Association of blood and microbial biomarkers in assessment of progressive CKD in stage IV and dialysis patients using a genomics and metabolomics approach
| Author(s) | Vyas, Usha N. | |
| Date Accessioned | 2024-09-23T14:39:23Z | |
| Date Available | 2024-09-23T14:39:23Z | |
| Publication Date | 2024 | |
| SWORD Update | 2024-08-31T19:01:48Z | |
| Abstract | Background: Chronic diseases are irreversible, and patients undergo lifetime treatments and medications. In Chronic Kidney Disease (CKD) serum creatinine as the clinically used biomarker has several drawbacks. Disease can progress leading to side effects, altered microbial gut ecology, and altered diet. All of these collectively disturb the natural ecosystem in the colon which houses commensal bacteria, and the symbionts and pathobionts. An imbalanced gut ecosystem which mainly consists of gut bacteria produce metabolites which are toxic to human health. In CKD imbalanced gut microbes and gut related toxins are produced which is termed as the gut -kidney health. These toxins are protein bound and not completely cleared even by hemodialysis. Thus, multiple biomarkers which increase with disease progression are needed for diagnosis which can be used as target for therapeutic application The aim of this research was twofold 1) To identify specific serum biomarkers which increase with CKD progression.2) To identify fecal microbial signatures specific to disease progression. Methods: Serum and fecal samples for healthy, CKD IV patients and hemodialysis patients were obtained from the sponsor, biobank, and University of Delaware IRB approved protocol. UPLC/MS and ELISA for serum samples were done at the sponsor’s lab. Fecal 16S rRNA sequencing and bioinformatics were done at the University of Delaware. Summary: Kidney injury marker (NGAL), protein bound uremic toxins p-cresyl sulfate (PCS) and indoxyl sulfate (IS), cardiovascular uremic toxin trimethylamine-N-oxide (TMAO), and inflammatory biomarker IL-6 were found to be the best for studying disease progression. Fecal microbiome analysis using QIIME2 showed no significance in the alpha diversity. PERMANOVA, ANOSIM, and ANCOM-BC showed significant differences in the healthy and diseased groups. There was significant depletion in the levels of beneficial bacteria Fecalibacterium, B. longum, B. adolescentis, Lactobacillus, E. rectale, Coprococcus comes, and Lachnospira with CKD progression and enhanced levels of pathogenic bacteria like Proteobacteria, Desulfovibrio, Enterococus, Ruminococcus, P. faecium, C. asparagiforme and E. faecalis. In clinical study using a probiotic intervention the levels of these serum biomarkers and fecal microbiome signatures can be measured to see the therapeutic efficacy and disease attenuation. ☐ This thesis is an industry sponsored Ph.D. Kibow Biotech, Inc is the sponsor of this research. | |
| Advisor | Biddle, Amy S. | |
| Degree | Ph.D. | |
| Department | University of Delaware, Department of Animal and Food Sciences | |
| DOI | https://doi.org/10.58088/5nee-jz06 | |
| Unique Identifier | 1461768076 | |
| URL | https://udspace.udel.edu/handle/19716/35022 | |
| Language | en | |
| Publisher | University of Delaware | |
| URI | https://www.proquest.com/pqdtlocal1006271/dissertations-theses/association-blood-microbial-biomarkers-assessment/docview/3099344922/sem-2?accountid=10457 | |
| Keywords | Hemodialysis | |
| Keywords | Microbiomes | |
| Keywords | PacBio | |
| Keywords | Kidney injury markers | |
| Keywords | Uremic toxins | |
| Title | Association of blood and microbial biomarkers in assessment of progressive CKD in stage IV and dialysis patients using a genomics and metabolomics approach | |
| Type | Thesis |