Effect of Lacticaseibacillus rhamnosus IDCC 3201 on irritable bowel syndrome with constipation: a randomized, double-blind, and placebo-controlled trial

Abstract

Irritable bowel syndrome is a chronic disorder affecting the gastrointestinal tract, negatively impacting patients' quality of life. Here, we aimed to evaluate the effects of Lacticaseibacillus rhamnosus IDCC 3201 (RH 3201) on irritable bowel syndrome with constipation (IBS-C). In this randomised, double-blind, placebo-controlled trial, a total of 30 subjects with IBS-C were randomly assigned (1:1) to receive 8 weeks of probiotics administration or placebo. Concerning bowel activities, both irritant bowel movements and discomfort caused by constipation showed significant improvement with RH 3201 at 8 weeks. Symptoms including severity of abdominal bloating, frequency of abdominal bloating, and satisfaction of bowel habits based on the irritable bowel syndrome-severity scoring system also ameliorated in the probiotic group. Analysis of the fecal microbiome revealed that the abundance of Bacteroides cellulosilyticus and Akkermansia muciniphila was higher during the period of RH 3201 administration compared to the placebo. Untargeted metabolome analysis further suggested a correlation between specific metabolites, such as N-acetylornithine, xanthine, and 3-phenylpropionic acid, and the improvement of clinical symptoms. These results indicate that RH 3201 was effective in ameliorating IBS-C, potentially by enriching beneficial microbes and associated metabolites in the gut environment.

Fig. 1

CONSORT flow diagram in this study.

Fig. 2

Assessment of bowel activities in participants by RH 3201. (A) Number of times of irritant bowel movements. (B) Discomfort after bowel movements. (C) Discomfort caused by constipation. Data were expressed as mean ± standard deviation. Significant differences compared to the placebo group are indicated as * (p < 0.05) using independent samples t-test.

Fig. 3

Assessment of IBS-SSS scores in participants by RH 3201. (A) Total IBS-SSS score. (B) Severity of abdominal bloating. (C) Dissatisfaction of bowel habits. (D) Interference with quality of life. Data were expressed as mean ± standard deviation. Significant differences compared to the placebo group are indicated as * (p < 0.05), ** (p < 0.01) and *** (p < 0.001) using independent samples t-test.

Fig. 4

Assessment of IBS-QOL (Quality Of Life) in participants by RH 3201. (A) Dysphoria. (B) Interference with activity. (C) Body image. (D) Health worry. (E) Food avoidance. (F) Social reaction. (G) Relationship. (H) Total QOL score. Data were expressed as mean ± standard deviation. Significant differences compared to the placebo group are indicated as * (p < 0.05) and ** (p < 0.01) using independent samples t-test.

Fig. 5

Beta-diversity using non-metric multidimensional scaling (NMDS) and the Bray-Curtis dissimilarity index of fecal microbiome from the placebo and RH 3201 groups. Microbial communities of (A) baseline (0-week), (B) 4-week, and (C) 8-week between the placebo and RH 3202 groups. (D and E) Microbial communities in (D) placebo and (E) RH 3201 group during the intervention periods.

Fig. 6

Enrichment analysis at the species level between the placebo and RH 3201 group using linear discriminant effect size (LEfSe) analysis. Species differentially abundant in (A) placebo and (B) RH 3201 groups at 4-week, and (C) placebo and (D) RH 3201 at 8-week. Significant differences between the groups are indicated as * (p < 0.05) and ** (p < 0.01) using Mann Whitney U-test.

Fig. 7

Multivariate (A–E) and univariate (F–I) analyses of fecal metabolome over time of intervention in the placebo and RH 3201 groups. (A–C) Unsupervised principal component analysis (PCA) with an auto-scaling method. (D) Supervised partial least squares discriminant analysis (PLS-DA) with an auto-scaling method. (E) Discriminant metabolic features identified according to the Variable Importance in Projection (VIP) scores. The 15 most important metabolites with value of VIP score > 1.5 are reported. (F–I) Volcano plot analyses of differentially abundant fecal metabolites over time of intervention in the placebo and RH 3201 groups. RH 3201 versus placebo at 4-week (F) and 8-week (G). Changes on metabolite abundances of RH 3201 at 4-week (H) and 8-week (I) compared to the 0-week control. Blue and red dots represent significant decreases and increases in metabolites, respectively (p < 0.05). Gray dots represent all other metabolites identified in the dataset of which relative concentrations did not change significantly between the two groups.

Fig. 8

Relative abundances of specific metabolites highly abundant in the RH 3201 groups (A) and Spearman correlation analyses of clinical parameters (B) and fecal microbiome (C) with the metabolites. Metabolites differentially abundant in RH 3201 during the 8-weeks of intervention compared to the placebo group were selected (N-acetylornithine, xanthine, and 3-phenylpropionic acid), and their relative abundance was compared at 8-week (A). Significant differences between the groups are indicated as * (p < 0.05) using Mann Whitney U-test. For Spearman correlation, each row represents selected clinical questionnaires (B) and bacterial genera differentially abundant in RH 3201 compared to the placebo control at 8-week (C), and each column represents the selected metabolites. Red and blue are positive and negative correlation, respectively. Significant differences between the groups are indicated as * (p < 0.05).