A Multi-Omics Study of the Effect and Mechanisms of Acupuncture on Psychoneurological Symptoms Among Breast Cancer Survivors

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ABSTRACT A large proportion of breast cancer survivors—24% to 68% of them—report co-occurring psychoneurological (PN) symptoms or the PN symptom cluster (defined as a cluster of pain, fatigue, and sleep disturbance) during and after cancer treatment. Acupuncture is a safe and holistic treatment known to relieve cancer-related symptoms, including PN symptoms. However, its role and mechanism in treating multiple PN symptoms simultaneously remains unclear. Metabolomics can reveal systematic metabolic changes and time-effect relationships between an intervention and the targeted disease. Metabolomic studies suggest that the tryptophan (Trp)–kynurenine (Kyn) metabolic pathway plays a critical role in PN symptoms among cancer survivors. It remains unknown whether the effect of acupuncture on PN symptoms is associated with regulation of the inflammation-induced activation of the Trp-Kyn pathway or is associated with other novel pathways. This R21’s innovative approach to these outstanding questions involves performing an integrated analysis of breast cancer survivors’ serum and fecal metabolome and microbiome before and after an acupuncture intervention. The goal is to understand the effect and mechanism of acupuncture in treating the PN symptom cluster among breast cancer survivors. The specific aims are: (1) to evaluate whether a 5-week acupuncture intervention decreases the severity of the PN symptom cluster (a composite score of pain, fatigue, and sleep disturbance), as well as each of the 3 individual PN symptoms, among breast cancer survivors; (2) to determine whether the hypothesized decrease in the severity of the PN symptom cluster and each PN symptom following acupuncture is associated with changes in targeted Trp-Kyn pathway metabolites; and (3) to explore associations between changes in untargeted biomarkers in the serum and fecal metabolome and gut microbiome and the changes in the PN symptom cluster and each PN symptom. We hypothesize that acupuncture will reduce the PN symptom cluster through the Trp-Kyn metabolomic pathway and will also influence and produce other beneficial changes in the metabolome and microbiome. This integration of large-scale metabolomics and microbiome markers with PN symptom phenotypes will advance a mechanistic understanding of acupuncture and identify novel biomarkers that could be used in future studies of personalized acupuncture approaches to symptom management and relief among breast cancer survivors.