Gut Microbiome and Psychoneurological Symptoms Among Patients With Colorectal Cancer and Their Caregivers: A Pilot Study.

Survivorship in colorectal cancer (CRC) is often accompanied by co-occurring psychoneurological symptoms (PNS, e.g., fatigue, depression, pain), which negatively affect quality of life. Caregivers of individuals with CRC also experience PNS due to caregiving burdens, amplifying distress across the dyad. PNS may be influenced by the activity of the gut microbes. The purpose of this pilot study was to examine gut microbiome diversity and composition, and their association with PNS in CRC patients and their caregivers. Baseline data from a technology-based dyadic intervention were included in this analysis. Eleven patients and eight caregivers provided stool samples and completed PROMIS measures of PNS at baseline. Gut microbiome profiles were assessed using 16S rRNA gene sequencing. Alpha and beta diversity metrics and differential abundance analyses were used to characterize the gut microbiome and examine its associations with PNS. Patients exhibited significantly lower microbial alpha diversity than caregivers in the full sample ( = 0.033). Dyadic comparisons identified 92 differentially abundant taxa, with patients showing depletion of short-chain fatty acid-producing taxa and enrichment of opportunistic taxa. Microbiome-symptom models revealed significant interactions by group (patient vs. caregiver) and taxa-level effects, with patients showing stronger positive associations between microbial alterations and higher PNS severity. CRC patients actively on chemotherapy demonstrated reduced diversity and depletion of beneficial taxa that may contribute to heightened PNS. Caregivers, despite healthier profiles, reported substantial symptom burden that were linked to gut microbiome features, highlighting dyadic interdependence and the potential for microbiome-targeted, dyadic interventions in survivorship care.