ANTIMICROBIAL REMODELING OF GUT MICROBIOTA DIFFERENTIALLY AFFECTS BILE ACID PROFILE, SIGNALING AND ENTEROPROTECTIVE RESPONSE IN THE ILEUM AND COLON OF PIGS

An expanding body of evidence links the use of antimicrobials (ANT) in animal agriculture to the worldwide spread of antibiotic-resistant bacteria. It is urgent therefore to discontinue the non-therapeutic use of ANT in food-producing animals, but this undertaking is hampered by the still-elusive mechanism that mediates their growth-enhancing action. Available evidence supports the hypothesis that alterations in bile acid (BA) metabolism and signalling represent a conceivable mechanism for such ANT action. To investigate this proposition, 24 piglets were weaned at 21 days of age and fed diets supplemented (ANT) or not (control) with amoxicillin (300 ppm), colistin sulfate (120 ppm), and zinc oxide (2500 ppm). After 35 days, animals were sacrificed and samples of target tissues were collected for later analyses. Feeding ANT enhanced weight gain (P < 0.05) and altered (P < 0.01) colonic microbial diversity and functions mainly by suppressing bacteria of the genus Lactobacillus (P < 0.0001) and Clostridium (P < 0.02). This was associated with reduced bile salt hydrolase activity (P < 0.004) but increased BA dehydrozylating capacity (P < 0.008) in colonic content of ANT-fed pigs. In ileal mucosa ANT elevated (P < 0.03) the proportion of chenodeoxycholic (CDCA) and lithocholic (LCA) acids, whereas in colonic mucosa reduced (P < 0.03) the percentage of hyocholic acid (HCA) and increased (P < 0.04) the concentration of LCA, 6-oxo-LCA, deoxycholic acid (DCA), and the ratios hyodeoxycholic acid (HDCA)/HCA, LCA/HDCA, and LCA/CDCA. These alterations were paralleled by enhanced FXR signalling in both intestinal sections; however, related changes in the expression of genes and proteins involved in gut protection against bacteria, toxins, and inflammation were more pronounced in colonic mucosa. This work identifies BA as integrators of the host immune-inflammatory responses to ANT-mediated alterations in gut microbiota, making them a promising target for the development of alternatives to ANT. tech.service@fad.com, jose.pastor@lucta.com