Renal Health Improvement in Diabetes through Microbiome Modulation of the Gut-Kidney Axis with Biotics: A Systematic and Narrative Review of Randomized Controlled Trials.

Diabetes mellitus is the most common endocrine disorder worldwide, with over 20% of patients ultimately developing diabetic kidney disease (DKD), a complex nephropathic complication that is a leading cause of end-stage renal disease. Various clinical trials have utilized probiotics, prebiotics, and synbiotics to attempt to positively modulate the gut microbiome via the gut-kidney axis, but consensus is limited. We conducted a multi-database systematic review to investigate the effect of probiotics, prebiotics, and synbiotics on various biomarkers of renal health in diabetes, based on studies published through 10 April 2022. Adhering to the Cochrane Collaboration and Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, relevant articles were systematically screened and extracted by independent reviewers; subsequently, results were systematically compiled, analyzed, and expanded through a narrative discussion. A total of 16 publications encompassing 903 diabetic individuals met the inclusion criteria. Our findings show that some studies report statistically significant changes in common renal markers, such as serum creatinine, estimated glomerular filtration rate, blood urea nitrogen/urea, microalbuminuria, and uric acid, but not on serum albumin, sodium, potassium, phosphorous, or total urine protein. Interestingly, these nutraceuticals seem to increase serum uric acid concentrations, an inflammatory marker usually associated with decreased renal health. We found that probiotics from the Lactobacillus and Bifidobacterium families were the most investigated, followed by Streptococcus thermophilus. Prebiotics including inulin, galacto-oligosaccharide, and resistant dextrin were also examined. The single-species probiotic soymilk formulation of Lactobacillus plantarum A7 possessed effects on multiple renal biomarkers in DKD patients without adverse events. We further investigated the optimum nutraceutical formulation, discussed findings from prior studies, described the gut-kidney axis in diabetes and DKD, and finally commented on some possible mechanisms of action of these nutraceuticals on renal health in diabetics. Although probiotics, prebiotics, and synbiotics have shown some potential in ameliorating renal health degradation in diabetes via gut-kidney axis crosstalk, larger and more convincing trials with focused objectives and next-generation nutraceutical formulations are required to investigate their possible role as adjunct therapy in such patients.