Gut Microbiome Patterns Influence Fatigue and Pain in Melanoma Patients Receiving ICIs

Pilot study examines gut microbiome and psychoneurological symptoms

A pilot study presented at the 2026 Oncology Nursing Society Congress explored how the gut microbiome may influence psychoneurological symptoms among patients with melanoma receiving immune checkpoint inhibitors (ICIs), highlighting a potential future role for microbiome-targeted symptom management strategies in oncology nursing care.

Gee Su Yang, PhD, RN, FAAN, of the University of Connecticut School of Nursing, presented findings from the study, titled “A Pilot Study of the Gut Microbiome and Psychoneurological Symptoms in Melanoma Patients Receiving Immune Checkpoint Inhibitors,” during a presentation at the meeting.

ICIs have transformed treatment for advanced cancers, including melanoma, by improving survival and reducing recurrence. However, Yang explained that immune-related adverse events (irAEs) associated with these therapies can contribute to symptom burdens that are often underrecognized in clinical settings.

“The onset of immune-related adverse events can cause or worsen symptoms, including cognitive impairment, sleep disturbance, fatigue, depressive symptoms and pain, collectively referred to as psychoneurological symptoms,” Yang said during the presentation.

The longitudinal prospective pilot study enrolled 15 patients with melanoma initiating ICI therapy at the University Cancer Center between March 2023 and December 2024. Participants completed symptom assessments at baseline and again 12 weeks after treatment initiation. Researchers also analyzed stool samples using 16S rRNA sequencing to characterize gut microbiome composition.

Fatigue emerged as an early and persistent symptom during ICI therapy

The study found that fatigue worsened over the first 3 months of treatment, while depression, pain, cognitive impairment and sleep disturbances remained relatively stable but clinically meaningful throughout the study period.

“Fatigue is the most common and disruptive symptom of immune checkpoint inhibitors,” Yang said. “Fatigue resulted [as] an early and persistent symptom during immune checkpoint inhibitor treatment, emphasizing the need for routine assessment and tailored management strategies.”

Specific microbial taxa were linked to pain and fatigue severity

Although overall microbiome richness and diversity did not significantly change over time, investigators identified associations between specific microbial taxa and symptom severity. Oscillibacter and Tannerellaceae were associated with lower symptom severity in some domains, whereas Lactobacillus and Limosilactobacillus were associated with increased fatigue and pain measures.

Researchers also observed that microbiome composition varied according to age and sex. Yang noted that biologic sex differences may influence the gut microbiome through hormonal and immune-related mechanisms.

Additionally, the bacterial genus Blautia decreased over the course of treatment. Yang explained that Blautia has attracted increasing research attention because of its potential anti-inflammatory and metabolic regulatory effects.

“Blautia has gained significant attention due to its role in reducing inflammation, metabolic disorders and its antibacterial effect against certain microorganisms,” Yang said.

Age and sex influenced gut microbiome variation

Although the study was limited by its small sample size and single-institution design, the findings suggest that gut microbiome patterns may contribute to symptom experiences during immunotherapy treatment.

Yang emphasized that oncology nurses are well positioned to integrate emerging microbiome evidence into supportive care strategies for patients receiving ICIs.

“Nurses can play an important role by implementing evidence-based interventions such as physical activity counseling and psychosocial support to mitigate fatigue and maintain quality of life,” Yang said.

Findings support future nurse-led symptom research

Yang added that future interventions could include dietary counseling or microbiome-targeted approaches aimed at optimizing immunotherapy outcomes and symptom management.

The investigators plan to expand the research by integrating genomic and dietary data in future studies. Yang concluded that the pilot findings underscore opportunities for nurse-led research examining gut health as a modifiable factor in symptom management among patients receiving immunotherapy.

References

1. Yang GS. A Pilot Study of the Gut Microbiome and Psychoneurological Symptoms in Melanoma Patients Receiving Immune Checkpoint Inhibitors. Presented at: Oncology Nursing Society Congress; 2026; Washington, DC.