A fermented milk drink containing Lactobacillus casei strain Shirota modulates the esophageal microbiome composition in Barrett's esophagus.

Esophageal adenocarcinoma and its precursor, Barrett's esophagus (BE), are associated with a pro-inflammatory, Gram-negative-dominated esophageal microbiome. In a single-arm pilot study, 23 patients with BE consumed a fermented milk drink containing Lactobacillus casei strain Shirota (LcS) twice daily for 4 weeks, based on the hypothesis that this intervention could shift the microbiome toward a more beneficial Gram-positive profile. Post-intervention, metaplastic columnar epithelium showed a significant increase in Gram-positive Firmicutes (p < 0.01) without changes in overall Eubacterial abundance. DNA-based analyses demonstrated a higher Gram-positive to Gram-negative ratio, with Proteobacteria decreasing from 74% to 52% and Firmicutes increasing from 20% to 31%, including enrichment of Lactobacillus. Microbial diversity increased markedly (p = 9.98 × 10-7) in squamous and metaplastic epithelium. Notably, BE-associated taxa Prevotella and Haemophilus also increased in both tissue types. Overall, the intervention shifted the esophageal microbiome toward a more Gram-positive and diverse composition, while highlighting complex ecological effects warranting further investigation.