A gut triumvirate rules homeostasis

Abstract

IgA regulates intestinal homeostasis by maintaining appropriate communities of bacteria within the gut. A new study shows that intestinal bacteria regulate metabolism via IgA (pages 1585–1593).

Figure 1

Intestinal bacteria regulate metabolism and immunity through an IgA-dependent mechanism. In healthy individuals (left), B cell–derived plasma cells release IgA onto the mucosal surface, where IgA binds to commensal bacteria. IgA-coated bacteria regulate intestinal immunity and homeostasis by delivering signals through microbial sensors on IECs. Shulzhenko et al. show that in addition to enhancing protection through immune pathways controlled by the cytokine interferon (IFN), these signals also regulate the intake of food lipids through metabolic pathways controlled by the transcription factor Gata4. In IgA-deficient individuals (right), IECs upregulate the expression of IFN-dependent genes to compensate for the lack of adaptive humoral immunity. This upregulation leads to a downregulation of the expression of genes regulated by Gata4. The resulting gene imbalance impairs the absorption of lipids, such as cholesterol, by IECs, resulting in metabolic disorders.