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 Gut microbes mediate the metabolism of sulfur-containing amino acids in the host diet to modulate production of uremic toxins. 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.

中文翻译：

---

饮食翻译后修饰小鼠肠道微生物蛋白质组以调节肾功能

微生物群保护肾脏 慢性肾病 (CKD) 困扰着全球数百万人。慢性肾病的一线治疗是饮食干预，因此可能存在与肠道微生物群相关的成分。洛贝尔等人。研究了微生物群和蛋白质摄入之间的机制联系，因为蛋白质代谢物吲哚和硫酸吲哚酚是已知的尿毒症毒素（参见 Pluznick 的观点）。作者使用了因饮食中缺乏含硫氨基酸蛋氨酸和半胱氨酸而诱发慢性肾病的小鼠模型。含硫氨基酸的细菌代谢通过色氨酸酶的硫化物抑制来调节吲哚的产生，从而消除该模型系统中该代谢物的尿毒症毒性。科学，本期第 14 页。1518; 另见 p. 1426 肠道微生物介导宿主饮食中含硫氨基酸的代谢，以调节尿毒症毒素的产生。慢性肾病（CKD）与肠道微生物群之间的关联已被假设，但其潜在机制仍存在疑问。在人类中，膳食蛋白质会增加肠道细菌产生硫化氢 (H2S)、吲哚和硫酸吲哚酚。后者是尿毒症毒素，H2S具有多种生理功能，其中一些是通过翻译后修饰介导的。在 CKD 小鼠模型中，我们发现含高硫氨基酸的饮食会导致微生物色氨酸酶活性发生翻译后修饰。这降低了小鼠尿毒症毒素的产生活性并改善了 CKD 的进展。因此，饮食可以通过翻译后修饰来调整微生物群功能，以支持健康的宿主生理机能，而不改变微生物群落的组成。