Immunoglobulin A (IgA) is a major antibody in the gut. We previously observed that a high-fat diet (HFD) reduces IgA reactivity to gut microbiota, but the physiological implications have yet to be elucidated. We hypothesized that a reduction of IgA reactivity to gut microbiota induced by a HFD may contribute to development of gut dysbiosis and inflammation that accompanies HFD feeding. To test our hypothesis, we used Aicda deficient mice, which have a deficiency in IgA production. Aicda deficient mice and wild-type mice were fed normal-fat diet or HFD for 12 weeks. We found that HFD feeding but not Aicda deficiency altered the fecal microbiota composition. Meanwhile, Aicda deficiency significantly increased gene expression of inflammatory cytokines in the ileum, but not in the colon despite no significant difference between diets. These results suggest that a reduction of IgA reactivity to gut microbiota induced by HFD partly contributes to development of inflammation in the ileum, but not to gut dysbiosis. We also found that the fasting blood insulin level was significantly increased by Aicda deficiency only under HFD feeding. Furthermore, the gene expression of monocyte chemoattractant protein1, a major chemokine responsible for the onset of hyperinsulinemia, in the liver was significantly increased by HFD feeding and tended to be increased by Aicda deficiency. These findings suggest that a reduction of IgA reactivity to gut microbiota induced by HFD contributes to hyperinsulinemia partly via increasing monocyte chemoattractant protein-1 expression in the liver.

免疫球蛋白 A (IgA) 是肠道中的主要抗体。我们之前观察到高脂饮食 (HFD) 会降低 IgA 对肠道微生物群的反应性，但其生理意义尚未阐明。我们假设 HFD 诱导的 IgA 对肠道微生物群的反应性降低可能会导致伴随 HFD 喂养的肠道菌群失调和炎症的发展。为了检验我们的假设，我们使用了缺乏 IgA 的Aicda缺陷小鼠。Aicda缺陷小鼠和野生型小鼠被喂食正常脂肪饮食或HFD 12 周。我们发现 HFD 喂养而不是Aicda缺乏改变了粪便微生物群的组成。与此同时，爱达缺乏显着增加了回肠中炎性细胞因子的基因表达，但在结肠中没有显着增加，尽管饮食之间没有显着差异。这些结果表明，HFD 诱导的 IgA 对肠道微生物群的反应性降低部分有助于回肠炎症的发展，但不会导致肠道菌群失调。我们还发现，仅在 HFD 喂养下， Aicda缺乏会显着增加空腹血胰岛素水平。此外，单核细胞趋化蛋白1（一种导致高胰岛素血症发作的主要趋化因子）在肝脏中的基因表达因HFD喂养而显着增加，而Aicda则趋于增加。不足。这些发现表明，HFD 诱导的 IgA 对肠道微生物群的反应性降低，部分通过增加肝脏中单核细胞趋化蛋白 1 的表达而导致高胰岛素血症。