Clinical Summary

• In melanoma patients receiving immune checkpoint inhibitors, fatigue worsened over 12 weeks, while other psychoneurological symptoms remained stable.
• Specific gut microbiome taxa were significantly associated with fatigue and pain severity, indicating a potential biological link.
• Findings suggest microbiome-targeted strategies may help manage symptom burden, though larger studies are needed.

Immune checkpoint inhibitors (ICIs) have improved outcomes in advanced melanoma, but treatment-related adverse effects, including psychoneurological symptoms (PNS), remain a clinical challenge. A pilot longitudinal study from was presented at the 2026 Oncology Nursing Society (ONS) Congress examining associations between gut microbiome composition and PNS in melanoma patients undergoing ICI therapy.

The prospective study enrolled 15 patients initiating ICIs at a university cancer center between March 2023 and December 2024. Participants were assessed at baseline and 12 weeks post-treatment. Psychoneurological symptoms including fatigue, depression, pain, cognitive impairment, and sleep disturbances were measured using validated instruments, while gut microbiome composition was analyzed through fecal 16S rRNA sequencing.

Over the 12-week period, fatigue worsened, whereas depression, pain, cognitive impairment, and sleep disturbances remained stable. No significant changes were observed in overall gut microbiome richness, diversity, or community structure. However, demographic factors, including age and sex, were associated with compositional variation.

Regression analyses identified multiple microbial taxa linked to symptom severity. Fatigue severity was associated with Oscillibacter, the NK4A214 group, and Lactobacillus, while additional associations were observed between Oscillibacter, Limosilactobacillus, and Erysipelotrichaceae with average fatigue levels. Pain severity was associated with Tannerellaceae, Bacteroides, and Acidaminococcus. Pain interference during ICI treatment was linked to Oscillibacter and Limosilactobacillus. All reported associations were statistically significant (P <.05).

These findings highlight fatigue as an early and persistent symptom during ICI therapy and suggest a potential microbiome-mediated mechanism underlying symptom burden. Although overall microbial diversity did not change significantly, the identification of specific taxa associated with symptoms points to more nuanced biological interactions. The associations between gut microbiota and PNS suggest that future interventions could incorporate microbiome-targeted approaches, such as dietary modification or other strategies aimed at altering microbial composition.

However, given the small sample size and pilot design, these findings should be interpreted cautiously. Larger, longitudinal studies are needed to validate these associations and determine causality. Understanding the role of the gut microbiome in symptom development may ultimately inform personalized supportive care strategies for melanoma patients undergoing immunotherapy.

“Fatigue is often an early and persistent symptom during ICI treatment, underscoring the need for routine assessment and tailored management strategies,” the authors noted. They further emphasized that “specific taxa were associated with PNS during ICI treatment, suggesting a potential microbiome-mediated pathway underlying symptom experiences.”

In summary, this pilot study provides preliminary evidence linking gut microbiome composition to psychoneurological symptoms in melanoma patients receiving ICIs. Further research may clarify whether microbiome-based interventions can mitigate symptom burden and improve patient outcomes.

Source:

Yang GS, Hegde U, Guan Z, Maas K, Cong X. A Pilot Study of the Gut Microbiome and Psychoneurological Symptoms in Melanoma Patients Receiving Immune Checkpoint Inhibitors. Presented at the Oncology Nursing Society Annual Congress; May 13-17, 2026. San Antonio, TX.