Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2020 Apr 11;12(4):245.
doi: 10.3390/toxins12040245.

Gut-Derived Metabolites and Their Role in Immune Dysfunction in Chronic Kidney Disease

Griet Glorieux  1 , Tessa Gryp  1 , Alessandra Perna  2
Affiliations
Review

Gut-Derived Metabolites and Their Role in Immune Dysfunction in Chronic Kidney Disease

Griet Glorieux et al. Toxins (Basel). .

Abstract

Several of the uremic toxins, which are difficult to remove by dialysis, originate from the gut bacterial metabolism. This opens opportunities for novel targets trying to decrease circulating levels of these toxins and their pathophysiological effects. The current review focuses on immunomodulatory effects of these toxins both at their side of origin and in the circulation. In the gut end products of the bacterial metabolism such as p-cresol, trimethylamine and H2S affect the intestinal barrier structure and function while in the circulation the related uremic toxins stimulate cells of the immune system. Both conditions contribute to the pro-inflammatory status of patients with chronic kidney disease (CKD). Generation and/or absorption of these toxin precursors could be targeted to decrease plasma levels of their respective uremic toxins and to reduce micro-inflammation in CKD.

Keywords: chronic kidney disease; gut; immune; uremic toxins.

PubMed Disclaimer

Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
End products of the intestinal bacterial metabolism (I, IAA, pC, TMA, H2S) are transported as such or after detoxification (sulfatation and glucuronidation) towards the liver via the portal vein where the remaining pC and I are conjugated and TMA is oxygenated. The end products of the bacterial and human metabolism are taken up into the circulation (IxS, IAA, pCS, pCG, TMAO, H2S) where some bind to albumin (IxS, IAA, pCS and to a lesser extend pCG). H2S is also generated by different tissues throughout the body. Finally, these compounds are excreted into the urine. Trp: tryptophan; Tyr: tyrosine; Cys: cysteine; I: indole; IAA: indole-3-acetic acid; pC: p-cresol; TMA: trimethylamine; TMAO: trimethylamine N-oxide; pCS: p-cresyl sulfate; pCG: p-cresyl glucuronide; IxS: indoxyl sulfate.
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

References

    1. Medzhitov R. Origin and physiological roles of inflammation. Nature. 2008;454:428–435. doi: 10.1038/nature07201. - DOI - PubMed
    1. Zewinger S., Schumann T., Fliser D., Speer T. Innate immunity in CKD-associated vascular diseases. Nephrol. Dial. Transplant. 2016;31:1813–1821. doi: 10.1093/ndt/gfv358. - DOI - PubMed
    1. Vaziri N.D., Zhao Y.Y., Pahl M.V. Altered intestinal microbial flora and impaired epithelial barrier structure and function in CKD: The nature, mechanisms, consequences and potential treatment. Nephrol. Dial. Transplant. 2016;31:737–746. doi: 10.1093/ndt/gfv095. - DOI - PubMed
    1. Aronov P.A., Luo F.J., Plummer N.S., Quan Z., Holmes S., Hostetter T.H., Meyer T.W. Colonic contribution to uremic solutes. J. Am. Soc. Nephrol. JASN. 2011;22:1769–1776. doi: 10.1681/ASN.2010121220. - DOI - PMC - PubMed
    1. Mair R.D., Sirich T.L., Plummer N.S., Meyer T.W. Characteristics of Colon-Derived Uremic Solutes. Clin. J. Am. Soc. Nephrol. CJASN. 2018;13:1398–1404. doi: 10.2215/CJN.03150318. - DOI - PMC - PubMed

Publication types

MeSH terms