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The Gut Microbiome and Serum Metabolites as a Biological Mechanism Underlying Pain in Kidney Transplantation (Biome-KT)

肠道微生物组和血清代谢物作为肾移植疼痛的生物机制 (Biome-KT)

基本信息

批准号：
10633444
负责人：
Mark Lockwood
金额：
$ 61.66万
依托单位：
UNIVERSITY OF ILLINOIS AT CHICAGO
依托单位国家：
美国
项目类别：
财政年份：
2023
资助国家：
美国
起止时间：
2023-05-15 至 2028-02-29
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10633444
关键词：
Address Adult Affect Age Anxiety Bacteria Biological Biological Markers Brain Catabolism Chemicals Chronic Kidney Failure Clinical Cognitive Communities Consumption Data Diet Dietary Practices Disease Emotional End stage renal failure Endocrine Endotoxins Enterococcus Environmental Risk Factor Fatigue Fatty acid glycerol esters Feces Fiber Foundations Gastrointestinal tract structure General Population Genes Goals Growth Hemodialysis Human body Immunologics Immunosuppression Impairment Income Indoles Inflammation Intervention Intestines Investigation Kidney Kidney Diseases Kidney Transplantation Kynurenic Acid Kynurenine Life Link Longitudinal Studies Measures Mediating Mental Depression Metabolic Microbe Modeling Neuropathy Nociception Pain Pain intensity Pain interference Pain management Pathway interactions Patient Self-Report Persons Phenotype Play Probiotics Psychological Stress Quinolinic Acid Race Recreation Renal function Reporting Risk Role Serotonin Serum Signaling Molecule Stress Supplementation Testing Time Toxin Transplant Recipients Transplantation Treatment Protocols Tryptophan Urea Volatile Fatty Acids Withdrawal beta diversity chemical reduction chronic pain comorbidity daily functioning design experience food consumption gut microbiome gut microbiota health related quality of life host-microbe interactions improved indexing indoleacetic acid innovation machine learning algorithm machine learning model microbial microbial community microbial composition microbiome microbiota microorganism mortality multimodality neurotoxic novel pain reduction pain relief pain score painful neuropathy patient oriented patient population perceived stress post-transplant prevent prospective restoration social stress reduction sugar systemic inflammatory response transplant model treatment adherence treatment optimization

项目摘要

7. Abstract Nearly half (47%) of people with end-stage kidney disease (ESKD) whose kidney function is restored after kidney transplantation experience chronic pain compared to 19% of adults in the US general population. Pain is associated with comorbid fatigue, depression and anxiety, and withdrawal from usual physical and social activities; resulting in an inability to participate in and enjoy life. Severe pain can result in nonadherence to immunosuppression and treatment protocols and result in an increased risk of rejection, graft loss, and mortality. The role of symbiotic microbes (microbiota) in the gastrointestinal tract, and their functional genes (microbiome), is well established in diseases involving pain. Diet and stress play a major role in synthesis of signaling molecules critical to immunologic, metabolic, and endocrine pathways regulating chronic pain. Dietary patterns change dramatically after transplantation, as recipients move from a restricted “renal” diet to a regular diet, often resulting in increased consumption of foods high in sugars and fat. Moreover, psychological stress significantly impairs the function of the microbiome, initiating biological pathways involved in pain, leading to a disproportionate pain burden. Because the microbiome, serum metabolites, and pain are dynamic, our novel investigation will employ a prospective repeated measures design to interrogate the dynamic temporal relationships between the microbiome, metabolites associated with pathways regulating pain, transplantation factors (e.g. immunosuppression, kidney function), changing dietary patterns, and perceived stress, on pain scores before and after kidney transplantation. We posit the gut microbiome, and its byproducts, may partially explain the underlying biological mechanisms of pain Interference in kidney disease. We will address three aims: 1) To determine differential dynamic temporal relationships between microbial composition/functional genes and circulating serum metabolites in KTRs with pain vs no pain, 2) To determine the moderation effects of diet and perceived stress on dynamic temporal relationships between microbiome features, serum metabolites, and pain scores among KTRs, and 3) To use machine learning algorithms to identify host-microbial interactions that are causally linked to pain interference among KTRs. Because kidney function is restored, the kidney transplant model is powerful to study the longitudinal relationships between the microbiome, circulating metabolites and chronic pain in people with ESKD to develop patient-centered interventions to treat pain across the spectrum of CKD.

7. 摘要