Acupuncture ameliorates breast cancer-related fatigue by regulating the gut microbiota-gut-brain axis.

Cancer-related fatigue (CRF) is the most common side effect of chemotherapy for breast cancer (BC). Acupuncture treatment has an anti-fatigue effect and can regulate gut microbiota disturbance in fatigue patients. Related studies have shown that the gut microbiota-gut-brain axis is closely related to the occurrence of CRF. In this study, we first investigated the alterations of acupuncture on fatigue-like behavior, gut microbiota, gut inflammation and neuroinflammation response, gut barriers, HPA axis, and serum metabolomics in CRF mice after BC chemotherapy. Then, the correlation analysis of gut microbiota and other indicators was discussed. Our results showed that acupuncture treatment could exert an anti-fatigue effect and ameliorate the gut barrier, gut inflammation, neuroinflammation, and dysfunction of the HPA axis in CRF mice after chemotherapy for BC. 16S rRNA sequencing showed that acupuncture treatment could enhance the abundance of Candidatus Arthromitus, Lactobacillus, and Clostridia_UCG-014_unclassified and decrease the abundances of Escherichia-Shigella, Burkholderia-Caballeronia-Paraburkholderia, and Streptococcus. Serum metabolomics analysis showed that acupuncture treatment could regulate the differential metabolites N-methylnicotinamide, beta-glycerophosphoric acid, geranyl acetoacetate, serotonin and phenylalanine, tyrosine and tryptophan biosynthesis, taurine and hypotaurine, and beta-alanine metabolic pathways. Correlation analysis indicated that there are certain correlations between gut microbiota and gut inflammation, neuroinflammation, gut barrier, HPA axis function and serum metabolites. In conclusion, our findings revealed that the anti-fatigue mechanism of acupuncture treatment may be closely related to the gut microbiota-gut-brain axis. This study also provided a new reference for basic and clinical research on CRF after breast cancer chemotherapy.

The Clinical Observation and Mechanism of Acupuncture on Cancer-Related Fatigue of Breast Cancer Based on "Gut-Brain Axis": Study Protocol for a Randomized Controlled Trial.

Background. Cancer-related fatigue (CRF) is a painful, persistent feeling of physical and cognitive subjective fatigue related to cancer or cancer remedy. The occurrence of CRF may be related to the hypothalamic-pituitary-adrenaline (HPA) axis, inflammatory mediator theory, and gut microbiota. Moreover, acupuncture could play a vital part in the therapy of CRF. The study will evaluate whether acupuncture can improve fatigue symptoms of CRF patients after breast cancer chemotherapy by regulating the gut-brain axis. Methods/design. Seventy patients with CRF will be enrolled in this study, with 35 patients randomly assigned to each group. Blood and feces will be collected at the beginning and end of treatment. Piper fatigue scale, KPS score scale, and quality-of-life scale will be used to observe the changes of fatigue symptoms and life quality of CRF patients and to evaluate the effect of acupuncture on CRF. Then, the method of ELISA will be used to explore the regulatory effect of acupuncture on the HPA axis and inflammatory cytokines. Moreover, based on 16SrDNA, the changes of gut microbiota structure and flora of CRF patients will be observed. Ultimately, the correlation analysis of gut microbiota can be related to inflammatory cytokines, HPA axis, and clinical efficacy evaluation. Discussion. This study will identify the effect and the mechanism of acupuncture therapy in CRF. And it will offer an alternative treatment modality for the treatment of CRF after chemotherapy for breast cancer. Furthermore, it will also provide the clinical and theoretical bases for the extensive application of acupuncture therapy in tumor rehabilitation. Trial Status. Protocol version number and date: V2.0, 6 May 2021. The trial is registered with the Chinese Clinical Trial Registry on 20 June 2021 (trial identifier: ChiCTR2100047510).