A Mediterranean-like fat blend protects against the development of severe colitis in the mucin-2 deficient murine model

Gut Microbes. 2022 Jan-Dec;14(1):2055441. doi: 10.1080/19490976.2022.2055441.

Abstract

There is a growing appreciation that the interaction between diet, the gut microbiota and the immune system contribute to the development and progression of inflammatory bowel disease (IBD). A mounting body of scientific evidence suggests that high-fat diets exacerbate IBD; however, there is a lack of information on how specific types of fat impact colitis. The Mediterranean diet (MD) is considered a health-promoting diet containing approximately 40% total fat. It is not known if the blend of fats found in the MD contributes to its beneficial protective effects.

Mice deficient in the mucin 2 gene (Muc 2-/-) were weaned to 40% fat, isocaloric, isonitrogenous diets. We compared the MD fat blend (high monounsaturated, 2:1 n-6:n-3 polyunsaturated and moderate saturated fat) to diets composed of corn oil (CO, n-6 polyunsaturated-rich), olive oil (monounsaturated-rich) or milk fat (MF, saturated-rich) on spontaneous colitis development in Muc2-/- mice. The MD resulted in lower clinical and histopathological scores and induced tolerogenic CD103+ CD11b+ dendritic, Th22 and IL-17+ IL-22+ cells necessary for intestinal barrier repair. The MD was associated with beneficial microbes and associated with higher cecal acetic acid levels negatively correlated with colitogenic microbes like Akkermansia muciniphila. In contrast, CO showed a higher prevalence of mucin-degraders including A. muciniphila and Enterobacteriaceae, which have been associated with colitis.

A dietary blend of fats mimicking the MD, reduces disease activity, inflammation-related biomarkers and improves metabolic parameters in the Muc2-/- mouse model. Our findings suggest that the MD fat blend could be incorporated into a maintenance diet for colitis.

Keywords: Colitis; bacteriome; diet; dietary fat; inflammation; mediterranean diet; mucin 2; nutrition; ulcerative colitis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Colitis* / chemically induced
  • Colitis* / prevention & control
  • Diet, High-Fat / adverse effects
  • Disease Models, Animal
  • Gastrointestinal Microbiome*
  • Inflammatory Bowel Diseases*
  • Mice
  • Mice, Inbred C57BL
  • Mucin-2 / genetics

Substances

  • Mucin-2

Grants and funding

NH was funded by a Canadian Institutes of Health Research - Frederick Banting and Charles Best Canada Graduate Doctoral Award and a Canadian Association of Gastroenterology PhD Studentship Award. This study was supported by a Crohn’s and Colitis Canada Grant-in-Aid to DLG and an NSERC Grant-in-Aid to SG; Natural Sciences and Engineering Research Council of Canada ; Crohn’s and Colitis Canada [Grant-in- Aid].