1 research outputs found
Intestinal Dysbiosis Contributes to the Delayed Gastrointestinal Transit in High-Fat Diet Fed MiceSummary
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 Phosphoâc-Jun N-terminal kinaseâdependent 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. Keywords: Myenteric Neurons, Palmitate, Gut Microbiota, LPS, TLR4, Colon Transi