Adjunctive probiotic therapy sustains symptom relief in gastroesophageal reflux disease through gut microbiome-metabolome remodeling.

The probiotic group exhibited a significantly greater reduction in RDQ scores compared to placebo after 12 weeks of intervention.

• The probiotic group showed a 36.51% reduction in RDQ scores after 12 weeks (P = 0.017) compared with the placebo group.
• 120 GERD patients were randomized: 64 to rabeprazole plus Lihuo (multi-strain probiotic) and 56 to rabeprazole plus placebo.
• The intervention consisted of 8 weeks of rabeprazole with probiotic or placebo, followed by 4 weeks of probiotic or placebo alone.
• The primary outcome was change in the Reflux Disease Questionnaire (RDQ) score.

The probiotic group had a numerically higher endoscopic healing rate compared to the placebo group, though this difference was not statistically significant.

• Endoscopic healing rate was 36.84% in the probiotic group versus 12.50% in the placebo group.
• The difference in endoscopic healing rates did not reach statistical significance (P = 0.365).
• Endoscopic healing was assessed as a secondary outcome alongside Gastrointestinal Symptom Rating Scale scores.

Shotgun metagenomics revealed enrichment of specific beneficial bacterial taxa in the probiotic group.

• Bifidobacterium animalis, Lactiplantibacillus plantarum, and Clostridium sp900540255 were enriched in the probiotic group.
• Bacteroides uniformis and Clostridium Q fessum were reduced in the probiotic group.
• Multi-omics profiling included shotgun metagenomics, phageome analysis, and untargeted/targeted metabolomics.

Metabolomics analysis revealed increased levels of several bioactive metabolites in the probiotic group.

• Levels of γ-aminobutyric acid (GABA), succinate, citrulline, and short-chain fatty acids were increased in the probiotic group.
• Notable microbe-metabolite correlations were identified, including Bifidobacterium animalis–γ-aminobutyric acid and Bacteroides fragilis–succinate (r ≥ 0.30, P < 0.01).
• Both untargeted and targeted metabolomics approaches were used.

Long-term PPI use in GERD causes dysbiosis, gastrointestinal side effects, and symptom relapse after discontinuation.

• PPIs are described as standard therapy for GERD but are associated with gut microbiome disruption.
• Symptom relapse after PPI discontinuation is identified as a clinical problem motivating the investigation of adjunctive probiotic therapy.
• This background rationale motivated the study design with a post-PPI probiotic-only phase of 4 weeks.

The study employed a randomized, double-blind, placebo-controlled trial design with multi-omics profiling as part of its methodology.

• 120 GERD patients were randomized to receive rabeprazole with Lihuo (n = 64) or placebo (n = 56) for 8 weeks, followed by 4 weeks of probiotic or placebo alone.
• Secondary outcomes included Gastrointestinal Symptom Rating Scale, endoscopic healing, and multi-omics profiling.
• Multi-omics profiling encompassed shotgun metagenomics, phageome analysis, and untargeted/targeted metabolomics.
• The trial is registered with the Chinese Clinical Trial Registry as ChiCTR2000038409.