Lactobacillus casei Shirota intervention modulates the esophageal microbiome composition in Barrett’s esophagus

Objective: Esophageal adenocarcinoma (EAC) and its precursor, Barrett's esophagus (BE), are associated with a pro-inflammatory, Gram-negative-dominated esophageal microbiome. We investigated whether Lactobacillus casei Shirota (LcS) consumption could shift the microbiome towards a more Gram-positive profile in BE patients. Design: In a single-arm intervention study, 23 BE patients used LcS twice daily for 4 weeks. Endoscopic biopsies from normal squamous epithelium (NSE) and metaplastic columnar epithelium (MCE), both before and after LcS-intervention were analyzed using 16S rRNA gene sequencing for microbiome composition, digital droplet PCR for Gram-positive to negative ratio, and fluorescence in situ hybridization to visualize Eubacteria and Firmicutes. Results: LcS intervention increased Gram-positive Firmicutes in MCE in situ (p<0.01) while the overall abundance of Eubacteria was unaffected. Analysis at DNA level showed an increased Gram-positive to Gram-negative ratio post-LcS. The abundance of Gram-negative Proteobacteria lowered from 74% pre-LcS to 52% post-LcS, while the abundance of Gram-positive Firmicutes, including the genus Lactobacillus, increased from 20% pre-LcS to 31% post-LcS. Overall microbiota diversity significantly increased post-LcS (p=9.9778e-07). LcS intervention also resulted in an increased abundance in the BE associated taxa Prevotella and Haemophilus in both NSE as MCE. Conclusion: LcS consumption significantly altered the esophageal microbiome in BE patients, increasing Gram-positive taxa and overall diversity. These findings underscore the potential of probiotic-based therapeutic strategies aimed at EAC prevention. However, the concurrent rise in BE associated taxa warrants careful consideration and further personalized studies to maximize benefits and minimize unintended consequences for optimal outcomes in BE patients.