simon Mwangi, Matam Vijay-Kumar, Andrew Gewirtz, Shanthi Srinivasan

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Abstract

Background & Aims: High-fat diet (HFD) feeding is associated with gastrointestinal motility disorders. We recently reported delayed colonic motility in mice fed a HFD for 11 weeks. In this study, we investigated the contributing role of gut microbiota in HFD-induced gut dysmotility. Methods: Male C57BL/6 mice were fed a HFD (60% kcal fat) or a regular/control diet (RD) (18% kcal fat) for 13 weeks. Serum and fecal endotoxin levels were measured, and relative amounts of specific gut bacteria in the feces were assessed by real-time polymerase chain reaction. Intestinal transit was measured by fluorescent-labeled marker and a bead expulsion test. Enteric neurons were assessed by immunostaining. Oligofructose (OFS) supplementation with RD or HFD for 5 weeks also was studied. In vitro studies were performed using primary enteric neurons and an enteric neuronal cell line. Results: HFD-fed mice had reduced numbers of enteric nitrergic neurons and showed delayed gastrointestinal transit compared with RD-fed mice. HFD-fed mice had higher fecal Firmicutes and Escherichia coli and lower Bacteroidetes compared with RD-fed mice. OFS supplementation protected against enteric nitrergic neuron loss in HFD-fed mice, and improved intestinal transit time. OFS supplementation resulted in a reduction in fecal Firmicutes and Escherichia coli and serum endotoxin levels. In vitro, palmitate activation of TLR4 induced enteric neuronal apoptosis in a Phospho-c-Jun N-terminal kinase-dependent pathway. This apoptosis was prevented by a c-Jun N-terminal kinase inhibitor and in neurons from TLR4-/- mice. Conclusions: Together our data suggest that intestinal dysbiosis in HFD-fed mice contribute to the delayed intestinal motility by inducing a TLR4-dependent neuronal loss. Manipulation of gut microbiota with OFS improved intestinal motility in HFD mice.

Original languageEnglish (US)
Pages (from-to)328-339
Number of pages12
JournalCMGH
Volume2
Issue number3
DOIs
StatePublished - May 1 2016

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All Science Journal Classification (ASJC) codes

  • Hepatology
  • Gastroenterology

Cite this

Anitha, M., Reichardt, F., Tabatabavakili, S., Nezami, B. G., Chassaing, B., Mwangi, S., Vijay-Kumar, M., Gewirtz, A., & Srinivasan, S. (2016). Intestinal Dysbiosis Contributes to the Delayed Gastrointestinal Transit in High-Fat Diet Fed Mice. CMGH, 2(3), 328-339. https://doi.org/10.1016/j.jcmgh.2015.12.008