The effect of Clostridium butyricum on symptoms and fecal microbiota in diarrhea-dominant irritable bowel syndrome: a randomized, double-blind, placebo-controlled trial

Abstract

Irritable bowel syndrome (IBS) is a common disorder in gastrointestinal system and impairs the quality of life of the patients. Clostridium butyricum (CB) is a probiotics that has been used in several gastrointestinal diseases. The efficacy of CB in treating IBS is still unknown. This prospective, multi-centre, randomized, double-blind, placebo-controlled trial aimed to assess the efficacy and safety of CB in treating diarrhea-predominant IBS (IBS-D) and analyze the fecal microbiota after treatment. Two hundred patients with IBS-D were recruited and were given CB or placebo for 4 weeks. End points included change from baseline in IBS symptoms, quality of life, stool consistency and frequency. Compared with placebo, CB is effective in improving the overall IBS-D symptoms (-62.12 ± 74.00 vs. -40.74 ± 63.67, P = 0.038) as well as quality of life (7.232 ± 14.06 vs. 3.159 ± 11.73, P = 0.032) and stool frequency (-1.602 ± 1.416 vs. -1.086 ± 1.644, P = 0.035). The responder rates are found higher in CB compared with the placebo (44.76% vs. 30.53%, P = 0.042). The change in fecal microbiota was analyzed and function pathways of CB in treating IBS-D were predicted. In conclusion, CB improves overall symptoms, quality of life and stool frequency in IBS-D patients and is considered to be used as a probiotics in treating IBS-D clinically.

Figure 1

Flow chart of this study. Reasons for discontinuation are shown.

Figure 2

Responder rate after treatment in placebo and Clostridium butyricum (CB) groups. The overall responder rate was higher in the CB group compared with that in the placebo group (P = 0.042). The responder rate of patients with moderate to severe symptoms in the CB group was significantly higher than that in the placebo group (P = 0.007). *P < 0.05, **P < 0.01.

Figure 3

The improvement of stool consistency and frequency in placebo and Clostridium butyricum (CB) groups. (a) No significant difference was found in change of Bristol stool scale from baseline to week 4 between the CB group and the placebo group (P = 0.259). (b) The reduction of stool frequency in CB group was significantly superior than that in the placebo group (P = 0.035). *P < 0.05.

Figure 4

16 s rRNA pyrosequencing analysis of stool samples. (a) Wilcoxon test of Sob index showed an increased tendency after treating with Clostridium butyricum (CB) (P = 0.063). (b) Heat-map plot with 30 most abundant OTUs in all stool samples. (c) Two clusters were observed using Fisher’s exact test. (d,e) The PCoA plot of placebo and CB groups in baseline and week 4.

Figure 5

Metagenomic analysis of stool samples. (a) ANOSIM analysis of eggNOG between placebo and Clostridium butyricum (CB) groups at baseline and week 4. (b) ANOSIM analysis of KEGG between placebo and CB groups at baseline and week 4. No significant differences were observed between two groups in baseline and week 4 for eggNOG (P = 0.569 in baseline, P = 0.918 in week 4) and KEGG (P = 0.707 in baseline, P = 0.746 in week 4) analysis. (c,d) LEfSe analysis of KEGG pathways between placebo and CB groups at baseline and week 4. (e,f) LDA score of LEfSe analysis at baseline and week 4. (g,h) STAMP analysis of KEGG pathways between placebo and CB groups at baseline and week 4.

Figure 6

The whole metabolic pathways of Clostridium butyricum (CB) and placebo via iPath. The blue lines were metabolic pathways dominant in CB group. The red lines were metabolic pathways dominant in placebo group. The green lines were co-pathways in both groups. (a) The metabolic pathways of two groups at baseline. (b) The metabolic pathways of two groups at week 4.