Association between gut microbiota and mucosal regulartory T cells in dogs with breed-specific inflammatory bowel disease

2018 Fiscal Year Final Research Report

• Project/Area Number: 16K18801
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Veterinary medical science
• Research Institution: Azabu University (2017-2018); Rakuno Gakuen University (2016)
• Principal Investigator: Igarashi Hirotaka 麻布大学, 獣医学部, 講師 (20758172)
• Project Period (FY): 2016-04-01 – 2019-03-31
• Keywords: 腸内細菌叢 / 短鎖脂肪酸 / 制御性T細胞 / 粘膜免疫 / ミニチュア・ダックスフンド / 炎症性ポリープ

Outline of Final Research Achievements

This study evaluated the association between fecal dysbiosis and concentration of short chain fatty acids (SCFAs), and distribution of regulatory T cells (Tregs) in canine inflammatory colorectal polyp (ICRP).
HPLC revealed a decreased fecal propionate concentration in ICRP-affected dogs. ICRP cases had fewer amount of fecal Bifidobacterium. Fecal composition of Bifidobacterium, Firmicutes, and Lactobacillus significantly correlated with the total SCFA concentrations. Immunohistochemistry and qPCR analysis on the mucosal tissues revealed an increased number of Tregs and upregulation of IL-1b, IL-6, IL-8, IL-10, IL-17, IL-22, IFN-r, TNF-a, and TGF-b genes in the polyp. However, the rate of increase in IL-10 gene expression was significantly lower than that of IL-1b, IL-6, and IL-8.
These results suggest that the reduced SCFA-producing bacteria results in the decreased fecal SCFA concentration, which may lead to the weak recruitment of Tregs and anti-inflammatory cytokines in ICRP lesion.

Free Research Field

獣医内科学

Academic Significance and Societal Importance of the Research Achievements

本研究により、犬種特異的な炎症性結直腸ポリープにおける腸内細菌叢と短鎖脂肪酸の変動およびその関連性が明らかとなり、さらにポリープ病変部における制御性T細胞をはじめとした粘膜免疫の動態について基礎的な知見を得ることができた。この内容は、今後の炎症性ポリープに対する現状の治療法である免疫抑制療法に加えて、腸内細菌叢や短鎖脂肪酸が新規治療ターゲットとなりうる可能性を示唆している。また今回得られた知見は、NOD2機能亢進症であるブラウ症候群や大腸の化膿性炎症性疾患である潰瘍性大腸炎などの病態解明の一助になることを期待している。