Article - Efficacy and dose response of in diarrhea-predominant irritable bowel syndrome.

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Take home message

This randomised, double-blind, placebo controlled, multi-centre, parallel-arm and dose-ranging study showed that L. plantarum may be a strong candidate for the management of IBS-D symptoms and associated mental health effects.
L. plantarum may be of particular benefit to individuals who are suffering from stress because of IBS-D.
L. plantarum is well tolerated and may be of benefit to individuals who have ceased pharmaceutical treatments as a result of side-effects.

Evidence category

A: Meta-analyses, position-stands, randomized-controlled trials (RCTs)

Summary review

Introduction

This study aimed to determine the tolerability and efficacy of varying supplemental doses of Lactiplantibacillus plantarum (Lpla33) in adults with irritable bowel syndrome of the diarrhoea predominant subtype (IBS-D).

Methods

This randomised, double blind, placebo-controlled trial recruited 307 females and males aged 18-70 years with IBS-D based upon the Rome IV diagnostic criteria with Bristol Stool Scale stools of type 6 or 7.

Individuals were randomised to receive an eight-week intervention in one of three study groups: Group 1B: Lpla33 at 1 × 109 vs group 10B: 1x1010 colony forming units (CFU) per day vs placebo.

Results

Improvement was seen in the primary outcome of IBS-D symptom severity (IBS-SSS) with both Lpla33 doses compared to placebo at the end of the trial (P=<0.001).
Improvements with both doses compared to placebo were seen as quickly as 28 days (P=<0.01).
At the end of the study the higher dose Lpla33 was more effective at improving IBS-SSS compared to the lower dose (P=<0.05).
Improvements to IBS remission or mild IBS were seen in 48.1% in group 1B, 72.6% in group 10B and only 11.1% of placebo (P=<0.001).
Specific improvements were seen in 10B group compared to placebo in abdominal pain severity and duration, abdominal distension, bowel habits, and quality of life (QoL) (P=<0.001).
Post-hoc analysis showed that supplementation prevented symptom development compared to placebo with 2.9% of group 1B, 2.1% of group 10B and 18.2% of placebo individuals reporting increased symptom severity (P=<0.001).
QoL and perceived stress were improved with supplementation compared to placebo (P=<0.001 for both), with the higher dose being more beneficial than the lower dose in QoL (P=<0.001).
Compliance to Lpla33 was comparable to placebo (P=>0.05), with adverse events related to the supplement including nausea and vomiting.

Conclusion

L. plantarum at doses of 1 × 109 and 1 × 1010 CFU/day is a well-tolerated and efficacious therapy for the improvement of symptoms related to IBS-D, with benefits seen as quickly as 28 days after commencing supplementation.
Symptoms such as abdominal pain severity and duration, QoL and perceived stress may all be improved.
Stool normalisation may be seen in certain individuals.

Clinical practice applications

L. plantarum supplementation may be of benefit to the management and improvement of symptoms in individuals with IBS-D.
Improvements may be seen physically and in mental health parameters.
Metronidazole (400mg/day) was given as a rescue medication for individuals with severe pain and frequent loose stools and should be considered when interpreting results.

Considerations for future research

The authors concluded that future research should focus on understanding the mechanisms of action that may be involved.
Studying the role of diet on the microbial community and metabolite profiles in IBS-D may be of interest.

Abstract

BACKGROUND

Probiotics have shown promise in alleviating symptoms of diarrhea-predominant irritable bowel syndrome (IBS-D); however, the certainty of evidence is low. Well-powered randomized controlled dose-ranging trials are warranted on promising single-strain candidates.

AIM

To investigate the clinical efficacy of () Lpla33 (DSM34428) in adults with IBS-D.

METHODS

This is a randomized, double-blind, placebo-controlled, multi-center, and dose-ranging study. Three hundred and seven adults, 18-70 years of age, with IBS-D, according to Rome IV criteria, were allocated (1:1:1) to receive placebo or Lpla33 at 1 × 10 (1B) or 1 × 10 (10B) colony-forming units/d over an 8-wk intervention period. The primary outcome was the change in IBS severity scoring system (IBS-SSS) total score after 8 wk, while secondary and exploratory outcomes included abdominal pain severity, IBS related quality of life, stool and microbial profile, and perceived stress.

RESULTS

IBS-SSS was significantly reduced, after 8 wk, in participants receiving 1B (-128.45 ± 83.30; < 0.001) and 10B (-156.77 ± 99.06; < 0.001), compared to placebo (-58.82 ± 74.75). Further, a dose-ranging effect was observed, with a greater absolute reduction in the 10B group ( < 0.05). A reduction in sub-scores related to abdominal pain, abdominal distension, bowel habits, and quality of life was observed in both groups compared to placebo ( < 0.001). Further, 62.5% and 88.4% of participants administered 1B and 10B, respectively, were classified as stool consistency responders based on a reduction in diarrheal stool form, as compared to 26.3% in the placebo group ( < 0.001). In contrast, no significant shifts were observed in microbial diversity.

CONCLUSION

Lpla33 (DSM34428) is well tolerated and improves IBS symptom severity with a dose-ranging effect and a corresponding normalization of bowel habits in adults with IBS-D.