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Abstract: TH-PO0433

1-Kestose Enhances Luminal IgA and Improves IgA Deposition Under Intestinal Inflammation in High IgA (HIGA) Mice

Session Information

Category: Glomerular Diseases

  • 1401 Glomerular Diseases: Mechanisms, including Podocyte Biology

Authors

  • Ohyama, Yukako, Fujita Ika Daigaku, Toyoake, Aichi Prefecture, Japan
  • Tsuji, Yudai, Fujita Ika Daigaku, Toyoake, Aichi Prefecture, Japan
  • Fukasawa, Motoaki, Fujita Ika Daigaku, Toyoake, Aichi Prefecture, Japan
  • Tsuboi, Naotake, Fujita Ika Daigaku, Toyoake, Aichi Prefecture, Japan
  • Takahashi, Kazuo, Fujita Ika Daigaku, Toyoake, Aichi Prefecture, Japan
Background

Immunoglobulin A nephropathy (IgAN) is the most common form of primary glomerulonephritis worldwide. Although its pathophysiology remains incompletely understood, it is thought that nephritogenic properties of IgA1 are thought to be secreted by B cells originating or residing in mucosa-associated lymphoid tissues (MALT), such as Gut-ALT (GALT) and Nasopharynx-ALT (NALT). IgA production in MALT is believed to interact with the mucosal bacterial flora. Recently, “short-chain fatty acids (SCFAs)”, a metabolite of bacterial origin, have been reported to affect IgA production in MALT. 1-Kestose (KES), the smallest fructooligosaccharide, has been reported to increase SCFAs in the cecal contents of rats. Using a DSS-induced chronic colitis model in HIGA mice, we investigated how intestinal inflammation contributes to the pathogenesis of IgAN and evaluated the effects of oral KES administration on colitis-induced IgA nephropathy.

Methods

14-week-old female HIGA mice were divided into four groups; control, DSS-treated, KES-treated, and DSS+KES-treated. DSS was dissolved in sterilized drinking water and administered in three cycles for seven days at 14 days interval. Intestinal microorganisms were analyzed using 16s rDNA sequencing, and SCFA were measured using GC/MS. Serum and fecal IgA levels were measured using enzyme-linked immunosorbent assays (ELISA). The glomerular deposition rates of IgA in renal specimens were measured using immunofluorescence.

Results

DSS administration altered the intestinal microbiota. LEfSe analysis showed increases in mucin-degrading bacteria (Bacteroides acidifaciens, Akkermansia muciniphila) and decreases in Alloprevotella and Lactobacillus helveticus, all of which were restored by KES administration. DSS reduced cecal propionate levels, which were recovered by KES . KES increased the percent change in serum IgA regardless of colitis (P = 0.0165, 0.0348) and enhanced intestinal IgA secretion during colitis (P = 0.0188). Glomerular IgA deposition increased with colitis induction and tended to improve with KES treatment (P = 0.0094).

Conclusion

KES administration mitigated DSS-induced alterations in the gut microbiota and SCFAs, and by promoting luminal IgA secretion, may block microbial translocation and consequently attenuate pro-inflammatory responses within GALT, ultimately contributing to the amelioration of IgAN.

Funding

  • Government Support – Non-U.S.