Effects of concurrent Helicobacter pylori infection and small intestinal bacterial overgrowth on the gut microbiota and metabolic profiles: A multi-omics study.

Abstract

This study investigated the synergistic effects of Helicobacter pylori (Hp) infection and small intestinal bacterial overgrowth (SIBO) on the gut microbiota structure and metabolic profiles and elucidate the underlying pathophysiological mechanisms. Forty-two patients with gastrointestinal symptoms were recruited and assigned to group A (Hp+ SIBO+), B (Hp+ SIBO-), C (Hp- SIBO+), or D (Hp- SIBO-) based on their Hp infection and SIBO status. Fecal samples were collected for metagenomic sequencing and untargeted metabolomic analysis. The associations between microbiota and metabolites were evaluated using alpha/beta diversity analysis, differential species screening, metabolite identification, and Procrustes/Spearman correlation analysis. Neither Hp infection nor SIBO significantly altered the alpha or beta diversity of the gut microbiota (both P > 0.05). However, specific shifts in microbial abundance were observed. Specifically, the abundance of short-chain fatty acid-producing bacteria such as Megamonas was significantly decreased in the SIBO+ groups. Metabolomic analysis revealed significant enrichment of inflammatory metabolites (e.g., prostaglandin derivatives) in group A, disordered bile acid conjugates (e.g., chenodeoxycholylisoleucine) and nucleotide metabolism in SIBO+ groups, and abnormal lipid/carbohydrate metabolism pathways in Hp+ groups. Multi-omics integration analysis indicated a strong coupling between the microbial structure and metabolic profiles (Procrustes analysis, P < 0.05). In group A, the abundance of Faecalibacterium and Hominenteromicrobium was negatively correlated with bile acid levels, suggesting impaired bile acid transformation. Hp infection and SIBO might synergistically exacerbate gut ecological and metabolic disorders by reshaping specific microbiota and metabolic networks (enhanced inflammatory response, disrupted bile acid circulation). Their co-occurrence produces additive effects, which could explain the aggravated clinical symptoms. This study provides a theoretical basis for interventions targeting microbiota-metabolite interactions, such as probiotics and bile acid modulators.