Interaction with Gut Microbiota Plays a Causative Role in Grape Powder-Mediated Anti-Colitis Effects in Mice

Abstract

Abstract Objectives Gut microbiota is recognized to play a regulatory role in gut health and diseases. Previously, in a mouse model of colitis-associated colorectal cancer, we found that 10% grape powder (10GP) diet, which contains 0.033% polyphenols, attenuated colitis symptoms and restored colitis-changed gut microbial composition. However, it is not clear whether microbial modulation by 10GP directly contributes to the observed protective effects. To address the question, we compared the effect of 10GP on colitis in the presence and absence of antibiotics in mice. Methods Male Balb/c mice were gavaged with either water or antibiotic cocktail (ABX) daily for 7 days. For both water and ABX-treated mice, we further divided them into three subgroups: 1) healthy control (non-DSS), 2) mice fed with control diet and treated by 1.8% dextran sodium sulfate (DSS) in drinking water, and 3) mice fed with 10GP diet and treated with DSS (DSS-10GP). During the study, we monitored mice’ body weight and evaluated their colitis symptoms including stool consistency and rectal bleeding. All mice were sacrificed 9–10 days after DSS administration. Results Compared with conventional mice, ABX-treated mice had lowered liver and colon weight, increased level of fecal acetate and decreased levels of fecal butyrate and propionate. For both conventional and ABX-treated mice, DSS treatment caused colitis symptoms including rectal bleeding and diarrhea, colonic tissue damage, increased spleen weight and shortened colon length. Importantly, 10GP significantly alleviated DSS-induced colitis symptoms in non-ABX conventional mice, as indicated by attenuated fecal bleeding and diarrhea, reduced colonic tissue damage, and lowered spleen weight and colon weight to length ratio as inflammatory indexes. In contrast, these protective effects of 10GP were not observed in the ABX-treated mice. Conclusions 10GP diet showed protective effects against DSS-induced colitis in conventional mice, but not ABX-treated mice. This observation indicates that interaction between 10GP and gut microbiota plays a causative role in 10GP-mediated protective effects on colitis. Funding Sources California Table Grape Commission.