Resistant starch significantly alters gut microbiota and liver metabolome in mice fed a high fat diet (822.13)

Abstract

Resistant starch (RS) is a fermentable dietary fiber shown to alter gut hormones and modify the gut microbiome. Because RS impacts the gut microbiota, we hypothesize that RS changes gut‐derived signals reaching the liver by altering the gut microbiota and, in turn altering liver metabolism. To assess the effects of RS on the liver metabolome under obesogenic conditions, male C57Bl/6J mice were fed a 45% fat diet for 10 weeks supplemented with type 2 RS (10% by wt) or maltodextrin (n=15/group). As expected, increased cecal weights (by 55%, p<0.001) and significant changes in the cecal microbiome were observed. At the phylum level there was an increase in Bacteroidetes (by 53%, p<0.001) and decrease in Firmicutes (by 52%, p<0.001) in the RS‐fed group. Despite no differences in food intake, adiposity, liver weights and liver triglycerides, RS mice displayed markedly altered liver metabolites, in particular reduced liver amino acids (reduced 15‐52% for all measured amino acids except Gln), creatinine (by 40%, p<0.001) and urea (by 28%, p<0.001). These metabolites were equivalent in RS plasma vs. controls, suggesting that RS effects were due to changes specific to liver AA biochemistry or transport, and not simply due to lower blood AA. Reductions in these nitrogenous metabolites by RS may have implications in the dietary treatment of chronic kidney disease, and should provide important clues about gut‐derived signaling pathways that impact the liver.Grant Funding Source: Supported by: Danish Council for Strategic Research, USDA‐ARS Intramural Project 5306‐51530‐019‐00