Indigo Naturalis Alleviates Dextran Sulfate Sodium-Induced Colitis in Rats via Altering Gut Microbiota

Zhongmei Sun; Junxiang Li; Yi Dai; Wenting Wang; Rui Shi; Zhibin Wang; Panghua Ding; Qiongqiong Lu; Hui Jiang; Wenjing Pei; Xingjie Zhao; Yi Guo; Jiali Liu; Xiang Tan; Tangyou Mao

doi:10.3389/fmicb.2020.00731

Indigo Naturalis Alleviates Dextran Sulfate Sodium-Induced Colitis in Rats via Altering Gut Microbiota

Front Microbiol. 2020 Apr 30:11:731. doi: 10.3389/fmicb.2020.00731. eCollection 2020.

Authors

Zhongmei Sun^{1

2}, Junxiang Li², Yi Dai³, Wenting Wang⁴, Rui Shi², Zhibin Wang², Panghua Ding^{1

2}, Qiongqiong Lu^{1

2}, Hui Jiang², Wenjing Pei², Xingjie Zhao², Yi Guo⁵, Jiali Liu^{1

2}, Xiang Tan², Tangyou Mao²

Affiliations

¹ Graduate School, Beijing University of Chinese Medicine, Beijing, China.
² Department of Gastroenterology, Dongfang Hospital, Beijing University of Chinese Medicine, Beijing, China.
³ Department of Pharmacy, School of Pharmacy, Hyogo University of Health Sciences, Kobe, Japan.
⁴ Department of Traditional Chinese Medicine, Beijing Yangfangdian Hospital, Beijing, China.
⁵ Department of Gastroenterology, Dongzhimen Hospital, Beijing University of Chinese Medicine, Beijing, China.

Abstract

Ulcerative colitis is a gastrointestinal disorder intricately associated with intestinal dysbiosis, but effective treatments are currently limited. Indigo naturalis, a traditional Chinese medicine derived from indigo plants, has been widely used in the treatment of ulcerative colitis. However, the specific mechanisms have not yet been identified. Accordingly, in this study, we evaluated the effects and mechanisms of indigo naturalis on dextran sulfate sodium (DSS)-induced colitis in rats. Our results showed that indigo naturalis potently alleviated DSS-induced colitis in rats, and reversed DSS-induced intestinal dysbiosis using bacterial 16S rRNA amplicon sequencing. The protective effects of indigo naturalis were gut microbiota dependent, as demonstrated by antibiotic treatments and fecal microbiota transplantation. Depletion of the gut microbiota through a combination of antibiotic treatments blocked the anti-inflammatory effect of indigo naturalis on the DSS-induced colitis, and the recipients of the gut microbiota from indigo naturalis-treated rats displayed a significantly attenuated intestinal inflammation, which was actively responsive to therapeutic interventions with indigo naturalis. Notably, supplement with indigo naturalis greatly increased the levels of feces butyrate, which was positively correlated with the relative abundances of Ruminococcus_1 and Butyricicoccus. We further showed that indigo naturalis-dependent attenuation of colitis was associated with elevated expression of short-chain fatty acid-associated receptors GPR41 and GPR43. Collectively, these results suggested that indigo naturalis alleviates DSS-induced colitis in rats through a mechanism of the microbiota-butyrate axis, particularly alterations in Ruminococcus_1 and Butyricicoccus abundances, and target-specific microbial species may have unique therapeutic promise for ulcerative colitis.

Keywords: butyrate; dextran sulfate sodium; gut microbiota; indigo naturalis; ulcerative colitis.