Evidence of a causal and modifiable relationship between kidney function and circulating trimethylamine N-oxide.
Nat Commun
; 14(1): 5843, 2023 09 20.
Article
in En
| MEDLINE
| ID: mdl-37730687
ABSTRACT
The host-microbiota co-metabolite trimethylamine N-oxide (TMAO) is linked to increased cardiovascular risk but how its circulating levels are regulated remains unclear. We applied "explainable" machine learning, univariate, multivariate and mediation analyses of fasting plasma TMAO concentration and a multitude of phenotypes in 1,741 adult Europeans of the MetaCardis study. Here we show that next to age, kidney function is the primary variable predicting circulating TMAO, with microbiota composition and diet playing minor, albeit significant, roles. Mediation analysis suggests a causal relationship between TMAO and kidney function that we corroborate in preclinical models where TMAO exposure increases kidney scarring. Consistent with our findings, patients receiving glucose-lowering drugs with reno-protective properties have significantly lower circulating TMAO when compared to propensity-score matched control individuals. Our analyses uncover a bidirectional relationship between kidney function and TMAO that can potentially be modified by reno-protective anti-diabetic drugs and suggest a clinically actionable intervention for decreasing TMAO-associated excess cardiovascular risk.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Endocrinology
/
Methylamines
Type of study:
Prognostic_studies
Limits:
Adult
/
Humans
Language:
En
Journal:
Nat Commun
Year:
2023
Document type:
Article