Pinpointing Key Features of Gut Dysbiosis in Melanoma

TOPLINE:

Fecal microbiota profiles differ among healthy individuals and patients with melanoma as well as among people with early and late-stage melanoma, suggesting that gut dysbiosis may be a targetable element of melanoma pathogenesis and disease progression.

METHODOLOGY:

The gut microbiome influences response to immunotherapy in late-stage melanoma, but it's unclear whether fecal microbiota profiles differ between healthy individuals and patients with different stages of melanoma.
To find out, investigators compared fecal samples from 49 healthy volunteers, 38 patients with early stage melanoma, and 141 with stage III or IV melanoma; patients were naïve to systemic treatment.
Fecal samples were collected from both the melanoma and control groups, and microbiota profiling was performed by 16S ribosomal RNA sequencing.

TAKEAWAY:

Patients with melanoma had a lower abundance of beneficial gut microbes compared with controls. Microbiome diversity was not significantly different in patients with melanoma compared with controls but was lower in patients with late-stage vs early stage melanoma.
Patients with melanoma had a higher relative abundance of Fusobacterium compared with controls (0.19% vs 0.003%) as well as a lower abundance of Ruminococcus (1.4% vs 1.7%; P = .03). The association with Fusobacterium was attenuated when adjusting for covariates.
Compared with patients with late-stage melanoma, those with early stage disease had a higher abundance of the genus Roseburia, which is associated with gut barrier homeostasis — 2.4% vs 1.2% — but the association was attenuated when adjusting for covariates (P = .13).
The researchers did not identify an association between microbial taxa and disease recurrence among patients with stage III melanoma who received immunotherapy.

IN PRACTICE:

The findings "suggest compromised balance or dysbiosis within the gut microbiome across melanoma initiation and progression" and that "gut dysbiosis may be linked to melanomagenesis [melanoma pathogenesis] and disease progression," the authors concluded, suggesting that future studies explore "whether modifying the gut microbiome could influence melanoma development and progression."

SOURCE:

The work, led by Russell Witt, MD, of the MD Anderson Cancer Center, Houston, Texas, was published online August 30 in JAMA Dermatology.

LIMITATIONS:

The study included a relatively small number of subjects. The analysis did not control for diet, lifestyle, and medication differences between the groups. It's unclear whether gut dysbiosis is a cause or consequence of disease.

DISCLOSURES:

The National Institutes of Health and others funded the work. Investigators reported grants and/or personal fees from many pharmaceutical companies, including Bristol Myers Squibb, Merck, and Novartis. One investigator holds a patent on modifying the microbiome to enhance immunotherapy response.

M. Alexander Otto is a physician assistant with a master’s degree in medical science and a journalism degree from Newhouse. He is an award-winning medical journalist who worked for several major news outlets before joining Medscape. Alex is also an MIT Knight Science Journalism fellow. Email: aotto@mdedge.com.

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