Abstract
BackgroundIndoxyl 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 and DesignInformation 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).ResultsSerum 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.LimitationsFamily studies cannot provide conclusive evidence for a genetic contribution, as confounding by shared environmental effects can never be excluded.ConclusionsThe 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.
Highlights
The human intestinal tract is colonized by hundreds of trillions of microbes, which collectively possess hundreds of times as many genes as coded for by the human genome
The median serum concentration amounted to 3.19 mM for indoxyl sulfate and to 13.03 mM for pcresyl sulfate
Distribution range for serum concentration of either toxin was skewed with respectively 26% and 10% (p-cresyl sulfate) of the participants being at the limit of quantification (LOQ) (Figure 1)
Summary
The human intestinal tract is colonized by hundreds of trillions of microbes, which collectively possess hundreds of times as many genes as coded for by the human genome. Metabolites derived from the microbial community are referred to as co-metabolites. This metabolic phenotype provides a readout of the metabolic state of an individual and is the product of genetic and environmental (diet, liefestyle, gut microbial activity) contributions under a particular set of conditions [5]. 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
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
