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

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.

Improved gut microbiome recovery following drug therapy is linked to abundance and replication of probiotic strains

“…No significant difference that could impact the evaluation of product effect was observed between groups for major known confounding factors of gut microbiota such as age, sex, BMI, physical activity, dietary intake (including dietary fiber or alcohol), and smoking habits (Table S1). 24 Additionally, the proportion of Test and Control subjects with successful eradication of Hp was similar between both groups (>80%) (Table S1). Fecal samples from 135 subjects (67 in Test and 68 in Control group) collected at four time points, baseline (D0), end of Hp eradication therapy (D14), and 2 and 4 weeks after therapy (D28, D42), were available for the current study and subjected to deep WMS.…”

“…The fecal samples analyzed here were previously collected during a randomized, double-blind, controlled trial in subjects presenting infection with Helicobacter pylori ( Hp ) who underwent a 14-d Hp eradication therapy with or without consumption of a multi-strain probiotic intervention. 24 Hp eradication therapy consisted of a course of two antibiotics, amoxicillin (beta-lactam) and clarithromycin (macrolide), and a proton pump inhibitor (PPI, pantoprazole). Subjects were randomized toreceive either a fermented milk product (‘Test product’) with probiotics (N = 68, ‘Test’ group) or the control, an acidified but non-fermented milk product (N = 68, ‘Control’ group), during the course of the 2-week Hp therapy and 2 weeks afterward (for a total of 4 weeks), as has been previously described 24 ( Figure 1 ).…”

“… 24 Hp eradication therapy consisted of a course of two antibiotics, amoxicillin (beta-lactam) and clarithromycin (macrolide), and a proton pump inhibitor (PPI, pantoprazole). Subjects were randomized toreceive either a fermented milk product (‘Test product’) with probiotics (N = 68, ‘Test’ group) or the control, an acidified but non-fermented milk product (N = 68, ‘Control’ group), during the course of the 2-week Hp therapy and 2 weeks afterward (for a total of 4 weeks), as has been previously described 24 ( Figure 1 ). No significant difference that could impact the evaluation of product effect was observed between groups for major known confounding factors of gut microbiota such as age, sex, BMI, physical activity, dietary intake (including dietary fiber or alcohol), and smoking habits (Table S1).…”

“…This study showed that the fermented milk product induced a faster recovery (beta-diversity) of global gut microbiota composition characterized by 16S rRNA gene sequencing. 24 In this study, we extended this research using WMS with the goal to gain functional and mechanistic insights into the effects of the fermented milk product and the contribution of the individual strains on the ecological and functional characteristics of gut microbiome recovery.…”

The Probiotic Lactobacillus paracasei Ameliorates Diarrhea Cause by Escherichia coli O8via Gut Microbiota Modulation1

“…Abundant Roseburia can increase the gut SCFA content. SCFAs are metabolites that could potentially treat diarrhea ( 58 , 59 ). Other bacteria such as Akkermansia and Blautia ( 60 ) can alleviate damage to the intestinal barrier damage caused by ulcerative colitis (UC) and inhibit the inflammatory response.…”