Distinct mucosa-associated microbiota signatures and dysbiosis in Peutz-Jeghers syndrome polyps versus paired normal mucosa.

BACKGROUND

Peutz-Jeghers syndrome (PJS) is an STK11/LKB1-mutated autosomal dominant disorder with gastrointestinal hamartomatous polyps and elevated cancer risk, but the role of mucosa-associated microbiota in PJS polyp pathogenesis remains unclear.

AIM: To investigate the mucosal microbial signatures, dysbiosis characteristics, and potential biomarkers in PJS polyps versus paired normal small intestinal mucosa.

METHODS

A paired-sample design was adopted, enrolling 44 genetically confirmed PJS patients. Mucosa-associated microbiota was profiled via 5R 16S rRNA gene sequencing. Statistical analyses included Wilcoxon rank-sum test, ANOSIM, Spearman's correlation, and random forest modeling.

RESULTS

Alpha diversity (Observed species, Chao1, Shannon) was markedly reduced in polyps (all P < 0.001), while Simpson index increased (P < 0.001). Beta diversity differed significantly between groups (ANOSIM, R = 0.0667, P = 0.002). Polyps were enriched in Pseudomonadota (70.00% vs. 49.51%, P < 0.001) and depleted in Bacillota, Bacteroidota (both P < 0.001). Microbial dysbiosis index (MDI) was higher in polyps (P < 0.001). A 9-genera random forest model achieved AUC = 0.897. Escherichia-Shigella correlated with polyp number (P < 0.05), and Enterococcus correlated with CA72-4 levels (P < 0.05).

CONCLUSION

PJS polyps exhibit significant mucosal microbial dysbiosis, which may serve as potential biomarkers and therapeutic targets for PJS.