Interaction between IgA and gut microbiota and its role in controlling metabolic syndrome

Abstract

Summary Immunoglobulin A (IgA) is the most abundant immunoglobulin isotype secreted into the mucosal tissues, mainly intestinal mucus. Humans can produce several grams of IgA every day, accounting for three quarters of the body's total immunoglobulin content. IgA, together with mucus and antimicrobial peptides, forms the first line of defence for intestinal epithelial cells, protecting them from a significant number of intestinal antigens. IgA also plays a principal role in controlling the gut microbiota (GM), and disruption in IgA can result in dysbiosis, such as the enrichment of Proteobacteria, which are generally bound by IgA. Proteobacteria overexpansion is also usually seen in obesity and colitis. Consistent with this, IgA dysfunction frequently results in metabolic syndrome (MetS), including conditions such as obesity, adiposity, insulin resistance, and inflammation. In contrast, enhanced IgA function can improve, and even prevent, MetS. Interactions among IgA, GM, and metabolism provide a promising avenue to combat MetS.

IgA dysfunction induced by the early-lifetime disruption of gut microbiota aggravates diet–induced metabolic syndrome in mice

“…A similar trend was evident for the antigens from the feces of P mice compared to the LDP mice but did not reach signi cance (P = 0.094). Moreover, the mRNA expression of the Jchain and IL-6 of the ileum tissue was also higher, while tumor necrosis factor (ligand) superfamily, member 13 (also known as APRIL) and 13b (also known as BAFF) were not in uenced, when cultured with antigens derived from the feces of Ctr and F mice than those from the LDP mice (Figure 3B), suggesting that Ctr and F antigens may increase IgA production through enhancing the survival and activity of IgA+ PCs 19 .…”

“…Early-life high-dose antibiotic treatment has been shown to transiently inhibit the intestinal IgA response in mice [17][18] . As intestinal SIgA is closely related to the development of MetS 21 , we then sought to determine the in uence of early-life LDP on intestinal IgA response. There were no signi cant difference in the fecal SIgA among all 14 d and 21 d age of mice, suggesting that the passive SIgA received from their mothers via breast milk was not in uenced by LDP (Figure S2A).…”

“…Intestinal SIgA can bind to the microbial antigens, preventing bacterial encroachment and adhesion to intestinal epithelial cells (IECs) as well as the translocation of bacteria and their metabolites, such as lipopolysaccharides (LPS) and agellin, therefore protecting hosts from in ammation 19 . We then sought to investigate the in uences of LDP-induced reduction in intestinal SIgA on bacterial encroachment and in ammation in 25-week-old mice from Study 3.…”

“…It has been previously reported that transient high-dose antibiotics treatment during early life resulted in a relatively long-lasted (up to 70 d of age) reduction in fecal SIgA [17][18] , which is the most abundant immunoglobulin isotype in humans and mice and is a master controller of GM that has key role in regulating MetS 19 . However, the prolonged in uence of high-dose antibiotics on the intestinal SIgA and its correlation with metabolic disease was not determined [17][18] .…”

High-Fat Diet and Age-Dependent Effects of IgA-Bearing Cell Populations in the Small Intestinal Lamina Propria in Mice

“…It has been reported that promoting factors of IgA secretion are decreased in high-fat-diet (HFD)-fed mice [ 22 ]. Another paper suggested that IgA secretion may be inhibited in the context of low-grade inflammation and metabolic syndrome in obese humans and mice [ 23 ]. However, most reviews on diabetes and immunity do not discuss humoral immunity, including IgA responses [ 24 ].…”