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.