IgA dysfunctions induced by the early-lifetime disruption of gut microbitoa result in metabolic syndrome in mice

Abstract Backgroud: Disruption of the gut microbiota (GM), mainly induced by antibiotic treatments and C-sections, is prevalent during the early lifetime, which can result in lifelong changes in the GM composition and metabolism.Results: The GM of newborn mice was influenced after being subjected to transitory treatment with low-dose penicillin (LDP), resulting in a permanent reduction of intestinal IgA. Germ-free (GF) mice transferred GM from the LDP-treated mice also showed decreased intestinal IgA levels. Similarly, antigens derived from the LDP-treated mice induced lower IgA production during in vitro incubation with small intestinal tissues. Furthermore, a lack of intestinal IgA led to the persistent dysbiosis of mucosal GM, causing metabolic syndrome (MetS) in the LDP-treated mice. The mice lacking intestinal IgA (Pigr-/-) only showed transient alteration in GM after LDP exposure while the long-period metabolism was not influenced. Moreover, gavage with GM from the LDP-free mice or probiotics (partially) restored the GM and intestinal IgA, while improving the MetS in LDP-treated mice.Conclusions: The antibiotics–induced changes of GM in early lifetime permanently dampened the IgA responses to the GM, which lead to the long-term dysbiosis of intestinal mucosal bacteria and MetS.