Clinical Trials Study
Copyright ©The Author(s) 2023. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Jul 28, 2023; 29(28): 4451-4465
Published online Jul 28, 2023. doi: 10.3748/wjg.v29.i28.4451
Efficacy and dose response of Lactiplantibacillus plantarum in diarrhea-predominant irritable bowel syndrome
Christopher J Martoni, Shalini Srivastava, Anders Damholt, Gregory J Leyer
Christopher J Martoni, Anders Damholt, Clinical Development, Human Health, Chr. Hansen A/S, Hoersholm 2970, Denmark
Shalini Srivastava, Clinical Development, Vedic Lifesciences, Mumbai 400053, India
Gregory J Leyer, Scientific Affairs,Human Health, Chr. Hansen A/S, Hoersholm 2970, Denmark
Author contributions: Martoni CJ, Damholt A, and Leyer GL conceived, designed, and planned the study; Srivastava S directed the study, data analysis, and reporting; Martoni CJ prepared the original manuscript; Srivastava S, Damholt A, and Leyer GL reviewed and edited the manuscript; and all authors have read and approved the final version.
Institutional review board statement: This study was approved and monitored by an independent ethics committee (Approval No: VED/P-20/22/JUL/2021).
Clinical trial registration statement: This study was prospectively registered on clinicaltrials.gov under study number NCT04950296. The registry URL is as follows: https://clinicaltrials.gov/ct2/show/NCT04950296.
Informed consent statement: All study participants provided their voluntary written informed consent prior to their inclusion.
Conflict-of-interest statement: The study was funded by Chr. Hansen A/S. Christopher J Martoni, Anders Damholt and Gregory J Leyer are employees of Chr. Hansen A/S but were not involved in the study conduct, data management, or statistical analysis.
Data sharing statement: The anonymized data presented in this study are available on request from the corresponding author.
CONSORT 2010 statement: The authors have read the CONSORT 2010 Statement, and the manuscript was prepared and revised according to the CONSORT 2010 Statement.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: https://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Christopher J Martoni, PhD, Senior Scientist, Clinical Development, Human Health, Chr. Hansen A/S, 10-12 Boege Alle, Hoersholm 2970, Denmark. cachma@chr-hansen.com
Received: June 9, 2023
Peer-review started: June 9, 2023
First decision: June 14, 2023
Revised: June 27, 2023
Accepted: July 11, 2023
Article in press: July 11, 2023
Published online: July 28, 2023
Processing time: 46 Days and 17.4 Hours
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 Lactiplantibacillus plantarum (L. plantarum) 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 L. plantarum Lpla33 at 1 × 109 (1B) or 1 × 1010 (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 L. plantarum 1B (-128.45 ± 83.30; P < 0.001) and L. plantarum 10B (-156.77 ± 99.06; P < 0.001), compared to placebo (-58.82 ± 74.75). Further, a dose-ranging effect was observed, with a greater absolute reduction in the L. plantarum 10B group (P < 0.05). A reduction in sub-scores related to abdominal pain, abdominal distension, bowel habits, and quality of life was observed in both L. plantarum groups compared to placebo (P < 0.001). Further, 62.5% and 88.4% of participants administered L. plantarum 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 (P < 0.001). In contrast, no significant shifts were observed in microbial diversity.

CONCLUSION

L. plantarum 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.

Keywords: Randomized clinical trial; Diarrhea-predominant irritable bowel syndrome; Microbiome; Probiotic; Lactiplantibacillus plantarum

Core Tip: The current study is unique in its dose-ranging assessment of a Lactiplantibacillus plantarum (L. plantarum) probiotic strain in a well-powered multi-center randomized controlled trial in adults with diarrhea-predominant irritable bowel syndrome (IBS-D). L. plantarum Lpla33 (DSM34428) was well tolerated and significantly improved global IBS symptom scores as compared to placebo, both at an absolute level and in the number of clinically relevant responders. Further, a dose-ranging effect was observed in global IBS symptom scores, abdominal pain severity, quality of life, and normalization of diarrheal stool type.