Preventive Effect of Spontaneous Physical Activity on the Gut-Adipose Tissue in a Mouse Model That Mimics Crohn’s Disease Susceptibility

Abstract

Crohn’s disease is characterized by abnormal ileal colonization by adherent-invasive E. coli (AIEC) and expansion of mesenteric adipose tissue. This study assessed the preventive effect of spontaneous physical activity (PA) on the gut-adipose tissue in a mouse model that mimics Crohn’s disease susceptibility. Thirty-five CEABAC10 male mice performed spontaneous PA (wheel group; n = 24) or not (controls; n = 11) for 12 weeks. At week 12, mice were orally challenged with the AIEC LF82 strain for 6 days. Body composition, glycaemic control, intestinal permeability, gut microbiota composition, and fecal short-chain fatty acids were assessed in both groups. Animals were fed a high fat/high sugar diet throughout the study. After exposure to AIEC, mesenteric adipose tissue weight was lower in the wheel group. Tight junction proteins expression increased with spontaneous PA, whereas systemic lipopolysaccharides were negatively correlated with the covered distance. Bifidobacterium and Lactobacillus decreased in controls, whereas Oscillospira and Ruminococcus increased in the wheel group. Fecal propionate and butyrate were also higher in the wheel group. In conclusion, spontaneous physical activity promotes healthy gut microbiota composition changes and increases short-chain fatty acids in CEABAC10 mice fed a Western diet and exposed to AIEC to mimic Crohn’s disease.

Role of Obesity, Mesenteric Adipose Tissue, and Adipokines in Inflammatory Bowel Diseases

“…In murine colitis models, the diet modifications are attributed to the alterations in the plasma levels of proinflammatory biomarkers and the expression of proinflammatory factors in VAT [102,108,128,[179][180][181][182][183][184][185][186][187]. It was demonstrated that the application of an HFD or HF/HSD diets and/or the development of obesity in mice increase(s) the intestinal permeability and bacterial translocation from the intestinal lumen to mesenteric fat, as well as profound changes in the microbiota [102,108,127,181,[184][185][186][187][188][189][190][191][192][193][194][195]. HFD or HF/HSD is also associated with significantly elevated LPS levels, the reduced expression of epithelial tight junction proteins, an increased macrophage infiltration, and the increased expression of proinflammatory biomarkers in the adipose tissue [102,127,181,[184][185][186][187][188][189][190][191][192][193][196]…”

“…It was demonstrated that the application of an HFD or HF/HSD diets and/or the development of obesity in mice increase(s) the intestinal permeability and bacterial translocation from the intestinal lumen to mesenteric fat, as well as profound changes in the microbiota [102,108,127,181,[184][185][186][187][188][189][190][191][192][193][194][195]. HFD or HF/HSD is also associated with significantly elevated LPS levels, the reduced expression of epithelial tight junction proteins, an increased macrophage infiltration, and the increased expression of proinflammatory biomarkers in the adipose tissue [102,127,181,[184][185][186][187][188][189][190][191][192][193][196][197][198]. Both, the Paneth cell area and the release of antimicrobial factors by Paneth cells are reduced in HFD-fed mice [197].…”

“…The hypothesis is moved forward that exercise may exert the protective effect, particularly in experimental colitis exacerbated by HFD. This beneficial effect of exercise is to some extent mediated via muscle-derived peptides, so-called "myokines" with endocrine effects, exerting a direct anti-inflammatory action, and/or specific effects on visceral fat [84,192,[223][224][225]. Liu et al [187] proposed an alternative explanation for the protective action of voluntary exercise in HFD-fed mice.…”

Intestinal Microbiota: A Novel Target to Improve Anti-Tumor Treatment?

“…The impact of PA on gut microbiota has not been widely studied in the literature. For instance, preclinical data showed that several weeks of running induced changes in the microbiota of rodents, depending on exercise modalities [159,160,161,162,163,164]. For example, in preliminary preclinical results of Maillard et al [159], spontaneous regular PA led to a significant decrease in mesenteric adipose tissue in a murine model, mimicking susceptibility to intestinal inflammation and associated with a change in beta diversity of the microbiota associated with the intestinal mucosa.…”

“…For instance, preclinical data showed that several weeks of running induced changes in the microbiota of rodents, depending on exercise modalities [159,160,161,162,163,164]. For example, in preliminary preclinical results of Maillard et al [159], spontaneous regular PA led to a significant decrease in mesenteric adipose tissue in a murine model, mimicking susceptibility to intestinal inflammation and associated with a change in beta diversity of the microbiota associated with the intestinal mucosa. In elite athletes, the levels of PA were correlated with gut microbial features (composition and functional microbial characteristics), including an increase of α-diversity, short-chain fatty acids production, and microbial metabolic capacity [165,166,167].…”