Probiotic supplement attenuates chemotherapy-related cognitive impairment in patients with breast cancer: a randomised, double-blind, and placebo-controlled trial
Probiotic supplement attenuates chemotherapy-related cognitive impairment in patients with breast cancer: a randomised, double-blind, and placebo-controlled trial
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益生菌补充剂可减轻乳腺癌患者化疗相关的认知障碍：一项随机、双盲、安慰剂对照试验
DOI：
10.1016/j.ejca.2021.11.006
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发表时间：
2022-01-01
影响因子：
8.4
通讯作者：
Tong, Jianbin
中科院分区：
文献类型：
--
作者：
Zhang Juan;Jie Chen;Tong, Jianbin
背景资料：化疗相关认知功能障碍（CRCI）在癌症患者中非常普遍，与不良结局和生活质量相关。迄今为止，CRCI的管理仍然是一个临床挑战。在此，我们的目的是确定益生菌对CRCI发展和潜在mechanism.Methods的预防作用：我们进行了一项随机，双盲和安慰剂对照试验（ChiCTRINQ-17014181）的159例乳腺癌患者，并进一步研究了在临床前设置的潜在机制。从2018年到2019年，对需要辅助化疗的乳腺癌（I-III期）患者进行了筛选、入组，并在化疗期间随机分配接受益生菌或安慰剂（3粒胶囊，每日2次）。他们的认知，焦虑和抑郁症进行了评估与完善的测定;他们的血浆生物标志物，代谢物和粪便微生物群组成进行了测量。结果：益生菌能显著降低CRCI的发生率，改善大鼠的整体认知功能，改变肠道微生物组成，调节血浆中9种代谢物的变化。在这些代谢产物中，对薄荷-1，8-二烯-7-醇、亚油酸肉碱和1-氨基环丙烷-1-羧酸与CRCI的发生呈负相关。此外，益生菌补充剂增加大鼠的血浆p-薄荷-1，8-二烯-7-醇。外源性p-Mentha-1，8-dien-7-ol可显著减轻化疗诱导的大鼠海马长时程增强功能障碍、突触损伤、氧化应激和胶质细胞活化。结论：益生菌补充剂可通过调节血浆代谢产物（包括p-Mentha-1，8-dien-7-ol）来预防乳腺癌患者CRCI的发生。试验注册：中国临床试验注册中心（ChiCTR-INQ-17014181）[http：//www.chiCTR-INQ-17014181] chictr.org.cn/showproj.aspx? projZ24294]。(c)2021爱思唯尔有限公司保留所有权利。
Background: Chemotherapy-related cognitive impairment (CRCI) is highly preva-lent 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 pre-ventive effects of probiotics on CRCI development and underlying mechanisms.Methods: We conducted a randomised, double-blind and placebo-controlled trial (ChiCTRINQ-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-1,8dien-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-1,8dien-7-ol. Trial registration: Chinese Clinical Trial Registry (ChiCTR-INQ-17014181) [http://www. chictr.org.cn/showproj.aspx?projZ24294].(c) 2021 Elsevier Ltd. All rights reserved.