Bile acids supplementation improves colonic mucosal barrier via alteration of bile acids metabolism and gut microbiota composition in goats with subacute ruminal acidosis (SARA)

Subacute ruminal acidosis (SARA) is a common metabolic disease due to feeding high-concentrate (HC) diets to ruminants, especially dairy cows, in intensive farming system. Long term feeding HC diets commonly induce damages to hindgut barrier, leading to the translocation of harmful substances such as endotoxins (LPS) from lumen to blood, which results in a low-grade inflammation and stress response. Secondary bile acids (SBAs) play an important role in maintaining intestinal homeostasis. However, the function of SBAs on the intestinal epithelial barrier in SARA remains unclear. In this study, 15 growing goats were randomly divided into 3 groups, control group (30 % concentrate of dry matter, CON), SARA group (70 % concentrate of dry matter, SARA), and SARA+BAs group (70 % concentrate of dry matte, supplemented with 3 g/d/goat of BAs, SARA+BAs). The changes of mucosal permeability, gut microbiota and bile acids (BAs) profile was measured in the colon. The results showed that compared to CON group, the level of plasma D-lactate and diamine oxidase activity (DAO) (P <0.05) was elevated in SARA group, while BAs supplementation significantly decreased plasma DAO (P < 0.05). The thickness of colonic mucosa, goblet cells (GCs) number (P < 0.01) and the abundance of MUC2 and occludin expression (P < 0.05) were significantly decreased in SARA group, while BAs supplementation markedly increased GCs number and improved mucosal barrier. BAs effectively reduced the content of LPS and volatile fatty acids (VFAs) in the colonic digesta (P < 0.05). Furthermore, BAs ameliorated SARA-induced reduction of total BAs (P < 0.001), primary BAs (P < 0.05), and conjugated BAs (P < 0.05) including taurocholic acid (TCA), taurochenodeoxycholic acid (TCDCA) and taurodeoxycholic acid (TDCA), as well as significantly increased hyodeoxycholic acid (HDCA) and lithocholic acid (LCA) contents in colonic digesta. 16S rRNA gene sequence analysis revealed that BAs decreased the abundance of Prevotella and Treponema, but increased the abundance of Akkermansia which was positively correlated with GCs number and MUC2 abundance. BAs supplementation improved the changes in the abundance of Roseburia, Negativibacillus, Lactobacillus, and unclassified_f_prevotellaceae, which were correlated with TCA, TCDCA, and TDCA levels. RNA-Seq results showed that, compared to SARA group, BAs activated the PPAR signaling pathway which was positively correlated with the number of GCs. In summary, BAs supplementation remodels the profiles of gut microbiota and metabolites, activates the PPAR signaling pathway, and eventually ameliorates intestinal mucosal barrier damage.