Attenuating Dysbiosis with Diet, Resistant Starch and Microbiota Transplant.

Abstract

CD Obese prone (OP) and obese resistant (OR) rats (derived from Sprague Dawley rats) were used to study mitigation strategies for obesity and diet-induced dysbiosis (an imbalance in microbiota composition). Dysbiosis was induced using a high fat (HF) diet. Study 1 determined the effect of switching to a low fat (LF) diet or a LF diet supplemented with resistant starch (RS) on dysbiosis and metabolic parameters. Study 2 determined the effect of a microbiota transplant between OR and OP rats on dysbiosis and metabolic parameters. Prior to the transplant, the effectiveness of knocking down total bacteria in recipient rats by antibiotics and the bowel cleansing preparation MiraLAX® was tested. Dysbiosis was evaluated by determining the number of gene copies of targeted microbial groups. Correlations between microbiota composition and body weight and fat accretion were determined. The abundance of Clostridium butyricum was significantly higher in OR rats, was not affected by diet including RS and correlated negatively with body weight, fat accretion and inflammation in fat tissue. Abundance of the archaea Methanobrevibacter smithii was not affected by the obesity phenotype and was also not affected by a HF or LF diet but, was significantly increased by dietary RS in OP but not OR rats. In absence of obesity, M.smithi abundance did not change and fermentation levels changed only modestly. Increase of M. smithii and the resultant increased fermentation of RS in the presence of obesity was beneficial. It improved metabolic parameters in OP rats. Species from the genera Roseburia and Prevotella were not significantly affected by diet or obese phenotype. While knockdown of gut microbiota by antibiotics was effective, the microbiota transplant did not transmit the parameters of the donor phenotype between OP and OR rats. The results demonstrate that C. butyricum is part of the core microbiota that affects metabolic parameters and is not altered by diet. Methanobrevibacter smithii abundance depends on dietary components and significantly affects metabolic parameters in the obese phenotype.