Aicda deficiency exacerbates high-fat diet-induced hyperinsulinemia but not gut dysbiosis in mice.

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.

Cyclic nigerosylnigerose ameliorates DSS-induced colitis with restoration of goblet cell number and increase in IgA reactivity against gut microbiota in mice.

Cyclic nigerosylnigerose (CNN) is a cyclic oligosaccharide. Oral administration of CNN promotes immunoglobulin A (IgA) secretion in the gut. IgA is a major antibody secreted into the gut and plays a crucial role in suppressing gut inflammation due to commensal gut microbiota. To investigate the effect of administration of CNN to promote IgA secretion on gut inflammation, experimental colitis was induced with dextran sulfate sodium (DSS) in Balb/c mice after 6 weeks of CNN pre-feeding. The severity of colitis was evaluated based on a disease activity index (DAI), the gene expression of inflammatory cytokines, and a histological examination. The CNN-treated mice with DSS-induced colitis (CNN-DSS group) showed significantly lower DAI scores and mRNA levels of interleukin-1 compared with the CNN-untreated mice with DSS-induced colitis (DSS group). Histological examination of the colon revealed that the pathological score was significantly lower in the CNN-DSS group compared with the DSS group due to the reduced infiltration of immune cells. The number of goblet cells was significantly higher in the CNN-DSS group compared with the DSS group. The IgA concentration and the ratio of microbiota coated with IgA were evaluated in the cecal content. Although there was no difference in the IgA concentration among groups, a higher proportion of cecal microbiota were coated with IgA in the CNN-DSS group compared with that in the DSS group. These results suggest that CNN might preserve goblet cells in the colon and promote IgA coating of gut microbiota, which synergistically ameliorate gut inflammation in mice with DSS-induced colitis.

High-fat diet reduces the level of secretory immunoglobulin A coating of commensal gut microbiota.

Excessive fat intake is associated with changes in gut microbiota composition. In the present study, we focused on the secretory immunoglobulin A (SIgA) coating of gut microbiota as a mucosal immune response affecting the gut microbiota following a high-fat diet (HFD). The level of SIgA coating of gut microbiota was evaluated in normal-fat diet (NFD)- and HFD-fed mice. HFD significantly decreased the level of SIgA coating the gut microbiota compared with NFD. Of note, substitution of HFD with NFD resulted in a complete recovery of the level of SIgA coating. These findings suggest that dietary fat influences the SIgA coating of the gut microbiota. Furthermore, we analyzed the composition of the gut microbiota and the concentration of cecal short-chain fatty acids. HFD feeding changed the gut microbiota composition at the phylum and family levels. Pearson correlation analysis between the level of SIgA coating of gut microbiota and the relative abundance of gut microbiota showed that the relative abundances of Clostridiaceae, Mogibacteriaceae, Turicibacteraceae, and Bifidobacteriaceae were negatively correlated with the level of SIgA coating of gut microbiota. Conversely, the relative abundances of Desulfovibrionaceae, S24-7, and Lactobacillaceae were positively correlated with the level of SIgA coating. The concentrations of cecal acetate and butyrate were lower in HFD-fed mice and positively correlated with the level of SIgA coating of gut microbiota. Our observations suggest that a decrease in the level of SIgA coating of the gut microbiota through a HFD might relate to HFD-induced changes in microbial composition and microbial metabolites production.