Gut microbiome may help predict melanoma recurrence after immunotherapy

Could the bacteria living in the gut help determine whether melanoma returns after treatment? The answer may be yes, according to new research published April 17, 2026, in Cell. Investigators found that specific gut microbiome patterns were linked to recurrence-free survival in patients with high-risk melanoma receiving immune checkpoint blockade (ICB), raising the possibility that stool-based biomarkers could one day help personalize cancer treatment decisions.

“Our study provides strong evidence that the gut microbiome is a reliable predictive marker for melanoma immunotherapy treatment outcomes,” says lead author Jiyoung Ahn, Ph.D., professor of population health at NYU Grossman School of Medicine and associate director for population science at NYU Perlmutter Cancer Center in New York City. “This may serve as a potential tool to guide patient stratification and improve immunotherapy outcomes.”

Melanoma is one of the most aggressive forms of skin cancer. People with high-risk melanoma often have surgery to remove the cancer. After surgery, they may be treated with adjuvant immunotherapy — specifically immune checkpoint inhibitors — to lower the chance that the cancer comes back. However, up to 40% of patients still experience recurrence despite treatment, highlighting the need for better tools to predict who is most likely to benefit.

To address this gap, researchers set out to determine whether the gut microbiome before treatment could help predict which patients are more likely to have their cancer return. In the study, Ahn and colleagues analyzed stool samples from 674 patients enrolled in the CheckMate 915 trial, which compared Opdivo (nivolumab) plus Yervoy (ipilimumab) versus Opdivo alone after melanoma resection.

Using genetic sequencing, the researchers identified several bacterial groups associated with recurrence-free survival, including Eubacterium, Ruminococcus, Firmicutes and Clostridium. These bacteria have previously been linked to immune activity and immunotherapy response in metastatic melanoma, but this is one of the first studies to evaluate their role in the adjuvant setting.

The predictive performance of microbiome markers was strongest when patients in the validation group had gut microbiome profiles closely matching those in the discovery group. Among individuals with highly similar microbiome composition, recurrence prediction accuracy was high, with area-under-the-curve values ranging from 0.78 to 0.94 across geographic regions.

The study also found that the gut microbiome remained relatively stable during immunotherapy treatment, suggesting that microbiome-related treatment effects may persist throughout therapy. According to the authors, this stability may support future interventions aimed at modifying the microbiome to improve outcomes.

The findings build on growing evidence that the microbiome plays an important role in cancer immunotherapy response. Prior studies have shown that fecal microbiota transplantation and dietary interventions, such as high-fiber diets, may alter the gut microbiome in ways that enhance immune activity and improve responses to checkpoint inhibitors.

In the current analysis, the researchers also observed links between recurrence-associated bacteria and carbohydrate metabolism pathways in the microbiome. Some of these pathways have previously been associated with cancer treatment response. The authors noted that dietary factors may influence these bacterial populations, potentially opening the door to microbiome-targeted interventions.

One of the more challenging aspects of microbiome research has been geographic variability. Previous studies have found that gut microbiome composition can differ substantially between populations and regions, complicating efforts to identify universal biomarkers. In this study, the researchers addressed that issue by matching patients with similar microbiome profiles across regions, which improved predictive accuracy.

Although the findings are promising, the authors acknowledged several limitations, including the need for larger and more diverse datasets before microbiome-based prediction tools can be broadly implemented in clinical practice.

Still, the study offers an important step toward more personalized melanoma care. As immunotherapy is increasingly used in earlier-stage disease, tools to identify which patients are most likely to benefit are becoming more important. The researchers suggest that the gut microbiome could eventually serve as a clinically actionable biomarker to help guide treatment decisions, reduce recurrence risk, and improve outcomes for patients with high-risk melanoma.