Heritability and clinical determinants of serum indoxyl sulfate and p-cresyl sulfate, candidate biomarkers of the human microbiome enterotype.
BACKGROUND
Indoxyl sulfate and p-cresyl sulfate are unique microbial co-metabolites. Both co-metabolites have been involved in the pathogenesis of accelerated cardiovascular disease and renal disease progression. Available evidence suggests that indoxyl sulfate and p-cresyl sulfate may be considered candidate biomarkers of the human enterotype and may help to explain the link between diet and cardiovascular disease burden.


OBJECTIVE
Information on clinical determinants and heritability of indoxyl sulfate and p-cresyl sulfate serum is non-existing. To clarify this issue, the authors determined serum levels of indoxyl sulfate and p-cresyl sulfate in 773 individuals, recruited in the frame of the Flemish Study on Environment, Genes and Health Outcomes (FLEMENGHO study).


RESULTS
Serum levels of indoxyl sulfate and p-cresyl sulfate amounted to 3.1 (2.4-4.3) and 13.0 (7.4-21.5) μM, respectively. Regression analysis identified renal function, age and sex as independent determinants of both co-metabolites. Both serum indoxyl sulfate (h2 = 0.17) and p-cresyl sulfate (h2 = 0.18) concentrations showed moderate but significant heritability after adjustment for covariables, with significant genetic and environmental correlations for both co-metabolites.


CONCLUSIONS
Family studies cannot provide conclusive evidence for a genetic contribution, as confounding by shared environmental effects can never be excluded.


CONCLUSIONS
The heritability of indoxyl sulfate and p-cresyl sulfate is moderate. Besides genetic host factors and environmental factors, also renal function, sex and age influence the serum levels of these co-metabolites.
Department of Medicine, Division of Nephrology, Dialysis and Renal Transplantation, University Hospital Leuven, Leuven, Belgium.
Liesbeth
L
Viaene
Studies Coordinating Centre, Division of Hypertension and Cardiovascular Rehabilitation, Department of Cardiovascular Diseases, University of Leuven, Leuven, Belgium.
Lutgarde
L
Thijs
Studies Coordinating Centre, Division of Hypertension and Cardiovascular Rehabilitation, Department of Cardiovascular Diseases, University of Leuven, Leuven, Belgium.
Yu
Y
Jin
Studies Coordinating Centre, Division of Hypertension and Cardiovascular Rehabilitation, Department of Cardiovascular Diseases, University of Leuven, Leuven, Belgium.
Yanping
Y
Liu
Studies Coordinating Centre, Division of Hypertension and Cardiovascular Rehabilitation, Department of Cardiovascular Diseases, University of Leuven, Leuven, Belgium.
Yumei
Y
Gu
Department of Medicine, Division of Nephrology, Dialysis and Renal Transplantation, University Hospital Leuven, Leuven, Belgium.
Björn
B
Meijers
Department of Medicine, Division of Nephrology, Dialysis and Renal Transplantation, University Hospital Leuven, Leuven, Belgium.
Kathleen
K
Claes
Studies Coordinating Centre, Division of Hypertension and Cardiovascular Rehabilitation, Department of Cardiovascular Diseases, University of Leuven, Leuven, Belgium; Department of Epidemiology, Maastricht University, Maastricht, Netherlands.
Jan
J
Staessen
Department of Medicine, Division of Nephrology, Dialysis and Renal Transplantation, University Hospital Leuven, Leuven, Belgium.
Pieter
P
Evenepoel
D000328:Adult; D015415:Biomarkers / Q000097:blood; D002318:Cardiovascular Diseases / Q000097:blood / Q000235:genetics; D003408:Cresols / Q000097:blood*; D003430:Cross-Sectional Studies; D004032:Diet; D005260:Female; D006801:Humans; D007200:Indican / Q000097:blood*; D008297:Male; D064307:Microbiota; D008875:Middle Aged; D013463:Sulfuric Acid Esters / Q000097:blood*; D055815:Young Adult
D015415:Biomarkers; D003408:Cresols; D013463:Sulfuric Acid Esters; C408690:4-cresol sulfate; D007200:Indican