The gut-kidney axis and inflammation in type 2 diabetes patients

This thesis investigates the gut–kidney axis in chronic kidney disease (CKD) and diabetic kidney disease (DKD), focusing on gut microbiota, inflammation, metabolites, and glucagon-like peptide-1 (GLP-1).
The review of microbiota in DKD shows that CKD and DKD are associated with reduced microbial diversity, fewer beneficial short-chain fatty acid-producing bacteria, and increased production of harmful uremic toxins. Preclinical studies suggest that dietary fibre, probiotics, prebiotics, synbiotics, or faecal microbiota transplantation may reduce inflammation and kidney damage, but clinical trials are still needed.
Using data from the multi-ethnic HELIUS cohort, the thesis also demonstrates ethnic differences in inflammatory biomarkers and their associations with CKD. D-dimer was associated with CKD in South-Asian Surinamese participants, while fibrinogen and D-dimer were associated with CKD in Dutch participants, highlighting the importance of ethnicity in CKD research and treatment.
Untargeted metabolomic analyses identified several metabolites associated with CKD and DKD. Urinary metabolites, mainly lipids, showed stronger associations than plasma metabolites, which were predominantly amino acids. No clear microbial metabolites predicted kidney disease, and ethnicity did not modify the associations.
Finally, the thesis examines GLP-1 receptor agonists, which may protect the kidneys through improved glucose control, blood pressure, weight loss, reduced inflammation, and direct renal effects. However, our interventional study found that exenatide did not restore impaired sodium excretion after oral sodium intake in type 2 diabetes, suggesting that other gut-derived hormones or mechanisms are involved.