The Impact of Perioperative Opioids on the Gut Estrobolome in Breast Cancer Patients

项目总结/摘要 本申请是为了响应被标识为NOT-CA的特别利益通知（NOSI）而提交的- 21-100. 五分之一接受乳房切除术的阿片类药物初治患者在手术后一年持续使用阿片类药物， 强调阿片类药物使用对乳腺癌妇女的负担。临床前研究表明， 通过细菌移位和炎性细胞因子的释放对肠道微生物组产生不利影响， 这可能会影响继发性效应，如胃肠道疾病，甚至某些疾病的进展， 癌的肠道微生物组也是类固醇激素代谢的场所。特别是肠道远端的细菌 微生物组“重新激活”排泄到胆汁中的结合雌激素，允许重新进入循环。的 负责释放这些生物活性雌激素的微生物组组分被称为“雌激素组”。 雌激素代谢物浓度的增加似乎与肠道微生物多样性密切相关， 雌激素代谢物与血清雌二醇和雌酮的低比例与乳腺癌的风险增加有关。 癌因此，雌激素组可能影响性类固醇和肿瘤抑制剂的全身浓度。 结果。该提案旨在描述围手术期阿片类药物对雌激素受体及其受体的影响。 通过比较围手术期肠道变化， 接受乳腺癌手术的两组患者之间的微生物组：那些接受标准 基于阿片类药物的疼痛管理和接受经验证的、保留阿片类药物的多模式镇痛方案的患者。 将在术前和术后一周收集粪便和血液样本，以确定围手术期是否 阿片样物质给药与肠道微生物组的不利变化有关。特定微生物菌株 将根据抗生素治疗（无、低、高）对与阿片类药物诱导的雌激素组变化相关的 以解释围手术期抗生素的潜在影响。除了为其他国家提供额外的动力外， 外科医生采用类似的阿片类药物保留围手术期方案，描述阿片类药物对肠道的影响 雌激素敏感性乳腺癌妇女的雌激素受体提供了一种新颖的和创新的方法， 制定未来的干预目标。

Project Summary/Abstract This application is being submitted in response to the Notice of Special Interest (NOSI) identified as NOT-CA- 21-100. One in five opioid-naïve patients undergoing mastectomy is a persistent opioid user one year after surgery, highlighting the burden of opioid use in women with breast cancer. Preclinical studies have shown that opioids adversely impact the gut microbiome through bacterial translocation and the release of inflammatory cytokines, which may influence secondary effects such as gastrointestinal disorders and even the progression of certain cancers. The gut microbiome is also the site of steroid hormone metabolism. Specifically, bacteria of the distal gut microbiome "reactivate” conjugated estrogens excreted into bile, allowing for re-entry into circulation. The microbiome component responsible for liberating these biologically active estrogens is termed the “estrobolome.” Increased estrogen metabolite concentration appears to be strongly associated with gut microbial diversity, and a low ratio of estrogen metabolites to serum estradiol and estrone is associated with an increased risk of breast cancer. Therefore, the estrobolome may influence the systemic concentration of sex steroids and oncologic outcome. This proposal seeks to characterize the impact of perioperative opioids on the estrobolome and its metabolites in a diverse cohort of women with breast cancer by comparing perioperative changes in the gut microbiome between two groups of patients undergoing breast cancer surgery: those that receive standard opioid-based pain management and those that receive a validated, opioid-sparing multimodal analgesia regimen. Stool and blood samples will be collected before and one week after surgery to determine whether perioperative opioid administration is associated with adverse changes in the gut microbiome. Specific microbial strains associated with opioid-induced changes in the estrobolome will be stratified by antibiotic receipt (none, low, high) to account for the potential influence of perioperative antibiotics. Aside from an additional impetus for other surgeons to adopt similar opioid-sparing perioperative protocols, characterizing the impact of opioids on the gut estrobolome in women with estrogen-sensitive breast cancer provides a novel and innovative method to inform the development of future targets of intervention.