Shaping of the gut microbiota by B lymphocytes influences GATA4-dependent lipid absorption and body fat accumulation (90.8)

Abstract

Abstract In order to understand the role for B lymphocytes in normal physiology of intestine, we compared global gene expression in the jejunum of wild-type (WT) and B-cell knockout (KO) mice. We found about 300 genes whose expression differed between WT and B-cell KO mice. Genes down-regulated in B- cell KO intestines, were highly enriched for lipid/energy metabolism genes. Consistent with this result, we found lower amounts of para-genital fat and serum leptin level in B-cell KO mice than in their B-cell-sufficient littermates. We revealed GATA4 as the most enriched transcription factor for the down regulated genes. Conditional KO of Gata4 in the intestinal epithelium showed a high correlation with BcKO gene signature. We also found a decrease in cholesterol absorption in the gut of B-cell KO mice (p<0.005) previously observed in Gata4 intestinal KO. In addition, Gata4 KO mice perfectly recapitulated the systemic effects observed in B-cell KO mice presenting decreased levels of body fat and leptin (p<0.01). Studying the mechanism, we found that mice that have B lymphocytes but do not produce soluble antibodies exhibit a very similar gene expression profile as the B-cell KO mice implying that this phenomenon is antibody-dependent. Under germ-free conditions, we found almost no difference between B-cell KO and control mice. Thus we conclude that B lymphocytes are involved in the control of GATA4-dependent lipid absorption and accumulation of body fat by shaping the gut microflora.