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

• Published in: Neurogastroenterology and motility 2020-02, Vol.32 (2), p.e13745-n/a
• Main Authors: Beraldi, Evandro José, Borges, Stephanie Carvalho, Almeida, Fernanda Losi Alves, Santos, Andrey, Saad, Mario José Abdalla, Buttow, Nilza Cristina
• Format: Article
• Language: English
• Subjects: Animals; Calretinin; Colon; colonic microbiota; Cytokines; Diet, High-Fat - adverse effects; Dietary intake; diet‐induced obesity; Enteric nervous system; Gastrointestinal diseases; Gastrointestinal Microbiome; Gastrointestinal Motility - physiology; Gene expression; Glial cells; High fat diet; Immunofluorescence; Inflammation; Intestinal motility; Intestine; Inulin; Inulin - pharmacology; Male; Mice; Microbiota; Motility; myenteric plexus; Myenteric Plexus - pathology; Myosin; Neuronal-glial interactions; Neurons; Neurons - pathology; Nitric-oxide synthase; Obesity; Obesity - etiology; Obesity - pathology; Population studies; Probiotics; Probiotics - pharmacology; Vasoactive agents; Vasoactive intestinal peptide
• ISSN: 1350-1925; 1365-2982
• DOI: 10.1111/nmo.13745

Background 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. Methods Swiss mice were fed purified rodent diet or HFD (59% kcal fat), or both diets supplemented with inulin for 17 weeks. 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. Key Results 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. Conclusions and Inferences 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. A high‐fat diet causes neuronal loss and intestinal dysmotility in the colon of obese Swiss mice, without changes in the major groups of colonic microbiota. These findings reinforce that the lipotoxicity of the diet has a major role in the damage to the enteric nervous system.