Qingchang Wenzhong Decoction Accelerates Intestinal Mucosal Healing Through Modulation of Dysregulated Gut Microbiome, Intestinal Barrier and Immune Responses in Mice

Zhongmei Sun; Junxiang Li; Wenting Wang; Yuyue Liu; Jia Liu; Hui Jiang; Qiongqiong Lu; Panghua Ding; Rui Shi; Xingjie Zhao; Wenjing Yuan; Xiang Tan; Xiaojun Shi; Yunqi Xing; Tangyou Mao

doi:10.3389/fphar.2021.738152

Qingchang Wenzhong Decoction Accelerates Intestinal Mucosal Healing Through Modulation of Dysregulated Gut Microbiome, Intestinal Barrier and Immune Responses in Mice

Front Pharmacol. 2021 Sep 7:12:738152. doi: 10.3389/fphar.2021.738152. eCollection 2021.

Authors

Zhongmei Sun^{1

2}, Junxiang Li¹, Wenting Wang³, Yuyue Liu⁴, Jia Liu⁵, Hui Jiang¹, Qiongqiong Lu¹, Panghua Ding¹, Rui Shi¹, Xingjie Zhao¹, Wenjing Yuan⁶, Xiang Tan¹, Xiaojun Shi¹, Yunqi Xing¹, Tangyou Mao¹

Affiliations

¹ Department of Gastroenterology, Dongfang Hospital, Beijing University of Chinese Medicine, Beijing, China.
² Graduate School, Beijing University of Chinese Medicine, Beijing, China.
³ Department of Traditional Chinese Medicine, Beijing Yangfangdian Hospital, Beijing, China.
⁴ Department of Pathology, Dongfang Hospital, Beijing University of Chinese Medicine, Beijing, China.
⁵ School of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing, China.
⁶ Dongzhimen Hospital, Beijing University of Chinese Medicine, Beijing, China.

Abstract

Inflammatory bowel disease (IBD), a group of multifactorial and inflammatory infirmities, is closely associated with dysregulation of gut microbiota and host metabolome, but effective treatments are currently limited. Qingchang Wenzhong Decoction (QCWZD) is an effective and classical traditional herbal prescription for the treatment of IBD and has been proved to attenuate intestinal inflammation in a model of acute colitis. However, the role of QCWZD in recovery phase of colitis is unclear. Here, we demonstrated that mice treated with QCWZD showed a faster recovery from dextran sulfate sodium (DSS)-induced epithelial injury, accompanied by reduced mucosal inflammation and attenuated intestinal dysbiosis using bacterial 16S rRNA amplicon sequencing compared to those receiving sterile water. The protective effects of QCWZD are gut microbiota dependent, as demonstrated by fecal microbiome transplantation and antibiotics treatment. Gut microbes transferred from QCWZD-treated mice displayed a similar role in mucosal protection and epithelial regeneration as QCWZD on colitis in mice, and depletion of the gut microbiota through antibiotics treatments diminished the beneficial effects of QCWZD on colitis mice. Moreover, metabolomic analysis revealed metabolic profiles alternations in response to the gut microbiota reprogrammed by QCWZD intervention, especially enhanced tryptophan metabolism, which may further accelerate intestinal stem cells-mediated epithelial regeneration to protect the integrity of intestinal mucosa through activation of Wnt/β-catenin signals. Collectively, our results suggested that orally administrated QCWZD accelerates intestinal mucosal healing through the modulation of dysregulated gut microbiota and metabolism, thus regulating intestinal stem cells-mediated epithelial proliferation, and hold promise for novel microbial-based therapies in the treatment of IBD.

Keywords: Qingchang Wenzhong decoction; gut microbiota; inflammatory bowel disease; intestinal stem cells; mucosal healing; tryptophan metabolism.