Predictive and Preventive Potential of Preoperative Gut Microbiota in Chronic Postoperative Pain in Breast Cancer Survivors
Predictive and Preventive Potential of Preoperative Gut Microbiota in Chronic Postoperative Pain in Breast Cancer Survivors
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术前肠道微生物群对乳腺癌幸存者慢性术后疼痛的预测和预防潜力
DOI：
10.1213/ane.0000000000005713
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发表时间：
2022-04-01
影响因子：
5.7
通讯作者：
Ke-Xuan Liu
中科院分区：
文献类型：
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作者：
Zhi-Wen Yao;Yang, Xiao;Ke-Xuan Liu
背景：有证据表明肠道微生物群与慢性术后疼痛（CPP）之间存在潜在关系。本研究旨在探讨术前肠道微生物群对乳腺癌幸存者 CPP 的预测和预防潜力。方法：在临床实验中，我们设计了一项巢式病例对照研究，使用 16s rRNA 测序比较有和没有 CPP 的乳腺癌幸存者的术前肠道微生物群。主要结果是术后 3 个月手术区域内或周围有临床意义的疼痛。基于先前确定的乳腺癌幸存者 CPP 危险因素的逻辑预测模型在有差异细菌和无差异细菌的情况下进行了测试，以评估该模型通过添加肠道微生物群信息进行改进的潜力。在动物实验中，将患有和不患有CPP的患者的术前粪便微生物群移植到小鼠体内，并使用幸存神经损伤（SNI）模型来模拟CPP的神经病理性疼痛。评估了机械痛觉过敏以及脊髓小胶质细胞和过氧化物酶体增殖物激活受体-γ（PPAR-γ）标记物的表达。结果：对 66 名 CPP 患者和 66 名匹配对照进行了分析。两组术前肠道微生物群组成在门、科和属水平上存在显着差异。科和属水平的差异肠道微生物群参与后，临床预测模型的辨别力（由受试者工作特征曲线下面积确定）分别提高了 0.039 和 0.099。粪便微生物群移植 (FMT) 后，“CPP 微生物群”受体小鼠表现出显着增加的机械痛觉过敏以及脊髓中 Ppar-γ 和精氨酸酶-1 (Arg-1) 表达的降低。结论：术前肠道微生物群具有预测和预防 CPP 发展的潜力，并通过脊髓中的 PPAR-γ-小胶质细胞通路在其发展中发挥因果作用。因此，可以有针对性地制定乳腺癌幸存者 CPP 的预防策略。
BACKGROUND: Evidence suggests a potential relationship between gut microbiota and chronic postoperative pain (CPP). This study aimed to explore the predictive and preventive potential of preoperative gut microbiota in CPP in breast cancer survivors. METHODS: In the clinical experiments, we designed a nested case-control study to compared preoperative gut microbiota of breast cancer survivors with and without CPP using 16s rRNA sequencing. The primary outcome was clinically meaningful pain in or around the operative area 3 months after surgery. Logistic prediction models based on previously identified risk factors for CPP in breast cancer survivors were tested with and without differential bacteria to evaluate the model’s potential for improvement with the addition of gut microbiota information. In the animal experiments, preoperative fecal microbiota was transplanted from patients with and without CPP to mice, and a spared nerve injury (SNI) model was used to mimic neuropathic pain in CPP. Mechanical hyperalgesia and the expression of markers of spinal microglia and peroxisome proliferator–activated receptor-γ (PPAR-γ) were assessed. RESULTS: Sixty-six CPP patients and 66 matched controls were analyzed. Preoperative gut microbiota composition was significantly different in the 2 groups at phylus, family, and genera levels. The discrimination of the clinical prediction model (determined by area under the receiver operating characteristic curve) improved by 0.039 and 0.099 after the involvement of differential gut microbiota at the family and genus levels, respectively. After fecal microbiota transplantation (FMT), “CPP microbiota” recipient mice exhibited significantly increased mechanical hyperalgesia and decreased expression of Ppar-γ and arginase-1 (Arg-1) in the spinal cord. CONCLUSIONS: Preoperative gut microbiota has the potential to predict and prevent the development of CPP and plays a causal role in its development via the PPAR-γ-microglia pathway in the spinal cord. Thus, it could be targeted to develop a prevention strategy for CPP in breast cancer survivors.