Deoxycholic acid exacerbates intestinal inflammation by modulating interleukin-1 β expression and tuft cell proportion in dextran sulfate sodium-induced murine colitis

PeerJ

article

Jingyi Ju¹  Cui Zhang¹  Jiaolan Yang¹  Qinglu Yang¹  Pengyun Yin¹  Xiaomin Sun¹ 

[1] Gastroenterology Department, The Shanghai Tenth People’s Hospital;Medical College, Tongji University

关键词: Inflammatory bowel disease;    Deoxycholic acid;    Secondary bile acids;    IL-1β;    Intestinal flora;    Tuft cells;   

DOI  :  10.7717/peerj.14842

学科分类：社会科学、人文和艺术（综合）

来源: Inra

【 摘 要 】

BackgroundThe etiology of inflammatory bowel disease (IBD) remains unclear. However, intestinal metabolism is known to be critical in the pathogenesis of IBD. Bile acid is one of the main intestinal metabolites, and its role in the pathogenesis of IBD is worthy of investigation. This study investigated the role of deoxycholic acid (DCA), a bile acid, in the pathogenesis of IBD.MethodsPeripheral serum metabolomics, fecal metabolomics, and microbiome analyses were performed on patients with IBD and healthy controls. Flow cytometry, real-time quantitative polymerase chain reaction, western blotting, enzyme-linked immunosorbent assay, immunohistochemical staining, and immunofluorescence analysis were used to evaluate cytokines in the inflamed colonic mucosa and immune cells and tuft cells in the intestine of mice with dextran sulfate sodium (DSS)-induced colitis.ResultsIn total, 156 patients with IBD and 58 healthy controls were enrolled. DCA levels in the serum and feces of patients with IBD were significantly decreased compared to the controls. This decrease was associated with a decrease in the abundance of intestinal flora, including Firmicutes, Clostridia, Ruminnococcaceae, and Lachnospiraceae. Additionally, interleukin (IL)-1β levels in the serum of patients with active Crohn’s disease were significantly increased compared with the healthy controls. Moreover, in DCA-treated DSS-induced mice, the expression of IL-1β and the proportion of CD3+ and CD4+ T cells increased while the number of intestinal tuft cells decreased, compared with the DSS group.ConclusionIn IBD patients, the decreased DCA levels in serum and fecal samples are associated with disturbances in gut microflora diversity and abundance. Possible mechanisms by which DCA affects immunity in DSS-induced murine colitis include increasing IL-1β secretion, reducing the number of tuft cells in the mucosa, and activating CD4+ and CD3+ T cells to exaggerate immune responses, consequently worsening intestinal inflammation.

【 授权许可】

CC BY