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: [email protected].

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