Gut Microbiome Patterns May Help Explain Fatigue and Pain During Melanoma Immunotherapy

How Gut Health May Affect Immunotherapy Symptoms

Researchers presenting at the 2026 Oncology Nursing Society Congress reported that the gut microbiome — the collection of bacteria and other microorganisms living in the digestive tract — may influence fatigue, pain and other symptoms experienced by patients with melanoma receiving immune checkpoint inhibitors (ICIs).

The findings came from a pilot study led by Gee Su Yang, PhD, RN, FAAN, of the University of Connecticut School of Nursing, who examined whether gut bacteria patterns were linked to psychoneurological symptoms in patients treated with immunotherapy.

Psychoneurological symptoms refer to symptoms that affect both the brain and nervous system. These can include fatigue, pain, sleep problems, depression, anxiety and difficulty thinking or concentrating.

ICIs are a type of immunotherapy that help the immune system recognize and attack cancer cells. They have significantly improved outcomes for many patients with advanced melanoma, a serious form of skin cancer. However, these treatments can also trigger immune-related side effects that affect daily quality of life.

“The onset of immune-related adverse events can cause or worsen symptoms, including cognitive impairment, sleep disturbance, fatigue, depressive symptoms and pain,” Yang explained during her presentation.

Cognitive impairment refers to problems with memory, concentration or thinking clearly.

Researchers refer to these symptoms collectively as psychoneurological symptoms because they involve both physical and mental health effects.

Fatigue Worsened During the First Months of Treatment

The study followed 15 patients with melanoma who were beginning ICI treatment between March 2023 and December 2024. Participants completed symptom surveys before treatment and again 12 weeks later. Researchers also analyzed stool samples to better understand changes in gut bacteria over time.

Among the symptoms studied, fatigue became worse during the first 3 months of immunotherapy, while pain, sleep disturbances, depression and cognitive symptoms remained relatively stable.

“Fatigue is the most common and disruptive symptom of immune checkpoint inhibitors,” Yang said.

She emphasized the importance of regular symptom monitoring and supportive care strategies to help patients maintain quality of life during treatment.

Certain Gut Bacteria Were Linked to Fatigue and Pain

Although researchers did not observe major overall changes in gut microbiome diversity — meaning the variety of bacteria present in the gut — during treatment, they identified specific bacteria associated with symptom severity.

Some types of gut bacteria, including Oscillibacter — a bacteria linked to inflammation regulation — and Tannerellaceae, a family of bacteria involved in immune system activity, were associated with lower levels of fatigue or pain. Other bacteria, including Lactobacillus and Limosilactobacillus, were associated with higher symptom levels.

The study also found that gut microbiome composition differed based on age and sex, which Yang said may be influenced by hormonal and immune system differences.

Additionally, researchers observed a decrease in Blautia, a bacterial genus that has drawn interest for its potential anti-inflammatory properties. Anti-inflammatory effects may help reduce harmful immune system activity that contributes to symptoms or disease.

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

Metabolic disorders are conditions that affect how the body processes energy and nutrients.

What the Findings Could Mean for Patients

Although the study was small and conducted at a single institution, the findings suggest the gut microbiome could eventually become an important part of symptom management during immunotherapy.

Yang said future supportive care approaches may include dietary counseling or microbiome-targeted interventions designed to reduce symptom burden and improve treatment experiences.

Microbiome-targeted interventions are treatments or lifestyle approaches aimed at improving the balance of healthy bacteria in the gut. These could include dietary changes, probiotics or other therapies in the future.

“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.

Psychosocial support refers to emotional, mental health and social support that helps patients cope with the challenges of cancer and treatment.

Researchers plan to continue studying how diet, genetics and the microbiome interact during immunotherapy treatment. The long-term goal is to better understand whether gut health could become a modifiable factor in helping patients manage symptoms during cancer care.

References

1. “A Pilot Study of the Gut Microbiome and Psychoneurological Symptoms in Melanoma Patients Receiving Immune Checkpoint Inhibitors” by Dr. Gee Su Yang, presented at the 2026 Oncology Nursing Society Congress.