Modulation of Gut Mucosal Microbiota As a Mechanism of Probiotics-Based Adjunctive Therapy for Ulcerative Colitis

Abstract

Background: Ulcerative colitis (UC) is a chronic subtype of inflammatory bowel disease (IBD), and is associated with gut microbiota. The aim of the present study was to evaluate the effects of probiotics as adjunctive treatment for ulcerative colitis. Methods: Twenty-five active UC subjects were assigned two groups (probiotic group, n=12; placebo group, n=13). The probiotic group received oral probiotics twice daily plus the standard drug regimen (mesalazine at a dose 60 mg / kg / day) for 12 weeks, while the placebo group received only the standard drug regimen. Findings: The trial outcomes were assessed at week 0 and week 12 by clinical assessment and profiling the gut mucosa microbiota by samples at week 0 and week 12 were analyzed using PacBio single-molecule, real-time sequencing (SMRT) of full-length 16S rRNA. We observed a significantly greater reduction in ulcerative colitis disease activity index (UCDAI) in the probiotic group compared with the placebo group (P=0.043), accompanying by a higher remission rate (91.67% for probiotic-receivers versus 69.23% for placebo-receivers, P=0.034). The gut mucosal microbiota of the probiotic-receivers had significantly more beneficial bacteria, such as Eubacterium ramulus (P<0.05), Pediococcus pentosaceus (P<0.05), Bacteroides fragilis (P=0.02), and Weissella cibaria (P=0.04). Additionally, these beneficial bacteria correlated negatively and significantly with UCDAI, suggesting that the probiotics might have contributed to improve UC by modulating the gut mucosal microbiota. Interpretation: Our research has provided new insights into the mechanism of the symptom alleviation effects of probiotics as adjuctive treatment for UC. Funding: This research was supported by the National Natural Science Foundation of China (31720103911), Inner Mongolia Science & Technology Major Projects (ZDZX2018018). Declaration of Interest: The authors declare that they have no conflict of interest. Ethical Approval: All subjects provided written informed consent prior to the start of the study. The Ethical Committees of Inner Mongolia Agriculture University and the Affiliated Hospital of Inner Mongolia Medical University approved the study. The study was registered in Chinese Clinical Trial Registry (chiCTR-IPR-17010306).