Changes in Oral and Gut Microbiota and Incidence and Severity of Patient-Reported Symptoms in Pre- and Post-Kidney Transplant Patients

摘要 这项新的前瞻性队列研究将探索肾移植(抗生素， 抗病毒药物和免疫抑制剂)的组成和功能基因含量的变化 微生物组，以及在患者接受治疗前后患者报告的症状的发生率和严重程度 活体捐赠者的肾脏移植。我们挑选了活体捐赠者，以减少失踪的机会 样本，因为这些都是预定的手术。39名受试者将提供粪便和痰样本进行注射 移植前、移植后第一周移植前微生物组元基因组测序 于移植后3个月出院。人口统计(年龄、性别、种族/民族、收入、 教育)和疾病特定数据(HT/WT/BMI、肌酐、估计肾小球滤过率、基础 代谢面板、完整血细胞计数)和服药依从性数据(电子服药依从性 监测和他克莫司低谷水平)将被收集。潜在的混杂变量包括：历史 抗生素、配套药物、分娩方式(阴道分娩与剖腹产)和营养的使用 现状(饮食历史问卷三)。疲劳、睡眠障碍等症状的发生率和严重程度 焦虑/抑郁样症状将使用患者报告的结果测量来衡量 系统(PROMIS)57 v2.1。与健康相关的生活质量将使用肾脏疾病质量评估 生命简表(KDQOL-SF v1.3)。这项研究将支持国家护理研究所的使命 研究(NINR)，以促进和改善个人、家庭和 社区。拟议的研究将通过以下方式为NINR任务做出贡献：1)探索 肾移植后潜在症状的发生率和严重程度 个性化治疗，包括益生菌前补充、改变生活方式和饮食 通过症状科学研究解决这些机制的干预措施；2)帮助个人 慢性肾脏疾病/肾移植受者通过以下方式更好地了解和管理这些情况 让个人作为积极参与者参与管理自己的健康，通过意识到可修改 改变微生物组的因素；以及3)促进创新、多学科、护士主导的发展 团队推进肾移植后微生物群与健康的研究。

Abstract This novel prospective cohort study will explore the relationship between kidney transplantation (antibiotics, antivirals, and immunosuppressants), changes in the composition and functional gene content of the microbiome, and the incidence and severity of patient reported symptoms before and after patients receive a kidney transplant from a live donor. We have selected living donor recipients to reduce the chance of missing samples, as these are scheduled surgeries. Thirty-nine subjects will provide stool and sputum samples for shot gun metagenomic sequencing of the microbiome before transplant, during the first week after transplant prior to discharge, and at 3 months after the transplant. Demographic (age, gender, race/ethnicity, income, education) and disease specific data (HT/WT/BMI, creatinine, estimated glomerular filtration rate, basic metabolic panel, complete blood count), and medication adherence data (electronic medication adherence monitoring and tacrolimus trough levels) will be collected. Potential confounding variables will include: historical use of antibiotics, concomitant medications, mode of delivery (vaginal vs. caesarian birth), and nutritional status (Diet History Questionnaire III). Incidence and severity of symptoms of fatigue, sleep dysfunction, and anxiety/depression–like symptoms will be measured using the Patient Reported Outcome Measurement Systems (PROMIS) 57 v2.1. Health related quality of life will be assessed using the Kidney Disease Quality of Life Short Form (KDQOL-SF v1.3). This research will support the mission of the National Institute of Nursing Research (NINR) to promote and improve the health and quality of life of individuals, families, and communities. The proposed study will contribute to the NINR mission by: 1) Exploring the mechanisms underlying incidence and severity of symptoms after kidney transplantation with the goal of developing personalized treatments, including pre-probiotics supplementation, lifestyle modification, and dietary interventions that address these mechanisms through symptom science research; 2) Helping individuals with chronic kidney disease/kidney transplant recipients better understand and manage these conditions by engaging individuals as active participants in managing their own health through awareness of modifiable factors that alter the microbiome; and 3) Promoting the development of innovative, multidisciplinary, nurse-led teams to advance research on microbiome and health after kidney transplantation.