A Randomised, Controlled Trial: Effect of a Multi-Strain Fermented Milk on the Gut Microbiota Recovery after Helicobacter pylori Therapy.

Eric Guillemard,Caroline Rossoni,Florent Schäfer,Muriel Derrien,Hania Szajewska,Frédéric Barbut,Peter Malfertheiner,Laurent Quinquis,Marion Poirel,Frank Wagner,Christian Keicher

doi:10.3390/nu13093171

Abstract

Helicobacter pylori (Hp) eradication therapy alters gut microbiota, provoking gastrointestinal (GI) symptoms that could be improved by probiotics. The study aim was to assess the effect in Hp patients of a Test fermented milk containing yogurt and Lacticaseibacillus (L. paracasei CNCM I-1518 and I-3689, L. rhamnosus CNCM I-3690) strains on antibiotic associated diarrhea (AAD) (primary aim), GI-symptoms, gut microbiota, and metabolites. A randomised, double-blind, controlled trial was performed on 136 adults under 14-day Hp treatment, receiving the Test or Control product for 28 days. AAD and GI-symptoms were reported and feces analysed for relative and quantitative gut microbiome composition, short chain fatty acids (SCFA), and calprotectin concentrations, and viability of ingested strains. No effect of Test product was observed on AAD or GI-symptoms. Hp treatment induced a significant alteration in bacterial and fungal composition, a decrease of bacterial count and alpha-diversity, an increase of Candida and calprotectin, and a decrease of SCFA concentrations. Following Hp treatment, in the Test as compared to Control group, intra-subject beta-diversity distance from baseline was lower (padj = 0.02), some Enterobacteriaceae, including Escherichia-Shigella (padj = 0.0082) and Klebsiella (padj = 0.013), were less abundant, and concentrations of major SCFA (p = 0.035) and valerate (p = 0.045) were higher. Viable Lacticaseibacillus strains were detected during product consumption in feces. Results suggest that, in patients under Hp treatment, the consumption of a multi-strain fermented milk can induce a modest but significant faster recovery of the microbiota composition (beta-diversity) and of SCFA production and limit the increase of potentially pathogenic bacteria.

Highlights

Antibiotics have been reported to alter gut microbiota to variable extents, which may lead to an increased prevalence of opportunistic pathogens, such as Clostridioides difficile (Cd), a decrease of the metabolism of primary bile acids and of non-digested carbohydrate, and a reduction of short-chain fatty acids (SCFA) production [1]
Several studies reported that Helicobacter pylori (Hp) treatments, including standard triple therapy, can induce alteration of gut microbiota that might persist for several months [7], with associated GI-symptoms including diarrhea in some studies [8,9]
One subject withdrew from the Test group before V3 due to Hp treatment intolerance but was included in the Full Analysis Set (FAS)

Summary

Introduction

Antibiotics have been reported to alter gut microbiota to variable extents, which may lead to an increased prevalence of opportunistic pathogens, such as Clostridioides difficile (Cd), a decrease of the metabolism of primary bile acids and of non-digested carbohydrate, and a reduction of short-chain fatty acids (SCFA) production [1]. A series of gastrointestinal (GI) symptoms, including antibiotic associated diarrhea (AAD), may result [1,3], and be responsible for treatment discontinuation and induction of antibiotic resistance, as reported in the case of Helicobacter pylori (Hp) eradication treatment [3]. Several studies reported that Hp treatments, including standard triple therapy, can induce alteration of gut microbiota that might persist for several months [7], with associated GI-symptoms including diarrhea in some studies [8,9]

Methods

Results

Discussion

Conclusion