Fecal Microbiota Different Between Patients With Melanoma, Controls

Fecal microbiota profiles were significantly different between patients with melanoma and controls, and between patients with early-stage and late-stage melanoma, according to study results published in JAMA Dermatology. Prospective analyses of the gut microbiome and changes that happen with disease progression might target future microbial intervention goals, the authors suggested.

The gut microbiome adjusts the immune system and responses to immunotherapy in patients with late-stage melanoma. New evidence suggests that the gut microbiome might influence the start of cancer, disease progression, drug toxicity, and treatment response. A link between the presence of specific microbes in the gut and immunotherapy response has been shown, but only partial data exists. It isn’t known whether fecal microbiota profiles are different between healthy people and those with melanoma, or if they differ among patients with different stages of melanoma.

Researchers aimed to characterize and compare gut microbiota profiles between healthy volunteers and patients with melanoma, and between patients with early-stage and late-stage melanoma, in hopes that they might uncover factors linked with disease progression.

This study took place at an academic comprehensive cancer center as a single-site case-controlled study. Fecal samples were obtained from systemic treatment–naïve patients with stage I to IV melanoma from June 1, 2021, to January 31, 2022. Disease recurrence was explored through patient follow up until November 30, 2021.

Then, fecal microbiota was profiled by 165 ribosomal RNA sequencing, and clinical and pathologic characteristics, treatment, and disease recurrence were obtained from electronic medical records. Profiles of fecal microbiome diversity, taxonomy, and inferred functionality were compared between groups.

The total number of enrolled participants were 228 (126 men [55.3%]; median age, 59 [range, 21-90] years), including 49 volunteers without melanoma, 38 patients with early-stage melanoma (29 with stage I or melanoma in situ and 9 with stage II), and 141 with late-stage melanoma (66 with stage III and 75 with stage IV).

Community differences were seen between patients with melanoma and volunteers. Patients with melanoma had a higher relative abundance of Fusobacterium compared with controls on univariate analysis (0.19% vs 0.003%; P < .001), but this link was attenuated when adjusted for covariates (log2 fold change of 5.18 vs controls; P = .09). Microbiomes were specific between patients with early-stage and late-stage melanoma.

Early-stage melanoma possessed a higher alpha diversity (median Inverse Simpson Index, 14.6 [IQR, 9.8-23.0] vs 10.8 [IQR, 7.2-16.8]; P = .003), and a higher abundance of the genus Roseburia on univariate analysis (2.4% vs 1.2%; P < .001) but statistical significance was lost with covariate adjustment (log2 fold change of 0.86 vs controls; P = .13).

“Interestingly, we identified the genus Fusobacterium to be differentially enriched among patients with melanoma compared with controls on initial univariate analysis,” said the researchers.

Fusobacterium has been found to be enriched in porcine melanoma tumor tissue and the fecal microbiomes of pigs with melanoma. The researchers and others have shown that gut microbiota diversity is linked with improved outcomes in patients with metastatic melanoma receiving immunotherapy.

Observed community-level differences, paired with lower abundance of well-characterized gut commensals in patients with melanoma, like Roseburia and Ruminococcus, indicate compromised balance or dysbiosis within the gut microbiome across melanoma initiation and progression, though this hypothesis necessitates continued follow-up.

Future studies should analyze the link between Fusobacterium in the skin and gut with tumor progression and treatment response and toxicity, the authors wrote.

This study contains some limitations. While the researchers were able to enroll a large number of patients with late-stage melanoma, the limited sample size of other subcohorts among participants with early-stage melanoma and controls came before thorough comparisons among these groups.

The findings of this study suggest that gut dysbiosis might be associated with melanomagenesis and disease progression.

“Further investigation is needed to confirm these findings and determine whether modifying the gut microbiome could influence melanoma development and progression,” concluded the authors.

Reference

Witt RG, Cass SH, Tran T, et al. Gut microbiome in patients with early-stage and late-stage melanoma. JAMA Dermatol. Published online August 30, 2023. doi:10.1001/jamadermatol.2023.2955