Probiotic supplement attenuates chemotherapy-related cognitive impairment in patients with breast cancer: a randomised, double-blind, and placebo-controlled trial. (January 2022)

• Record Type: Journal Article
• Authors: Juan, Zhang; Chen, Jie; Ding, Boni; Yongping, Liang; Liu, Kai; Wang, Ling; Le, Yuan; Liao, Qin; Shi, Jingcheng; Huang, Jufang; Wu, Yuhui; Ma, Daqing; Ouyang, Wen; Tong, Jianbin
• Is Part Of: European journal of cancer. Volume 161(2022)
• Page Start: 10
• Page End: 22
• Publication Date: 2022-01
• Subjects: Chemotherapy-related cognitive impairment (CRCI) -- Breast cancer -- p-Mentha-1, 8-dien-7-ol -- Probiotics; Cancer -- Periodicals; Neoplasms -- Periodicals; Cancer -- Périodiques; Cancer; Tumors; Electronic journals; Periodicals; Electronic journals; 616.994
• DOI: 10.1016/j.ejca.2021.11.006
• Languages: English
• ISSNs: 0959-8049

Abstract

Abstract: Background: Chemotherapy-related cognitive impairment (CRCI) is highly prevalent in patients with cancer and is associated with poor outcomes and quality of life. To date, the management of CRCI remains a clinical challenge. Herein, we aim to determine the preventive effects of probiotics on CRCI development and underlying mechanisms. Methods: We conducted a randomised, double-blind and placebo-controlled trial (ChiCTR-INQ-17014181) of 159 patients with breast cancer and further investigated the underlying mechanism in a pre-clinical setting. From 2018 to 2019, patients with breast cancer (Stage I-III) who needed adjuvant chemotherapy were screened, enrolled and randomly assigned to receive either probiotics or placebo (three capsules, twice/day) during chemotherapy. Their cognition, anxiety and depression were assessed with well-established assays; their plasma biomarkers, metabolites and faecal microbiota compositions were measured. In addition, the systemic effects of the metabolites found in the clinical trial on long-term potentiation, synapse injury, oxidative stress and glial activation were assessed in rats. Results: Probiotics supplement significantly decreased the incidence of CRCI, improved the allover cognitive functions, changed the gut microbial composition and modulated nine plasma metabolite changes. Among these metabolites, p-Mentha-1, 8-dien-7-ol, Linoelaidyl carnitine and 1-aminocyclopropane-1-carboxylic acid were negatively correlated with the occurrence of CRCI. Furthermore, probiotics supplement increased plasma p-Mentha-1, 8-dien-7-ol in rats. Administration of exogenous p-Mentha-1, 8-dien-7-ol significantly alleviated chemotherapy-induced long-term potentiation impairment, synapse injury, oxidative stress and glial activation in the hippocampus of rats. Conclusion: Our data indicated that probiotics supplement prevents the occurrence of CRCI in patients with breast cancer via modulating plasma metabolites, including p-Mentha-1, 8-dien-7-ol. Trial registration: Chinese Clinical Trial Registry (ChiCTR-INQ-17014181) [http://www.chictr.org.cn/showproj.aspx?proj=24294 ]. Highlights: Probiotics prevented chemotherapy-related cognitive impairment in patients. Probiotics supplement mitigated chemotherapy-induced metabolic abnormalities. p-Mentha-1, 8-dien-7-ol(i.p.) alleviated CRCI-related brain impairment in rats.