Short-term Efficacy And Mechanism Of Bifidobacterium Quadruple Viable Bacteria In Patients With Diarrhea-Predominant Irritable Bowel Syndrome

Objectives Irritable bowel syndrome(IBS)is one of the most common functional gastrointestinal disorders and diarrhea-predominant IBS(IBS-D)is the most common subtype.Owe to the high prevalence and recurrent unpleasant symptoms,IBS decreases patients’ life quality and brings huge economic burden to both patients and health system.Studies have shown that gut microbiota is closely related to the pathogenesis of IBS,but there is great heterogeneity among different clinical trials about probiotics in the treatment of IBS,leading to controversy about the reliability and efficacy of probiotics.This study aimd to evaluate the short-term efficacy of Bifidobacterium quadruple viable bacteria in patients with IBS-D,reveal the influence of this probiotics preparation on gut microbiota and metabolites,and explore factors associated with response to probiotics.MethodsA randomized,double-blind,placebo-controlled,multicenter trial was performed in 15 hospitals.290 patients who fulfilled the eligibility criteria were assigned to the probiotics or placebo group randomly with a ratio of 1:1 for a 4-week treatment and a 2-week followup.Response rate was determined as the primary outcome.It was regarded as the proportion of patients with composite responses of improvement in both abdominal pain and diarrhea simultaneously.The secondary outcomes included overall symptom relief,bowel frequency,bloating,urgency of defecation,use of remedial drugs,quality of life,depression score and anxiety score.Generalized linear model(GLM)was used to find differences in specific bacteria and metabolites between the probiotics and the placebo.ResultsAfter 4-week continuous administration,the response rates of the probiotics and the placebo were 67.59% and 36.55% respectively(P<0.001).Additionally,Bifidobacterium quadruple viable bacteria could also effectively improve the overall symptoms,reduce the frequency of defecation and decrease the degree of abdominal bloating.18 cases(12.4%)about adverse events were reported in the probiotics,whereas 17 cases(11.7%)reported in the placebo,showed no significant differences(P>0.05).In the probiotics,those with higher abdominal pain scores(2.674 [1.139,6.279])were more likely to respond but responders in placebo had lower Hamilton Depression Scale(HAMD)score(0.162 [0.060,0.439]),lower Hamilton Anxiety Scale(HAMA)score(0.335 [0.148,0.755])and higher degree of bloating(2.718 [1.217,6.074]).Although the diversity of the microbiota was not significantly changed by probiotics,the abundance of bacteria producing short chain fatty acids(SCFAs)including Butyricimonas(P=0.048),Pseudobutyrivibrio(P=0.005),Barnesiella(P=0.020)and Sutterella(P=0.020)increased.Besides,compared to the placebo,probiotics increased the concentration of SCFAs including butyric acid(P=0.010),valeric acid(P=0.019),caproic acid(P=0.046)and inhibited the decrease of propionic acid(P=0.028).ConclusionsBifidobacterium quadruple viable bacteria had a significant short-term efficacy for the treatment of IBS-D,and were more effective in patients with higher abdominal pain scores.This kind of probiotics could improve the abundance of several bacteria producing SCFAs as well as the concentration of fecal SCFAs compared to placebos.