Gut Microbiome in Patients With Early-Stage and Late-Stage Melanoma

JAMA Dermatology
Open Access

Clinical Summary

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What was studied

Single-site case-control study using 16S rRNA sequencing to compare fecal microbiota of healthy volunteers (n=49) with systemic treatment–naive melanoma patients across stages I–IV (n=179), and to contrast early- vs late-stage microbiomes; stage III patients were followed for recurrence through November 30, 2021.

Key findings

Microbiome community profiles differed between melanoma and controls (PERMANOVA R2=0.015, F=3.42, P<2e-16); unadjusted Fusobacterium was higher in melanoma (0.19% vs 0.003%; P<.001) but was not significant after covariate adjustment (log2 fold change 5.18; P=.09). Early-stage melanoma showed higher alpha diversity than late-stage (Inverse Simpson 14.6 [IQR 9.8–23.0] vs 10.8 [7.2–16.8]; P=.003), and in the stage III adjuvant cohort recurrence occurred in 30.3%, with α-diversity differing by recurrence (P=.008) but no microbial taxa predicting recurrence on adjusted analyses.

Study limitations

Single-site case-control design with controls sampled in 2021–2022 vs cases in 2015–2019. Functional pathways were inferred from 16S rRNA data rather than directly measured.

Clinical implications

Gut microbiota profiles differ between controls and melanoma and between early- and late-stage disease, but specific taxonomic signals attenuate after adjustment and did not predict adjuvant recurrence. Treat these findings as hypothesis-generating; they do not support microbiome-guided clinical decisions at this time.