The relationship between probiotics and prebiotics, kidney dysfunction and mortality - Results from a longitudinal cohort study and Mendelian randomization.

Introduction: The benefits of probiotics/prebiotics consumption on chronic kidney disease (CKD) and mortality remains controversial.

Objectives: This study investigates the association of probiotics/prebiotics consumption with chronic kidney disease (CKD) and mortality.

Methods: Clinical data were retrieved from the National Health and Nutrition Examination Survey (NHANES) 2005-2016 database. Weighted multivariable logistic and liner regression models, cox proportional hazards models and stratified analysis were used to analyse the relationships between consumption of probiotics/prebiotics, renal parameters, CKD and mortality. We also conducted a two-sample Mendelian randomization (MR) analysis of single nucleotide polymorphisms (SNPs) related to different genera of gut microbiota to assess their causal relationships with CKD and mortality.

Results: 15,291 subjects were analysed (897 with consumption of probiotics/prebiotics and 14,394 without). The use of probiotics/prebiotics showed an inverse correlation with urinary albumin-to-creatinine ratio (UACR) (P < 0.05). Probiotics/prebiotics use was associated with lower risk of CKD in subjects with hypertension, hyperlipidaemia and diabetes mellitus. The consumption of probiotics/prebiotics was associated with a significantly lower risk of all-cause mortality in different regression models (P < 0.001, for all), but the lower risk of cardiovascular mortality did not reach statistical significance (P > 0.05, for all)]. MR analysis showed negative associations between the genetically predicted genus Flavonifractor and risk of CKD and diabetic kidney disease (DKD).

Conclusion: After multivariable regression, and cox proportional hazards analysis, we found that the use of probiotics/prebiotics was associated with improved kidney and mortality outcomes in the general population from NHANES database. The two-sample MR analysis provided further genetic evidence that a distinct genus of gut microbiota was associated with reduced risk of CKD, DKD and mortality.