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
ARTICLE HIGHLIGHTS
Research background

Irritable bowel syndrome (IBS) is a disorder of gut-brain interaction characterized by abdominal pain in association with altered bowel habits and further classified by the predominant stool pattern. Global prevalence is high, with diarrhea predominant subtype (IBS-D) considered the most common. IBS-D has a significant impact on quality of life, and clinical management remains challenging due to the variety of symptoms to address.

Research motivation

A recent meta-analysis showed probiotics to be safe and superior to placebo for alleviating global IBS-D symptoms. However, the certainty of evidence is low, due in part to significant heterogeneity between studies. There is therefore a need for well-powered randomized controlled trials on promising probiotic candidates for IBS-D.

Research objectives

To assess the efficacy of a probiotic candidate strain, Lactiplantibacillus plantarum (L. plantarum) Lpla33 (DSM34428), in adults with IBS-D. The primary outcome was the change in the IBS severity scoring system (IBS-SSS) total score after 8 wk. Additional outcomes included the change in abdominal pain severity, IBS-related quality of life, stool and microbial profile, and perceived stress.

Research methods

Adults meeting Rome IV diagnostic criteria for IBS-D were recruited from 12 gastroenterology specialized centers across India. In this randomized, double-blind, placebo-controlled, multi-center, parallel-arm, and dose-ranging study, a total of 307 adults meeting the inclusion criteria were allocated (1:1:1) to receive placebo or L. plantarum Lpla33 at one of two doses [1 × 109 colony-forming units (CFU)/d (1B) or 1 × 1010 CFU/d (10B)] over 8 wk.

Research results

The primary outcome, IBS-SSS total score, was significantly reduced after 8 wk in participants receiving L. plantarum compared to placebo (P < 0.001), with a dose-ranging effect when comparing the two L. plantarum groups (P < 0.05). In total, 59.6% and 72.6% of participants in the L. plantarum 1B and L. plantarum 10B groups, respectively, were considered significant responders based on a 95-point reduction threshold, as compared to 26.3% in the placebo group (P < 0.001). Additionally, 62.5% and 88.4% of participants administered L. plantarum 1B and 10B, respectively, demonstrated a significant reduction in diarrheal stool form as compared to 26.3% in the placebo group (P < 0.001).

Research conclusions

L. plantarum Lpla33 is well tolerated and demonstrates dose-ranging efficacy in alleviating IBS symptom severity with a corresponding normalization of bowel habits in adults with IBS-D.

Research perspectives

Future research should incorporate multi-omics analyses and associated biomarkers to better understand the mechanisms of action involved.