ENTERAL BILE ACIDS MODULATE INTESTINAL IMMUNE RESPONSE AND GUT MICROBIOTA IN EARLY-WEANED PIGLETS CHALLENGED WITH LPS

Bile acids (BA) have recently emerged as regulators of intestinal immune homeostasis and mucosal integrity. We examined the effects of administering enterally deoxycholic acid (DCA) to early-weaned pigs challenged with lipopolysaccharide (LPS) on gut BA profile, immune response and microbiota. Twenty-four piglets were weaned at 21 d, acclimatized for 14 d, and subsequently grouped (n = 8) to be intragastrically infused with either deionized water (C+, C−) or 15 mg of DCA·kg−1 initial BW (DCA) daily during 14 d. On d 28, C+ and DCA piglets were injected i.p. with 150 µg LPS·kg−1 BW. Three h later, all animals were bled and killed for organ measurement and sampling. Blood samples were analyzed for endotoxin (EDT), interleukin (IL)-6, and tumor necrosis factor α (TNF-α). Expression of occludin, IL-6 and IL-10 genes and the concentration of individual BA were measured in the ileal mucosa. Colonic microbiota was characterized by sequencing bacterial 16S ribosomal-RNA. Individual BW and feed intake were recorded weekly. Data were analyzed with a mixed-effects model in which pig was treated as random effect and treatment as fixed effect. Compared with C-, LPS decreased total BA concentration (P < 0.01) and increased plasma TNF-α (P < 0.01) and EDT (P < 0.02) as well as hepatic (P < 0.01) and intestinal (P < 0.03) weight. Interestingly, DCA infusion increased the proportion of BA with the greatest ability to induce BA-signaling pathways (P < 0.05), prevented alterations (P > 0.10) in plasma EDT and intestinal weight, decreased expression of IL genes (P < 0.04) in the ileum, and enhanced (P < 0.05) feed intake. In addition, treating pigs with DCA increased (P < 0.05) Peptostreptococcaceae and Clostridiaceae whereas decreased (P < 0.05) Lactobacillaceae in the colon. In conclusion, DCA acted locally to prevent LPS-induced inflammation and barrier disruption of the intestinal mucosa. These effects were associated with changes in the intestinal BA signature. tech.service@fad.com