Research Project
The Gut Microbiome and Serum Metabolites as a Biological Mechanism Underlying Pain in Kidney Transplantation (Biome-KT)
People with end-stage kidney disease may experience moderate to severe pain as a result of the inability of their kidneys to filter toxins that cause inflammation, and for many pain persists after restoration of kidney function following kidney transplantation. We all coexist with trillions of bacteria and other microbes, collectively known as the microbiome, that live in communities on and within the human body and make chemicals that reduce or exacerbate pain through the brain-gut-microbiome-axis. The goal of this study is to better understand how the communities of microbes, and the chemicals they produce that may affect pain, change after kidney transplantation, and how these changes affect pain over time in order to develop patient-centered treatments for pain by manipulating the microbiome through diet, stress reduction, and or supplementation with pre/probiotics
- Principal Investigator
- Lockwood, Mark B.
- Start Date
- 2023-05-15
- End Date
- 2028-02-29
- Funding Source
- National Institute of Diabetes, Digestive & Kidney Disorders
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.