Anti-REG3G monoclonal antibody, clone CBSB234CB.

Putative genetic markers have been associated with ETEC F4 (Mucine 4 [MUC4]; MUC4(GG;CG) as susceptible; MUC4A (c) as resistant) and F18 (Fucosyltransferase 1 [FUT1]; FUT1(GG;AG) as susceptible; FUT1(AA) as resistant) resistances respectively. In this study, 71 post-weaning pigs were followed from d0 (35 days old) to d42 (77 days of age) to investigate the effect of MUC4 or FUT1 genotypes on the mid-jejunal microbiota composition, pigs expression of genes related to inflammation (IL8, GPX2, REG3G, TFF3, CCL20 and LBPI) and glycomic binding pattern profile (Ulex europaeus agglutinin I [UEA] fucose-binding lectin and peanut agglutinin [PNA] galactose-specific), and on blood plasma targeted metabolomics profile, faecal score and performance parameters of growing healthy pigs. The MUC4 and FUT1 resistant genotypes improved the pigs' growth performance and had firmed faecal score susceptible genotypes in d0-d21 period. Pigs with MUC4(GG) genotype had a higher jejunal expression of genes relate to immune function (CCL20 and REG3G) than MUC4(CG) and MUC4A (c) pigs (p 0.05). MUC4(CG) pigs had higher expression of TFF3 (implicated in mucosal integrity) than MUC4(GG) and MUC4A (c) (p < 0.05). FUT1 influenced the alpha- and beta-jejunal microbial indices. The FUT1(AA) group had a higher number of operational taxonomic units (OTUs) belonging to Lactobacillus genus, while FUT1(GG) group had a higher number of OTUs belonging to Veillonella genus. MUC4A (c) pigs had lower scores for UEA on brush borders and goblet cells in villi than MUC4(GG) (p < 0.05). FUT1(AA) pigs had lower UEA positivity and higher PNA positivity on brush borders and goblet cells than FUT1(AG) and FUT1(GG) (p < 0.05). Both FUT1 and MUC4 influenced the metabolic profile of healthy pigs. Results highlight the role of MUC4 and FUT1 on pig intestinal homoeostasis and improved the knowledge regarding the potential interaction between host genetics, gut microbiota composition and host metabolism in a healthy status.

C-type regenerating islet derived-3 (Reg3) lectins defend against pathogens and keep commensal bacteria at a distance. Deficiency of Reg3g and Reg3b facilitates alcohol-induced bacterial translocation and alcoholic liver disease. Intestinal Reg3g is down-regulated in animal models of diet-induced obesity, but the functional consequences for nonalcoholic steatohepatitis (NASH) are unknown. The aim of this study was to investigate the role of Reg3 lectins in NASH. NASH was induced by a Western-style fast-food diet in mice deficient for Reg3g or Reg3b and in transgenic mice overexpressing Reg3g in intestinal epithelial cells (Reg3gTg). Glucose tolerance was assessed after 18 weeks and insulin resistance after 19 weeks of feeding. After 20 weeks, mice were assessed for features of the metabolic syndrome. Obesity was not different in genetically modified mice compared with their respective wild-type littermates. Glucose intolerance, liver injury, hepatic inflammation, steatosis, fibrosis, and bacterial translocation to mesenteric lymph nodes and to the liver were not different in Reg3g-deficient mice compared with wild-type littermates. Plasma endotoxin levels were higher in Reg3g-deficient mice. Reg3b deficiency protected against glucose intolerance, but liver disease, bacterial translocation, and plasma endotoxin levels were similar to wild-type littermates. Absence of either REG3G or REG3B protein in the ileum was not compensated for by up-regulation of the respective other REG3 protein. Transgenic Reg3g mice also developed liver injury, steatosis, and fibrosis similar to their wild-type littermates. Conclusion: In contrast to alcoholic liver disease, loss of intestinal Reg3 lectins is not sufficient to aggravate diet-induced obesity and NASH. This supports a multi-hit pathogenesis in NASH. Only glucose metabolism is affected by Reg3b deficiency.