A trilogue in the gut

A critical three-way conversation in the gut between B immune cells, the resident bacteria, and the intestinal epithelial lining maintains normal immunity and metabolism, according to research published this week in Nature Medicine. These results may explain the poor absorption of fat and therefore low weight gain that is often observed in immunodeficient patients, while also suggesting a new therapy. The mammalian gut consists of intestinal epithelia cells that absorb nutrients from the diet while blocking bacterial invasion, local immune cells, and resident bacteria. Polly Matzinger and her colleagues found that normally B cells release IgA antibodies to maintain a proper repertoire of the microbiota and routine function of the gut epithelium. However, when they created mice without B cells, or prevented the B cells from expressing IgA, the intestinal epithelial cells were induced by the microbiota to take a more active role in their own defense. This switch in behavior, however, comes at the expense of reduced expression of genes in the epithelial cells important for proper absorption of fats from the diet. These results may account for the unexplained gastrointestinal defects observed in immunodeficient patients, and the authors report data from such patients that are concordant with their mouse data. Their results also suggest that IgA treatment could be beneficial for this aspect of their condition.