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Morrison, Martine C; Gart, Eveline; Duyvenvoorde, Wim van; Snabel, Jessica; Nielsen, Mette Juul; Leeming, Diana Julie; Menke, Aswin; Kleemann, Robert
International journal of molecular sciences, 02/2022, Letnik: 23, Številka: 4Journal Article
The development of non-alcoholic steatohepatitis (NASH) has been associated with alterations in gut microbiota composition and reduced gut barrier function. is a gut microbe that is thought to have health-promoting properties, including the ability to improve gut barrier function and host metabolism, both when administered live and after heat-inactivation. We questioned whether heat-inactivated may reduce NASH development. Ldlr-/-.Leiden mice, a translational, diet-induced model for NASH, were fed a NASH-inducing high-fat diet (HFD) supplemented with heat-inactivated . After 28 weeks, effects of the treatment on obesity and associated metabolic dysfunction in the gut (microbiota composition and permeability), adipose tissue, and liver were studied relative to an untreated HFD control. Treatment with heat-inactivated did not affect body weight or adiposity and had no effect on plasma lipids, blood glucose, or plasma insulin. Heat-inactivated had some minor effects on mucosal microbiota composition in ileum and colon and improved gut barrier function, as assessed by an in vivo functional gut permeability test. Epidydimal white adipose tissue (WAT) hypertrophy and inflammation were not affected, but heat-inactivated did reduce hypertrophy in the mesenteric WAT which is in close proximity to the intestine. Heat-inactivated did not affect the development of NASH or associated fibrosis in the liver and did not affect circulating bile acids or markers of liver fibrosis, but did reduce PRO-C4, a type IV collagen synthesis marker, which may be associated with gut integrity. In conclusion, despite beneficial effects in the gut and mesenteric adipose tissue, heat-inactivated did not affect the development of NASH and fibrosis in a chronic disease setting that mimics clinically relevant disease stages.
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