PO.PR01.05 · 预防研究
肠-肝轴功能紊乱与乳腺癌患者化疗诱导的恶心和疲劳相关
Perturbations in gut liver axis functions are associated with chemotherapy induced nausea and fatigue in patients with breast cancer
作者与单位 Authors & Affiliations
摘要 Abstract
中文摘要
背景：高达50%的乳腺癌患者经历化疗诱导的恶心（CIN），95%经历疲劳。对其生物学机制的全面理解仍难以捉摸。在此，我们评估了CIN和疲劳与临床及多组学特征的关联，包括化疗前（T1）至化疗后（T2）的血清和粪便代谢物。
方法：即将接受化疗的乳腺癌患者（n=36）在T1和T2使用纪念症状评估量表提供症状评估，并提供粪便和血液样本。患者在T1使用膳食筛查问卷提供膳食摄入数据。描述性和单变量分析评估了共现症状和饮食与T2时CIN和疲劳的关联。使用鸟枪法宏基因组学对肠道微生物组进行测序。对粪便和血清进行靶向代谢组学分析。评估了从T1到T2分类群丰度和代谢物水平的变化与CIN和疲劳的关联。
结果：约64%的患者在T2经历CIN，94%经历疲劳。三种胃肠道症状与CIN和疲劳共现。较高的每日平均钙摄入量（p=0.013）和乳制品摄入量（p=0.035）与CIN相关。己糖基神经酰胺、神经酰胺、磷脂酰胆碱和鞘磷脂的水平与CIN和疲劳显著相关地发生紊乱（p<0.05）。
结论：CIN和疲劳与鞘脂周转通路的紊乱相关，这对肠-肝轴的功能产生负面影响，包括凋亡活性和胆汁酸水平的变化。需要开展验证性研究以支持开发缓解接受化疗的乳腺癌患者CIN和疲劳的干预措施。关键词：乳腺癌；化疗诱导的恶心；疲劳；代谢物；鞘脂
查看英文原文 English abstract
Background: Up to 50% of patients with breast cancer experience chemotherapy-inducednausea (CIN) and 95% experience fatigue. A comprehensive understanding of biological mechanisms remains elusive. Herein, we evaluated the association of CIN and fatigue with clinical and multi-omics features, including serum and stool metabolites before (T1) to after chemotherapy (T2).
Methods: Patients with breast cancer (n=36) who were to receive chemotherapy, provided symptom assessment using the Memorial Symptom Assessment Scale, stool and blood samples at T1 and T2. Patients provided dietary intake data using a Dietary Screener Questionnaire at T1. Descriptive and univariate analyses evaluated associations of co-occurringsymptoms and diet with CIN and fatigue at T2. Gut microbiome was sequenced using shotgun metagenomics. Targeted metabolomics was performed on stool and serum. Shift in the abundance of taxonomic groups and metabolite levels from T1 to T2 were evaluated in association with CIN and fatigue.
Results: Approximately 64% of the patients experienced CIN and 94% experienced fatigue atT2. Three gastrointestinal symptoms co-occurred with CIN and fatigue. Higher daily average intake of calcium (p=0.013) and dairy (p=0.035) were associated with CIN. Levels of hexosylceramides, ceramide, phosphatidylcholine and sphingomyelins were significantly perturbed in association with CIN and fatigue (p<0.05).
Conclusion: CIN and fatigue are associated with perturbation in the sphingolipid turnover pathway, which negatively impacts functions in the gut-liver axis that include apoptosis activity and change in bile acid levels. Confirmatory studies are warranted to support the development of interventions to alleviate CIN and fatigue in patients with breast cancer receiving chemotherapy.Keywords: breast cancer; chemotherapy-induced nausea; fatigue; metabolites; sphingolipids
利益披露 Disclosure
K. P. Singh, None..
B. J. Ernst, None..
S. Dasari, None..
F. Batalini, None..
C. Tofthagen, None..
K. Pituch, None..
L. Chlan, None.