The
secretory immunoglobulin A (
SIgA) in mammalian gut protects the organism from
infections and contributes to host physiology by shaping microbiota composition. The mechanisms regulating the adaptive
SIgA response towards gut microbes are poorly defined. Deletion of P2rx7, encoding for the
ATP-gated ionotropic
P2X7 receptor, leads to T follicular helper (Tfh) cells expansion in the Peyer's patches (PPs) of the small intestine, enhanced germinal centre (GC) reaction and
IgA secretion; the resulting alterations of the gut microbiota in turn affects host metabolism. Here, we define gut microbiota modifications that correlate with deregulated
SIgA secretion and metabolic alterations in P2rx7-/- mice. In particular, Lactobacillus shows enhanced
SIgA coating in P2rx7-/- with respect to wild-type (WT) mice. The abundance of
SIgA-coated lactobacilli positively correlates with Tfh cells number and
body weight, suggesting Lactobacillus-specific
SIgA response conditions host metabolism. Accordingly,
oral administration of intestinal Lactobacillus isolates from P2rx7-/- mice to WT animals results in altered
glucose homeostasis and fat deposition. Thus, enhanced
SIgA production by P2X7 insufficiency promotes Lactobacillus colonization that interferes with systemic metabolic homeostasis. These data indicate that
P2X7 receptor-mediated regulation of commensals coating by
SIgA is important in tuning the selection of bacterial taxa, which condition host metabolism.