Diet posttranslationally modifies the mouse gut microbial proteome to modulate renal function

Science. 2020 Sep 18;369(6510):1518-1524. doi: 10.1126/science.abb3763.


Associations between chronic kidney disease (CKD) and the gut microbiota have been postulated, yet questions remain about the underlying mechanisms. In humans, dietary protein increases gut bacterial production of hydrogen sulfide (H2S), indole, and indoxyl sulfate. The latter are uremic toxins, and H2S has diverse physiological functions, some of which are mediated by posttranslational modification. In a mouse model of CKD, we found that a high sulfur amino acid-containing diet resulted in posttranslationally modified microbial tryptophanase activity. This reduced uremic toxin-producing activity and ameliorated progression to CKD in the mice. Thus, diet can tune microbiota function to support healthy host physiology through posttranslational modification without altering microbial community composition.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Diet
  • Dietary Proteins / metabolism*
  • Disease Models, Animal
  • Disease Progression
  • Escherichia coli / enzymology
  • Escherichia coli / metabolism*
  • Gastrointestinal Microbiome*
  • Hydrogen Sulfide / metabolism
  • Indican / metabolism
  • Kidney / physiology*
  • Mice
  • Protein Processing, Post-Translational*
  • Proteome / metabolism*
  • Renal Insufficiency, Chronic / physiopathology*
  • Toxins, Biological / metabolism
  • Tryptophanase / metabolism*


  • Dietary Proteins
  • Proteome
  • Toxins, Biological
  • Tryptophanase
  • Indican
  • Hydrogen Sulfide