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P-Cresol Sulfate

P-Cresol Sulfate

Linear Formula

C7H8O4S

Synonyms

p-cresyl sulfate

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What is p-Cresol Sulfate?

P-Cresol sulfate is commonly known as a uremic toxin and is derived from the secondary metabolism of p-cresol1. Uremic toxins can be divided into three categories: 1) water-soluble, non-protein binding, low molecular weight compounds, 2) larger molecular weight compounds, and 3) protein binding, low molecular weight compounds. P-cresol sulfate belongs to the third group of uremic toxins, and due to strong protein binding, it is difficult to remove through dialysis2.

Notably, p-Cresol sulfate is an important biomarker for chronic kidney disease and can accumulate in various organs. Uremic toxins like p-Cresol sulfate can trigger inflammatory responses and induce oxidative stress, thereby exacerbating renal damage.

P-Cresol sulfate is also a tyrosine metabolite produced by certain members of the gut microbiome3. In chronic kidney disease, increased production of P-Cresol sulfate in the gut, along with decreased clearance from the kidneys, results in toxicity that can affect multiple organs in the body.

What is p-Cresol Sulfate?
(Figure from Prokopienko et al., 2017)

P-Cresol Sulfate and cardiovascular health

Considering the close relationship between chronic kidney disease, metabolic health, and adverse cardiovascular outcomes, it is not surprising that p-Cresol sulfate could play a significant role in modulating overall metabolic health. Indeed, researchers have demonstrated that individuals with high levels of serum p-Cresol sulfate are at an increased risk for cardiovascular disease4. However, results can vary; one report found that serum levels of P-cresol sulfate were elevated in obese men while urine levels were decreased5.

Other studies have demonstrated no association between p-cresol sulfate itself and cardiovascular outcomes; however, there is an increased risk of cardiac death in individuals with low serum albumin (another indicator of kidney health) and high levels of p-cresol sulfate6.

P-Cresol Sulfate and gastrointestinal health

The production of p-Cresol sulfate gut microbes combined with decreased elimination during chronic kidney disease can cause severe organ damage. Several recent reports have begun to uncover the relationship between gastrointestinal health, chronic kidney disease, and p-Cresol sulfate. In one study using cats with chronic kidney disease, researchers found decreased fecal bacterial diversity associated with increased levels of uremic toxins such as p-Cresol sulfate7.

Others have identified a potential mechanism where chronic kidney disease triggers increased inflammation that breaks down epithelial tight junctions. Subsequently, gut-derived p-Cresol sulfate then diffuses through the “leaky gut” and induces widespread systemic inflammation8.

P-Cresol Sulfate and neuroscience

Type 1 diabetes is commonly known as a disease affecting peripheral physiology. However, recent data have identified a phenomenon known as gut-brain dysbiosis, where changes in gastrointestinal and metabolic health can directly affect the central nervous system.

One aspect of these changes is brain insulin resistance, where the central nervous system fails to effectively regulate insulin signaling. Interestingly, uremic toxins like p-Cresol sulfate can also have an effect on the brain. In one report examining lean vs. obese mice, researchers found increased levels of p-Cresol sulfate in the cerebrospinal fluid and brain tissue of obese mice. Furthermore, p-Cresol sulfate alters central insulin receptor function by increasing insulin receptor activation and downstream kinases9.

P-Cresol Sulfate and drug development

As a uremic toxin, p-Cresol sulfate levels have been useful in evaluating drug dosage during pharmaceutical development. One report investigated the relationship between urinary metabolite profiles and a widely used analgesic, acetaminophen. The findings revealed that individuals with high urinary levels of p-Cresol sulfate exhibited reduced efficiency in the sulfonation process of acetaminophen metabolism. In other words, p-Cresol sulfate competes with the body’s ability to metabolize acetaminophen efficiently, leading to changes in dose requirements for individuals with chronic kidney disease10.

 

References

  1. National Library of Medicine, National Center for Biotechnology Information (2023). PubChem Compound Summary for p-Cresol sulfate (CID 4615423).
  2. Liu WC, Tomino Y, and Lu KC. Impacts of Indoxyl Sulfate and p-Cresol Sulfate on Chronic Kidney Disease and Mitigating Effects of AST-120. Toxins (Basel) 2018;10(9):367.
  3. Pascal Andreu V, Augustijn HE, Chen L et al. gutSMASH predicts specialized primary metabolic pathways from the human gut microbiota. Nat Biotechnol 2023.
  4. Meijers BK, Bammens B, De Moor B et al. Free p-cresol is associated with cardiovascular disease in hemodialysis patients. Kidney Int 2008;73(10):1174–1180.
  5. Yu HT, Fu XY, Xu B et al. Untargeted metabolomics approach (UPLC-Q-TOF-MS) explores the biomarkers of serum and urine in overweight/obese young men. Asia Pac J Clin Nutr 2018;27(5):1067–1076.
  6. Shafi T, Sirich TL, Meyer TW et al. Results of the HEMO Study suggest that p-cresol sulfate and indoxyl sulfate are not associated with cardiovascular outcomes. Kidney Int 2017;92(6):1484–1492.
  7. Summers SC, Quimby JM, Isaiah A et al. The fecal microbiome and serum concentrations of indoxyl sulfate and p-cresol sulfate in cats with chronic kidney disease. J Vet Intern Med 2019;33(2):662–669.
  8. Lau WL, Kalantar-Zadeh K, and Vaziri ND. The Gut as a Source of Inflammation in Chronic Kidney Disease. Nephron 2015;130(2):92–98.
  9. Leboucher A, Rath M, and Kleinridders A. Increased uremic toxins in cerebrospinal fluid of obese mice cause insulin resistance. Diabetologie und Stoffwechsel 2018;13(S 01):S21.
  10. Clayton TA, Baker D, Lindon JC et al. Pharmacometabonomic identification of a significant host-microbiome metabolic interaction affecting human drug metabolism. Proc Natl Acad Sci U S A 2009;106(34):14728–14733.
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References

1. Zgoda-Pols, J.R., et al., Metabolomics analysis reveals elevation of 3-indoxyl sulfate in plasma and brain during chemically-induced acute kidney injury in mice: investigation of nicotinic acid receptor agonists. Toxicol Appl Pharmacol, 2011. 255(1): p. 48-56.

2. Bryant, J.A., et al., The impact of an oral purified microbiome therapeutic on the gastrointestinal microbiome. Nat Med, 2026. 32(1): p. 186-196

3. McGovern, B .H., et al., SER-109, an Investigational Microbiome Drugto Reduce Recurrence After Clostridioides difficile Infection: Lessons Learned From a Phase 2 Trial. Clin Infect Dis, 2021. 72(12): p. 2132-2140.

4. Feuerstadt, P., et al., SER-109, an Oral Microbiome Therapy for Recurrent Clostridioides difficile Infection. N Engl J Med, 2022. 386(3): p. 220-229.

5. Hu, Z., et al., Targeted metabolomics reveals novel diagnostic biomarkers for colorectal cancer. Mol Oncol, 2025. 19(6): p. 1737-1750.

6. Butler, F.M., et al., Vegetarian Dietary Patterns and Diet-Related Metabolites Are Associated With Kidney Function in the Adventist Health Study-2 Cohort. J Ren Nutr, 2025.

7. Stanford, J., et al., Metabolomic Profiling and Diet Quality Scoring in a Randomized Crossover Trial of Healthy and Typical Dietary Patterns. Mol Nutr Food Res, 2025 . 69(23): p. e70271.

8. O’Connor, L.E., et al., Metabolomic Profiling of an Ultraprocessed Dietary Pattern in a Domiciled Randomized Controlled Crossover Feeding Trial. J Nutr, 2023. 153(8): p. 2181-2192.

9. Fritsch, D.A., et al., Microbiome function underpins the efficacy of a fiber-supplemented dietary intervention in dogs with chronic large bowel diarrhea. BMC Vet Res, 2022. 18(1): p. 245.

10. Leal, L.N., et al., Preweaning nutrient supply improves lactation productivity and reduces the risk of culling in Holstein cows. J Dairy Sci, 2025. 108(6): p. 5875-5888.

11. Ahsin, M., et al., Soil and pasture health underlie improved beef nutrient density determined by untargeted metabolomics in Southern US grass finished beef systems. NPJ Sci Food, 2025. 9(1): p. 151.

12. Yin, W., et al., Plasma lipid profiling across species for the identification of optimal animal models of human dyslipidemia. J Lipid Res, 2012. 53(1): p. 51-65.

13. Porter, F .D., et al., Cholesterol oxidation products are sensitive and specific blood-based biomarkers for Niemann-Pick C1 disease. Sci Transl Med, 2010. 2(56): p. 56ra81.

14. Needham, B .D., et al., Plasma and Fecal Metabolite Profiles in Autism Spectrum Disorder. Biol Psychiatry, 2021. 89(5): p. 451-462

15. Li, C., et al., Estradiol and mTORC2 cooperate to enhance prostaglandin biosynthesis and tumorigenesis in TSC2-deficient LAM cells. J Exp Med, 2014. 211(1): p. 15-28.

16. Green, P.G., et al., Metabolic flexibility and reverse remodelling of the failing human heart. Eur Heart J, 2025. 46(25): p. 2422-2433.

17. Maekawa, H., et al., SGLT2 inhibition protects kidney function by SAM-dependent epigenetic repression of inflammatory genes under metabolic stress. J Clin Invest, 2025. 135(19).

18. Wu, D., et al., Integrated screens reveal that guanine nucleotide depletion, which is irreversible via targeting IMPDH2, inhibits pancreatic cancer and potentiates KRAS inhibition. Gut, 2026.

19. Schwerdtfeger, L.A., et al., Gut microbiota and metabolites are linked to disease progression in multiple sclerosis. Cell Rep Med, 2025. 6(4): p. 102055.

20. Wu, H., et al., Microbiome-metabolome dynamics associated with impaired glucose control and responses to lifestyle changes. Nat Med, 2025. 31(7): p. 2222-2231.

21. Jacobs, J.P., et al., Cognitive behavioral therapy for irritable bowel syndrome induces bidirectional alterations in the brain-gut-microbiome axis associated with gastrointestinal symptom improvement. Microbiome, 2021. 9(1): p. 236.

22. Pietzner, M., et al., Plasma metabolites to profile pathways in noncommunicable disease multimorbidity. Nat Med, 2021. 27(3): p. 471-479.

23. Faquih, T.O., et al., Robust Metabolomic Age Prediction Based on a Wide Selection of Metabolites. J Gerontol A Biol Sci Med Sci, 2025. 80(3).

24. Scherer, N., et al., Coupling metabolomics and exome sequencing reveals graded effects of rare damaging heterozygous variants on gene function and human traits. Nat Genet, 2025. 57(1): p. 193-205.

25. Holmes, Z.C., et al., Untargeted metabolomic analysis of human milk from healthy mothers reveals drivers of metabolite variability. Sci Rep, 2024. 14(1): p. 20827.

26. Titz, B., et al., Implications of Ocular Confounding Factors for Aqueous Humor Proteomic and Metabolomic Analyses in Retinal Diseases. Transl Vis Sci Technol, 2024. 13(6): p. 17.

27. Bloom, S.M., et al., Cysteine dependence of Lactobacillus iners is a potential therapeutic target for vaginal microbiota modulation. Nat Microbiol, 2022. 7(3): p. 434-450.

28. Leimer, E.M., et al., Lipid profile of human synovial fluid following intra-articular ankle fracture. J Orthop Res, 2017. 35(3): p. 657-666.