抗炎治疗改善肠道损伤和菌群稳态,或可减少1型糖尿病
创作:吴芹 审核:Zhonghua 02月26日
  • 1型糖尿病(T1D)小鼠肠黏膜中,细胞因子IL-17A、IL-22和IL-23A表达显著降低,与其表达相关的免疫细胞数量减少;
  • T1D小鼠中肠黏膜功能改变,肠屏障受损,回肠中诱导IL17、IL-22和IL23A表达的分节丝状菌(SFB)进行性减少;
  • 在Trac-/- T细胞缺陷小鼠中导入T1D小鼠T细胞可以导致肠黏膜改变;
  • 无炎症的高血糖小鼠不产生肠黏膜改变;
  • 抗炎治疗能恢复T1D小鼠肠黏膜和免疫细胞功能,维持肠稳态,保护肠道菌群,降低T1D发生率。
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Zhonghua
I型糖尿病(T1D)通常伴随有肠黏膜的损伤,表现为肠屏障功能破坏,炎性细胞浸润,诱导相关细胞因子表达的分节丝状菌(SFB)的减少,但是导致这些肠道病理改变的原因并不明确。近期一篇发表在Gut上的研究工作证实I型糖尿病中肠黏膜功能的改变与T1D介导的促炎反应有关,与高血糖无直接关系。经过抗炎治疗可以显著改善T1D中肠粘膜功能的损伤,保护肠道菌群稳态,从而降低T1D的发生率。
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Gut [IF:19.819]

Gut mucosa alterations and loss of segmented filamentous bacteria in type 1 diabetes are associated with inflammation rather than hyperglycaemia

1型糖尿病的肠粘膜改变和分节丝状菌(SFB)的减少与炎症而不是高血糖有关

10.1136/gutjnl-2020-323664

02-17, Article

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Objective : Type 1 diabetes (T1D) is an autoimmune disease caused by the destruction of pancreatic β-cells producing insulin. Both T1D patients and animal models exhibit gut microbiota and mucosa alterations, although the exact cause for these remains poorly understood. We investigated the production of key cytokines controlling gut integrity, the abundance of segmented filamentous bacteria (SFB) involved in the production of these cytokines, and the respective role of autoimmune inflammation and hyperglycaemia.
Design: We used several mouse models of autoimmune T1D as well as mice rendered hyperglycaemic without inflammation to study gut mucosa and microbiota dysbiosis. We analysed cytokine expression in immune cells, epithelial cell function, SFB abundance and microbiota composition by 16S sequencing. We assessed the role of anti-tumour necrosis factor α on gut mucosa inflammation and T1D onset.
Results: We show in models of autoimmune T1D a conserved loss of interleukin (IL)-17A, IL-22 and IL-23A in gut mucosa. Intestinal epithelial cell function was altered and gut integrity was impaired. These defects were associated with dysbiosis including progressive loss of SFB. Transfer of diabetogenic T-cells recapitulated these gut alterations, whereas induction of hyperglycaemia with no inflammation failed to do so. Moreover, anti-inflammatory treatment restored gut mucosa and immune cell function and dampened diabetes incidence.
Conclusion: Our results demonstrate that gut mucosa alterations and dysbiosis in T1D are primarily linked to inflammation rather than hyperglycaemia. Anti-inflammatory treatment preserves gut homeostasis and protective commensal flora reducing T1D incidence.

First Authors:
Matthieu Rouland,Lucie Beaudoin,Ophélie Rouxel,Léo Bertrand

Correspondence Authors:
Agnès Lehuen

All Authors:
Matthieu Rouland,Lucie Beaudoin,Ophélie Rouxel,Léo Bertrand,Lucie Cagninacci,Azadeh Saffarian,Thierry Pédron,Dalale Gueddouri,Sandra Guilmeau,Anne-Françoise Burnol,Latif Rachdi,Asmaa Tazi,Juliette Mouries,Maria Rescigno,Nathalie Vergnolle,Philippe Sansonetti,Ute Christine Rogner,Agnès Lehuen

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