Serum concentrations of indoxyl sulfate and p-cresyl sulfate are emerging as potential biomarkers reflecting the metabolic activity of the human gut microbiome. These two microbial co-metabolites originate from the colonic fermentation of dietary proteins—indole from tryptophan and p-cresol from tyrosine—and are subsequently sulfated in the liver. They are primarily eliminated via renal tubular secretion, making their serum levels sensitive to both gut microbial activity and kidney function. Elevated levels have been linked to chronic kidney disease progression, cardiovascular morbidity, and increased mortality, suggesting a role in mediating diet–health relationships.
This study aimed to evaluate the heritability and clinical determinants of serum indoxyl sulfate and p-cresyl sulfate in a large, randomly selected cohort of white Europeans. Data were derived from the Flemish Study on Environment, Genes and Health Outcomes (FLEMENGHO), including 773 individuals with available measurements for indoxyl sulfate and 751 for p-cresyl sulfate. Participants underwent standardized assessments of blood pressure, anthropometrics, medication use, medical history, and laboratory tests, including serum creatinine and estimated glomerular filtration rate using the Cockcroft-Gault formula.9-Bromononanoic acid medchemexpress
Mean serum concentrations were 3.1 (2.4–4.3) μmol/L for indoxyl sulfate and 13.0 (7.4–21.5) μmol/L for p-cresyl sulfate. After logarithmic transformation to normalize distributions, regression analyses revealed that age, sex, and renal function were independent predictors of both metabolites. Notably, serum levels increased significantly with age, particularly after 50 years, and men exhibited higher concentrations than women. Lower renal clearance was strongly associated with elevated toxin levels, consistent with their status as uremic retention solutes.Ethyl pent-4-ynoate Protocol
Heritability analysis using the Statistical Analysis for Genetic Epidemiology (S.PMID:34137911 A.G.E.) software showed moderate but significant heritability: h² = 0.16 for indoxyl sulfate and h² = 0.24 for p-cresyl sulfate after full adjustment for covariates. The genetic correlation between the two metabolites was positive, indicating shared genetic influences. Environmental factors also contributed significantly, especially within families living together, although the influence of shared environment could not be fully disentangled from genetics due to confounding.
Smoking and alcohol consumption were associated with lower levels of both metabolites, though these associations attenuated in multivariable models. Higher triglycerides and systolic blood pressure correlated with increased indoxyl sulfate, while only renal function remained independently associated with p-cresyl sulfate after adjusting for age. Dietary intake data were not available in this cohort, limiting direct assessment of nutritional impacts, though prior studies suggest high-protein and low-fiber diets elevate these toxins.
In conclusion, indoxyl sulfate and p-cresyl sulfate exhibit moderate heritability influenced by age, sex, renal function, and lifestyle factors. Their serum levels reflect a complex interplay between host genetics, gut microbiota dynamics, and environmental exposures. As candidate biomarkers of the human enterotype—particularly the Bacteroides-dominant type—they may help bridge the gap between dietary patterns and cardiovascular risk. Future research should explore whether these metabolites can refine cardiovascular risk prediction beyond traditional markers and whether modulating the gut microbiome through diet or prebiotics can reduce their levels and improve health outcomes.MedChemExpress (MCE) offers a wide range of high-quality research chemicals and biochemicals (novel life-science reagents, reference compounds and natural compounds) for scientific use. We have professionally experienced and friendly staff to meet your needs. We are a competent and trustworthy partner for your research and scientific projects.Related websites: https://www.medchemexpress.com