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

围手术期阿片类药物对乳腺癌患者肠道雌激素的影响

• 批准号: 10752298
• 负责人: Stephen D. Nimer
• 金额: $ 19.19万
• 依托单位: UNIVERSITY OF MIAMI SCHOOL OF MEDICINE
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-07-10 至 2024-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10752298
• 关键词: Absence of pain sensation; Adopted; Antibiotics; Bacteria; Bacterial Translocation; Bile fluid; Blood Vessels; Blood specimen; Body mass index; Breast Cancer Patient; Breast Cancer Risk Factor; Butyrivibrio; Cancer Model; Caring; Circulation; Clinical; Conjugated Estrogens; Data; Dependence; Development; Distal; Distant; Distant Metastasis; Enteral; Estradiol; Estrogens; Estrone; Ethnic Origin; Excretory function; Expression Profiling; Female Breast Carcinoma; Future; Gastrointestinal Diseases; Gastrointestinal tract structure; Glucuronides; Gonadal Steroid Hormones; Hormones; Human; Iatrogenesis; Immunosuppression; In Vitro; Inflammatory; Intervention; Leuconostoc; Link; Malignant Neoplasms; Mastectomy; Menopausal Status; Metabolic; Methods; Operative Surgical Procedures; Opioid; Opioid Analgesics; Outcome; Pain management; Parents; Pathogenicity; Pathway interactions; Patients; Pattern; Perioperative; Population; Postmenopause; Postoperative Period; Premenopause; Procedures; Protocols documentation; Race; Recovery; Regimen; Risk; Sampling; Serum; Site; Sulfate; Surgeon; Time; Woman; behavior influence; beta diversity; breast surgery; cancer cell; cancer surgery; carcinogenesis; cohort; comorbidity; cytokine; dysbiosis; gut bacteria; gut microbiome; hormone metabolism; in vivo; indexing; innovation; interest; lens; malignant breast neoplasm; microbial; microbial signature; microbiome; microbiome components; multimodality; novel; opioid sparing; opioid use; opioid user; participant enrollment; pre-clinical; preclinical study; prophylactic; response; steroid hormone; steroid hormone metabolism; stool sample; treatment response; treatment strategy; tumor progression

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.

项目摘要/摘要 本申请是为了回应被确认为非CA-CA的特殊利益通知(NOSI)而提交的 21比100。 接受乳房切除术的阿片类药物幼稚患者中，每五个人中就有一个在手术一年后持续使用阿片类药物， 强调了乳腺癌女性使用阿片类药物的负担。临床前研究表明，阿片类药物 通过细菌易位和炎性细胞因子的释放对肠道微生物群产生不利影响， 这可能会影响诸如胃肠道紊乱甚至某些疾病的进展等继发性反应 癌症。肠道微生物群也是类固醇激素代谢的场所。具体地说，末端肠道的细菌 微生物组“激活”排泄到胆汁中的结合雌激素，使其重新进入循环。 负责释放这些生物活性雌激素的微生物组成分被称为“雌激素组”。 雌激素代谢产物浓度的增加似乎与肠道微生物多样性密切相关，并且 雌激素代谢产物与血清雌二醇和雌酮的低比率与乳腺癌风险的增加有关 癌症。因此，雌酚胺可能会影响全身性激素和肿瘤的浓度。 结果。本研究旨在描述围手术期阿片类药物对雌酚胺及其受体的影响。 通过比较围手术期肠道的变化，研究乳腺癌患者不同队列中的代谢产物 接受乳腺癌手术的两组患者之间的微生物群：接受标准治疗的患者 基于阿片类药物的疼痛管理和那些接受有效的、不使用阿片类药物的多模式止痛方案的患者。 手术前和术后一周将采集大便和血液样本，以确定围手术期是否 阿片类药物的使用与肠道微生物群的不利变化有关。特定微生物菌株 与阿片类药物诱导的雌酚胺改变相关的将根据抗生素的接受情况(无、低、高)进行分层 以说明围手术期抗生素的潜在影响。除了为其他人提供额外的动力之外 外科医生采用类似的阿片类药物节制围手术期方案，表征阿片类药物对肠道的影响 雌激素敏感型乳腺癌女性患者的雌酚洛姆提供了一种新的创新方法来告知 未来干预目标的发展。