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.

项目概要/摘要 本申请是为了响应被识别为 NOT-CA- 的特殊利益通知 (NOSI) 而提交的 21-100。 接受乳房切除术的五分之一未使用过阿片类药物的患者在手术一年后仍持续使用阿片类药物， 强调了患有乳腺癌的女性使用阿片类药物的负担。临床前研究表明阿片类药物 通过细菌移位和炎症细胞因子的释放对肠道微生物组产生不利影响， 这可能会影响胃肠道疾病等副作用，甚至某些疾病的进展 癌症。肠道微生物组也是类固醇激素代谢的场所。具体来说，远端肠道的细菌 微生物组“重新激活”排泄到胆汁中的结合雌激素，使其重新进入循环。这 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 雌激素代谢物与血清雌二醇和雌酮的比例较低与乳腺癌风险增加相关 癌症。因此，雌曲醇组可能会影响性类固醇和肿瘤药物的全身浓度。 结果。该提案旨在描述围手术期阿片类药物对雌曲醇组及其影响的特征 通过比较围手术期肠道变化，研究不同乳腺癌女性群体的代谢情况 接受乳腺癌手术的两组患者之间的微生物组：接受标准治疗的患者 基于阿片类药物的疼痛管理和接受经过验证的、不含阿片类药物的多模式镇痛方案的患者。 将在手术前和手术后一周收集粪便和血液样本，以确定围手术期是否 阿片类药物的施用与肠道微生物组的不良变化有关。特定微生物菌株 与阿片类药物引起的雌激素变化相关的变化将根据抗生素接受情况进行分层（无、低、高） 考虑围手术期抗生素的潜在影响。除了给其他方面带来额外的推动力 外科医生采用类似的阿片类药物节约围手术期方案，描述阿片类药物对肠道的影响 雌激素敏感型乳腺癌女性的雌激素博洛组提供了一种新颖且创新的方法来告知 制定未来干预目标。