ArticleCell chemical biology2023
Mechanism-based inhibition of gut microbial tryptophanases reduces serum indoxyl sulfate.
Article in Cell chemical biology, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers, 1 of them a synthesis that pooled it.
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Who cites it
23 citing papers in PubMed, 1 synthesis or guideline pooled it, 30 citations in OpenAlex.
- Impact of amino acid supplementation on cardiovascular and chronic kidney diseases: a systematic review.Cardiovascular research · 2026Pooled it
- Testosterone administration partially modulates gut microbiota responses to severe energy deficit.American journal of physiology. Endocrinology and metabolism · 2026Trial
- Article
- The microbiome regulates host metabolic health and diseases through microbial enzymes.Nature reviews. Gastroenterology & hepatology · 2026Review
- Integrated transcriptomic and metabolomic analysis reveals potential candidate genes and regulatory pathways associated with egg weight in geese.Poultry science · 2026Article
- Roles of Indole and Its Derivative in ModulatingInternational journal of molecular sciences · 2026Article
- Phenotypic high-throughput screening identifies modulators of gut microbial choline metabolism.mBio · 2026Article
- Chemical-mediated alteration of antibiotic susceptibility: mechanisms and potential new targets for antibiotic adjuvant discovery.Journal of bacteriology · 2026Review
- Lactobacillus acidophilus KBL409 improves serum indoxyl sulfate via gut microbial changes in a human study.NPJ science of food · 2026Article
- Organ cross-talk: molecular mechanisms, biological functions, and therapeutic interventions for diseases.Signal transduction and targeted therapy · 2026Review
- Gut-kidney axis in IgA nephropathy: mechanisms linking microbiota dysbiosis to immune dysregulation, Gd-IgA1 generation, and renal injury.Frontiers in immunology · 2026Review
- A guide to uraemic toxicity.Nature reviews. Nephrology · 2026Review
- Review
- Interplay between gut microbiota and acute kidney injury: a review of their mutual influence and causation.Renal failure · 2025Review
- Exercise and Carnosine Modulate Microbiota-Derived Metabolites, Myokines, and Cardiometabolic Profiles in Rats: A Randomized Controlled Trial.Biomedicines · 2025Article
- Microbiota and kidney disease: the road ahead.Nature reviews. Nephrology · 2025Review
- Type 2 Diabetes and the Multifaceted Gut-X Axes.Nutrients · 2025Review
- Emerging gut microbial glycoside hydrolase inhibitors.RSC chemical biology · 2025Review
- N -Acetyl-Tryptophan in Acute Kidney Injury after Cardiac Surgery.Journal of the American Society of Nephrology : JASN · 2025Article
- Structure and dynamics of Proteus vulgaris tryptophan indole-lyase complexes with l-ethionine and l-alanine.Archives of biochemistry and biophysics · 2025Article
Corrections and comments
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Authors and funding
9 authors at 2 institutions in 1 country.
Funding
Abstract
Indoxyl sulfate is a microbially derived uremic toxin that accumulates in late-stage chronic kidney disease and contributes to both renal and cardiovascular toxicity. Indoxyl sulfate is generated by the metabolism of indole, a compound created solely by gut microbial tryptophanases. Here, we characterize the landscape of tryptophanase enzymes in the human gut microbiome and find remarkable structural and functional similarities across diverse taxa. We leverage this homology through a medicinal chemistry campaign to create a potent pan-inhibitor, (3S) ALG-05, and validate its action as a transition-state analog. (3S) ALG-05 successfully reduces indole production in microbial culture and displays minimal toxicity against microbial and mammalian cells. Mice treated with (3S) ALG-05 show reduced cecal indole and serum indoxyl sulfate levels with minimal changes in other tryptophan-metabolizing pathways. These studies present a non-bactericidal pan-inhibitor of gut microbial tryptophanases with potential promise for reducing indoxyl sulfate in chronic kidney disease.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.