Elevated levels of circulating microbial-associated uremic toxins are associated with metastatic duodenopancreatic neuroendocrine tumors in patients with Multiple Endocrine Neoplasia Type 1.

Summary

In MEN1, circulating microbial-associated uremic toxins (e.g., TMAO, indoxyl sulfate) were elevated in patients with metastatic dpNETs and correlated with microbial peptide signatures in tumor tissue. A multi-marker panel achieved an AUC of 0.94 (67% sensitivity at 95% specificity) in an independent validation cohort, and early increases associated with worse survival in a Men1 model.

Key Findings

• Circulating TMAO, indoxyl sulfate, cresol sulfate, cresol glucuronide, and phenol sulfate were elevated in MEN1 patients with metastatic dpNETs.
• A microbial-associated uremic toxin panel (MUTP) achieved AUC 0.94 (95% CI 0.85–1.00), 67% sensitivity at 95% specificity in an independent validation cohort.
• Tumor proteomic/metabolomic profiles correlated with bacterial peptide signatures (e.g., F. nucleatum, F. prausnitzii, K. pneumoniae) and uremic toxin levels; early toxin increases associated with poorer survival in a Men1 model.

Clinical Implications

A validated uremic toxin panel could help prioritize imaging and intensify follow-up for MEN1 patients at high risk of metastasis, enabling earlier interventions.

Limitations

• Exact cohort sizes and multicenter generalizability are not specified in the abstract
• Causality between microbial signatures and metastasis cannot be inferred from observational data

Future Directions

Prospective, multicenter validation and assessment of clinical utility (e.g., risk-adapted imaging schedules) and mechanistic studies to disentangle microbiome–tumor interactions.