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.

项目总结/文摘