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.
Highlights
Ulcerative colitis (UC) is one major phenotype of inflammatory bowel disease (IBD), characterized by chronic, continuous, recurrent colonic mucosal inflammation of the colon, affecting the rectum and extending to proximal colon continuously, with typical clinical symptoms including bloody diarrhea, abdominal pain, fecal urgency, and tenesmus (Magro et al, 2017; Feuerstein et al, 2019)
We aimed to seek the answer from traditional Chinese medicine, and our results revealed that Qingchang Wenzhong Decoction treatment resulted in rapid recovery from intestinal inflammation and mucosal damages
Metabolomic analysis showed metabolic profiles alternations in response to the gut microbiota reprogrammed by Qingchang Wenzhong Decoction (QCWZD) intervention, especially enhanced tryptophan metabolism, which may further accelerates intestinal stem cells-mediated epithelial regeneration to protect the integrity of intestinal mucosa through activation of Wnt/β-catenin signals
Summary
Ulcerative colitis (UC) is one major phenotype of inflammatory bowel disease (IBD), characterized by chronic, continuous, recurrent colonic mucosal inflammation of the colon, affecting the rectum and extending to proximal colon continuously, with typical clinical symptoms including bloody diarrhea, abdominal pain, fecal urgency, and tenesmus (Magro et al, 2017; Feuerstein et al, 2019). Corticosteroids, thiopurines, folic acid antagonists, and biological therapies are focused on decreasing intestinal inflammation, inducing and extending disease remission, and controlling complications (Ungaro et al, 2017; Turner et al, 2021) These approaches are not curative and have several limitations such as low responsiveness, allergy responses, opportunistic infections, excessive immunosuppression, and refractoriness (Stallmach et al, 2010; Hazel and OConnor, 2020). Despite the microbial-based therapeutic approaches including fecal microbiota transplantation and probiotics have been explored as promising candidates to reprogram microbial balance, epithelial integrity and immune homeostasis, leading to the remission and recovery of colitis (Koretz, 2018; Sood et al, 2021), there is still no consensus on such treatments in UC as a potential clinical strategy, just because of existed challenges such as reliability, safety, and standardization (Narula et al, 2017; Levy and Allegretti, 2019; Cheng and Fischer, 2020)
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