LAUSR

IgA influences bacterial fitness in the intestinal lumen and is only partially compensated for by IgM in selective IgA-deficient patients. IgA leads the way in the gut IgA is the most abundant mucosal antibody, and experiments with animal models suggest that it may enforce the gut barrier to prevent dangerous bacteria from damaging the host. However, humans deficient specifically in IgA often have only mild symptoms. Fadlallah et al. examined the fecal microbiomes of healthy individuals in comparison to those deficient in IgA. Overall bacterial diversity was comparable, but different genera were predominant in the patients. They investigated which bacteria were bound by different isotypes and concluded that IgM could partially compensate for the lack of IgA in patients, but not entirely. Their results suggest that, in humans, IgA is not solely responsible for controlling infections but does shape the microbiome. Paradoxically, loss of immunoglobulin A (IgA), one of the most abundant antibodies, does not irrevocably lead to severe infections in humans but rather is associated with relatively mild respiratory infections, atopy, and autoimmunity. IgA might therefore also play covert roles, not uniquely associated with control of pathogens. We show that human IgA deficiency is not associated with massive quantitative perturbations of gut microbial ecology. Metagenomic analysis highlights an expected pathobiont expansion but a less expected depletion in some typically beneficial symbionts. Gut colonization by species usually present in the oropharynx is also reminiscent of spatial microbiota disorganization. IgM only partially rescues IgA deficiency because not all typical IgA targets are efficiently bound by IgM in the intestinal lumen. Together, IgA appears to play a nonredundant role at the forefront of the immune/microbial interface, away from the intestinal barrier, ranging from pathobiont control and regulation of systemic inflammation to preservation of commensal diversity and community networks.