T cell–mediated regulation of the microbiota protects against obesity

T cells help keep you lean The gut microbiota is a critical factor regulating mammalian metabolism. The host immune system, in turn, can shape the microbiome, in part via immunoglobulin A (IgA) antibodies. Petersen et al. report that mice defective in T follicular helper cell development and gut IgA production show hallmarks of metabolic syndrome with age (see the Perspective by Wang and Hooper). These mice gain more weight, accumulate more fat, and show greater insulin resistance compared with controls. IgA in these mice inappropriately targets Clostridia species and allows for the outgrowth of Desulfovibrio. Clostridia suppress and Desulfovibrio enhance host lipid absorption by modulating CD36 expression. A better understanding of the microbial products that modulate lipid absorption may open the door to future therapies for obesity and metabolic disease. Science , this issue p. eaat9351 ; see also p. 316