Select symbionts drive high IgA levels in the mouse intestine

Immunoglobulin A (IgA) is an important factor in maintaining homeostasis at mucosal surfaces, yet luminal IgA levels vary widely. Total IgA levels are thought to be driven by individual immune responses to specific microbes. Here, we found that the prebiotic, pectin oligosaccharide (pec-oligo), induced high IgA levels in the small intestine in a T cell-dependent manner. Surprisingly, this IgA-high phenotype was retained after cessation of pec-oligo treatment, and microbiome transmission either horizontally or vertically was sufficient to retain high IgA levels in the absence of pec-oligo. Interestingly, the bacterial taxa enriched in the overall pec-oligo bacterial community differed from IgA-coated microbes in this same community. Rather, a group of ethanol-resistant microbes, highly enriched for Lachnospiraceae bacterium A2, drove the IgA-high phenotype. These findings support a model of intestinal adaptive immunity in which a limited number of microbes can promote durable changes in IgA directed to many symbionts. [Display omitted] •A pectin-derived prebiotic creates an IgA-high phenotype in mice•The pec-oligo-reshaped microbial community dominantly transmits the IgA-high phenotype•The IgA-high phenotype is driven primarily by CD4+ T cells in the small intestine•Lachnospiraceae bacterium A2 is enriched in IgA-high mice and likely drives high IgA Zhang et al. demonstrate that long-term dietary intervention with pectin-derived oligosaccharides promotes the ability of specific bacteria, such as Lachnospiraceae bacterium A2, to elevate intestinal IgA that is directed against an array of symbionts. This activity could fit the definition of a keystone species that determines intestinal IgA levels.