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

Zhang Juan; Jie Chen; Boni Ding; Liang Yongping; Kai Liu; Ling Wang; Yuan Le; Qin Liao; Jingcheng Shi; Jufang Huang; Yuhui Wu; Daqing Ma; Wen Ouyang; Jianbin Tong

doi:10.1016/j.ejca.2021.11.006

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

Eur J Cancer. 2022 Jan:161:10-22. doi: 10.1016/j.ejca.2021.11.006. Epub 2021 Dec 9.

Authors

Zhang Juan¹, Jie Chen², Boni Ding³, Liang Yongping⁴, Kai Liu¹, Ling Wang³, Yuan Le¹, Qin Liao¹, Jingcheng Shi⁵, Jufang Huang⁶, Yuhui Wu⁷, Daqing Ma⁸, Wen Ouyang⁹, Jianbin Tong¹⁰

Affiliations

¹ Department of Anesthesiology, Third Xiangya Hospital, Central South University, Changsha, Hunan, 410013, PR China; Hunan Province Key Laboratory of Brain Homeostasis, Third Xiangya Hospital, Central South University, Changsha, Hunan, 410013, PR China.
² Center for Experimental Medicine, Third Xiangya Hospital, Central South University, Changsha, Hunan, 410013, PR China; Department of Anatomy and Neurobiology, School of Basic Medical Sciences, Central South University, Changsha, Hunan, 410013, PR China.
³ Department of Breast and Thyroid Surgery, Third Xiangya Hospital, Central South University, Changsha, Hunan, 410013, PR China.
⁴ Department of Medical Imaging (Ultrasound), Third Xiangya Hospital, Central South University, Changsha, Hunan, 410013, PR China.
⁵ Department of Epidemiology and Health Statistics, Xiangya School of Public Health, Central South University, Changsha, Hunan, 410078, PR China.
⁶ Department of Anatomy and Neurobiology, School of Basic Medical Sciences, Central South University, Changsha, Hunan, 410013, PR China.
⁷ Department of Breast Surgery, Xiangya Hospital, Central South University, Changsha, Hunan, 410008, PR China.
⁸ Division of Anaesthetics, Pain Medicine and Intensive Care, Department of Surgery and Cancer, Faculty of Medicine, Imperial College London, Chelsea and Westminster Hospital, London, UK.
⁹ Department of Anesthesiology, Third Xiangya Hospital, Central South University, Changsha, Hunan, 410013, PR China; Hunan Province Key Laboratory of Brain Homeostasis, Third Xiangya Hospital, Central South University, Changsha, Hunan, 410013, PR China. Electronic address: ouyangwen133@vip.sina.com.
¹⁰ Department of Anesthesiology, Third Xiangya Hospital, Central South University, Changsha, Hunan, 410013, PR China; Hunan Province Key Laboratory of Brain Homeostasis, Third Xiangya Hospital, Central South University, Changsha, Hunan, 410013, PR China. Electronic address: jianbintong@csu.edu.cn.

PMID: 34896904
DOI: 10.1016/j.ejca.2021.11.006

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].

Keywords: Breast cancer; Chemotherapy-related cognitive impairment (CRCI); Probiotics; p-Mentha-1,8-dien-7-ol.

Publication types

Randomized Controlled Trial
Research Support, Non-U.S. Gov't

MeSH terms

Adult
Breast Neoplasms / complications*
Chemotherapy-Related Cognitive Impairment / drug therapy*
Double-Blind Method
Female
Humans
Middle Aged
Probiotics / pharmacology
Probiotics / therapeutic use*
Prospective Studies
Young Adult

Associated data

ChiCTR/ChiCTR-INQ-17014181