Colonic neuronal loss and delayed motility induced by high-fat diet occur independently of changes in the major groups of microbiota in Swiss mice.

Abstract

Obesity has been linked to gastrointestinal disorders, and the loss of myenteric neurons in the intestine caused by high-fat diets (HFD) has been attributed to changes in microbiota and lipotoxicity. We investigated whether the prebiotic inulin modulates bacterial populations and alleviates neuronal loss in mice fed HFD. Swiss mice were fed purified rodent diet or HFD (59% kcal fat), or both diets supplemented with inulin for 17weeks. Intestinal motility was assessed and a metagenome analysis of the colonic microbiota was performed. The gene expression of inflammatory markers was evaluated, and immunofluorescence was performed for different types of myenteric neurons and glial cells in the distal colon. The HFD caused obesity and delayed colonic motility. The loss of myenteric neurons and glial cells in obese mice affected all of the studied neuronal populations, including neurons positive for myosin-V, neuronal nitric oxide synthase, vasoactive intestinal peptide, and calretinin. Although obese mice supplemented with inulin exhibited improvements in colonic motility, neuronal, and glial cell loss persisted. The HFD did not altered the expression levels of inflammatory cytokines in the intestine or the prevalence of the major groups in microbiota, but inulin increased the proportion of the genus Akkermansia in the obese mice. In Swiss mice, the HFD-induced neuronal loss but did not change the major groups in microbiota. This suggests that, despite the increase in the beneficial bacteria, other factors that are directly linked to excess dietary lipid intake affect the enteric nervous system.