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Original Research| Volume 161, P10-22, January 2022

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

  • Author Footnotes
    1 ZJ and JC contributed equally to this work.
    Zhang Juan
    Footnotes
    1 ZJ and JC contributed equally to this work.
    Affiliations
    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
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  • Author Footnotes
    1 ZJ and JC contributed equally to this work.
    Jie Chen
    Footnotes
    1 ZJ and JC contributed equally to this work.
    Affiliations
    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
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  • Boni Ding
    Affiliations
    Department of Breast and Thyroid Surgery, Third Xiangya Hospital, Central South University, Changsha, Hunan, 410013, PR China
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  • Liang Yongping
    Affiliations
    Department of Medical Imaging (Ultrasound), Third Xiangya Hospital, Central South University, Changsha, Hunan, 410013, PR China
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  • Kai Liu
    Affiliations
    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
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  • Ling Wang
    Affiliations
    Department of Breast and Thyroid Surgery, Third Xiangya Hospital, Central South University, Changsha, Hunan, 410013, PR China
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  • Yuan Le
    Affiliations
    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
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  • Qin Liao
    Affiliations
    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
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  • Jingcheng Shi
    Affiliations
    Department of Epidemiology and Health Statistics, Xiangya School of Public Health, Central South University, Changsha, Hunan, 410078, PR China
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  • Jufang Huang
    Affiliations
    Department of Anatomy and Neurobiology, School of Basic Medical Sciences, Central South University, Changsha, Hunan, 410013, PR China
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  • Yuhui Wu
    Affiliations
    Department of Breast Surgery, Xiangya Hospital, Central South University, Changsha, Hunan, 410008, PR China
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  • Daqing Ma
    Affiliations
    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
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  • Wen Ouyang
    Correspondence
    Corresponding author: Department of Anesthesiology, Third Xiangya Hospital, 138 Tongzipo Road, Yuelu District, Changsha, Hunan, 410013, PR China.
    Affiliations
    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
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  • Jianbin Tong
    Correspondence
    Corresponding author: Department of Anesthesiology, Third Xiangya Hospital, 138 Tongzipo Road, Yuelu District, Changsha, Hunan, 410013, PR China.
    Affiliations
    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
    Search for articles by this author
  • Author Footnotes
    1 ZJ and JC contributed equally to this work.
Published:December 09, 2021DOI:https://doi.org/10.1016/j.ejca.2021.11.006

      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.

      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

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