Microbiome in Chronic Kidney Disease (CKD): An Omics Perspective

Abstract

Chronic kidney disease (CKD) is predominant in 10% of the world’s adult population, and is increasingly considered a silent epidemic. Gut microbiota plays an essential role in maintaining host energy homeostasis and gut epithelial integrity. Alterations in gut microbiota composition, functions and, specifically, production of metabolites causing uremic toxicity are often associated with CKD onset and progression. Here, we present the latest omics (transcriptomics, proteomics and metabolomics) studies that explore the connection between CKD and gut microbiome. A review of the available literature using PubMed was performed using the keywords “microb*”, “kidney”, “proteom”, “metabolom” and “transcript” for the last 10 years, yielding a total of 155 publications. Following selection of the relevant studies (focusing on microbiome in CKD), a predominance of metabolomics (n = 12) over transcriptomics (n = 1) and proteomics (n = 6) analyses was observed. A consensus arises supporting the idea that the uremic toxins produced in the gut cause oxidative stress, inflammation and fibrosis in the kidney leading to CKD. Collectively, findings include an observed enrichment of Eggerthella lenta, Enterobacteriaceae and Clostridium spp., and a depletion in Bacteroides eggerthii, Roseburia faecis and Prevotella spp. occurring in CKD models. Bacterial species involved in butyrate production, indole synthesis and mucin degradation were also related to CKD. Consequently, strong links between CKD and gut microbial dysbiosis suggest potential therapeutic strategies to prevent CKD progression and portray the gut as a promising therapeutic target.

Generally-healthy individuals with aberrant bowel movement frequencies show enrichment for microbially-derived blood metabolites associated with reduced kidney function

“…Many of the genera and metabolites that were associated with constipation in this study have been associated with constipation in other disease cohorts and with a variety of risk factors for chronic diseases, like CKD, cardiovascular disease, and metabolic syndrome [8,23,49,50]. Alistipes and Ruminococcus were enriched in end-stage renal disease (ESRD) patients [51], as well as in our generally-healthy cohort at lower BMF levels ( Fig. 4 ).…”

Association between gut microbiota and onset of type 2 diabetes mellitus: a two-sample Mendelian randomization study

“…The role of faecis , a type of bacteria from human feces, in the pathogenesis of T2DM is still unknown. Among patients with chronic diseases, such as chronic kidney disease ( Lohia et al., 2022 ), Chrohn’s disease ( Bao et al., 2022 ), and gastrointestinal cancers ( Li et al., 2021 ), the abundance of Roseburia faecis is obeserved to be significantly reduced. The more consistent speculation about the mechanism by which Roseburia faecis play a beneficial role in these diseases is that it can ferment dietary fiber into butyrate, which was considered to be a protector of the gut ( Wang et al., 2012 ).…”

Prevalence and Severity of Lower Gastrointestinal Symptoms amongst Non-Dialysis Chronic Kidney Disease Patients: A Systematic Review and Meta-Analysis

“…In addition, because of the paucity of data, there is a need to assess the prevalence, risk factors, and implications of functional disorders in CKD; the optimal way is to use the Rome IV Diagnostic Questionnaire for Functional Gastrointestinal Disorders in Adults. The use of specialized questionnaires will improve understanding of patients’ GI symptoms and, when combined with multi-omics data, may reveal the role of GI symptoms in the gut–kidney axis in CKD [ 82 ].…”