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

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Science  18 Sep 2020:
Vol. 369, Issue 6510, pp. 1518-1524
DOI: 10.1126/science.abb3763

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Microbiota protect the kidneys

Chronic kidney disease (CKD) afflicts millions of people globally. The first-line treatment for CKD is dietary intervention, so there may be a gut microbiota–associated component. Lobel et al. investigated the mechanistic links between the microbiota and protein intake, because the protein metabolites indole and indoxyl sulfate are known uremic toxins (see the Perspective by Pluznick). The authors used a mouse model of CKD precipitated by a paucity of the dietary sulfur–containing amino acids methionine and cysteine. Bacterial metabolism of sulfur-containing amino acids modulated indole production by sulfide inhibition of the enzyme tryptophanase, thus abrogating uremic toxicity by this metabolite in this model system.

Science, this issue p. 1518; see also p. 1426

Abstract

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.

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