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Two distinct gut microbial pathways contribute to meta-organismal production of phenylacetylglutamine with links to cardiovascular disease.
Zhu, Yijun; Dwidar, Mohammed; Nemet, Ina; Buffa, Jennifer A; Sangwan, Naseer; Li, Xinmin S; Anderson, James T; Romano, Kymberleigh A; Fu, Xiaoming; Funabashi, Masanori; Wang, Zeneng; Keranahalli, Pooja; Battle, Shawna; Tittle, Aaron N; Hajjar, Adeline M; Gogonea, Valentin; Fischbach, Michael A; DiDonato, Joseph A; Hazen, Stanley L.
Afiliação
  • Zhu Y; Department of Cardiovascular & Metabolic Sciences, Lerner Research Institute, Cleveland Clinic, Cleveland, OH, USA; Center for Microbiome and Human Health, Cleveland Clinic, Cleveland, OH, USA.
  • Dwidar M; Department of Cardiovascular & Metabolic Sciences, Lerner Research Institute, Cleveland Clinic, Cleveland, OH, USA; Center for Microbiome and Human Health, Cleveland Clinic, Cleveland, OH, USA.
  • Nemet I; Department of Cardiovascular & Metabolic Sciences, Lerner Research Institute, Cleveland Clinic, Cleveland, OH, USA; Center for Microbiome and Human Health, Cleveland Clinic, Cleveland, OH, USA.
  • Buffa JA; Department of Cardiovascular & Metabolic Sciences, Lerner Research Institute, Cleveland Clinic, Cleveland, OH, USA; Center for Microbiome and Human Health, Cleveland Clinic, Cleveland, OH, USA.
  • Sangwan N; Department of Cardiovascular & Metabolic Sciences, Lerner Research Institute, Cleveland Clinic, Cleveland, OH, USA; Center for Microbiome and Human Health, Cleveland Clinic, Cleveland, OH, USA.
  • Li XS; Department of Cardiovascular & Metabolic Sciences, Lerner Research Institute, Cleveland Clinic, Cleveland, OH, USA; Center for Microbiome and Human Health, Cleveland Clinic, Cleveland, OH, USA.
  • Anderson JT; Department of Cardiovascular & Metabolic Sciences, Lerner Research Institute, Cleveland Clinic, Cleveland, OH, USA; Center for Microbiome and Human Health, Cleveland Clinic, Cleveland, OH, USA.
  • Romano KA; Department of Cardiovascular & Metabolic Sciences, Lerner Research Institute, Cleveland Clinic, Cleveland, OH, USA; Center for Microbiome and Human Health, Cleveland Clinic, Cleveland, OH, USA.
  • Fu X; Department of Cardiovascular & Metabolic Sciences, Lerner Research Institute, Cleveland Clinic, Cleveland, OH, USA; Center for Microbiome and Human Health, Cleveland Clinic, Cleveland, OH, USA.
  • Funabashi M; Department of Bioengineering and ChEM-H, Stanford University, Stanford, CA, USA.
  • Wang Z; Department of Cardiovascular & Metabolic Sciences, Lerner Research Institute, Cleveland Clinic, Cleveland, OH, USA; Center for Microbiome and Human Health, Cleveland Clinic, Cleveland, OH, USA.
  • Keranahalli P; Department of Cardiovascular & Metabolic Sciences, Lerner Research Institute, Cleveland Clinic, Cleveland, OH, USA; Case Western Reserve University, College of Arts and Sciences, Cleveland, OH, USA.
  • Battle S; Department of Cardiovascular & Metabolic Sciences, Lerner Research Institute, Cleveland Clinic, Cleveland, OH, USA.
  • Tittle AN; Department of Cardiovascular & Metabolic Sciences, Lerner Research Institute, Cleveland Clinic, Cleveland, OH, USA; Center for Microbiome and Human Health, Cleveland Clinic, Cleveland, OH, USA.
  • Hajjar AM; Department of Cardiovascular & Metabolic Sciences, Lerner Research Institute, Cleveland Clinic, Cleveland, OH, USA; Center for Microbiome and Human Health, Cleveland Clinic, Cleveland, OH, USA.
  • Gogonea V; Department of Chemistry, Cleveland State University, Cleveland, OH, USA.
  • Fischbach MA; Department of Bioengineering and ChEM-H, Stanford University, Stanford, CA, USA.
  • DiDonato JA; Department of Cardiovascular & Metabolic Sciences, Lerner Research Institute, Cleveland Clinic, Cleveland, OH, USA; Center for Microbiome and Human Health, Cleveland Clinic, Cleveland, OH, USA.
  • Hazen SL; Department of Cardiovascular & Metabolic Sciences, Lerner Research Institute, Cleveland Clinic, Cleveland, OH, USA; Center for Microbiome and Human Health, Cleveland Clinic, Cleveland, OH, USA; Department of Cardiovascular Medicine, Heart, Vascular and Thoracic Institute, Cleveland Clinic, Cleve
Cell Host Microbe ; 31(1): 18-32.e9, 2023 01 11.
Article em En | MEDLINE | ID: mdl-36549300
ABSTRACT
Recent studies show gut microbiota-dependent metabolism of dietary phenylalanine into phenylacetic acid (PAA) is critical in phenylacetylglutamine (PAGln) production, a metabolite linked to atherosclerotic cardiovascular disease (ASCVD). Accordingly, microbial enzymes involved in this transformation are of interest. Using genetic manipulation in selected microbes and monocolonization experiments in gnotobiotic mice, we identify two distinct gut microbial pathways for PAA formation; one is catalyzed by phenylpyruvateferredoxin oxidoreductase (PPFOR) and the other by phenylpyruvate decarboxylase (PPDC). PPFOR and PPDC play key roles in gut bacterial PAA production via oxidative and non-oxidative phenylpyruvate decarboxylation, respectively. Metagenomic analyses revealed a significantly higher abundance of both pathways in gut microbiomes of ASCVD patients compared with controls. The present studies show a role for these two divergent microbial catalytic strategies in the meta-organismal production of PAGln. Given the numerous links between PAGln and ASCVD, these findings will assist future efforts to therapeutically target PAGln formation in vivo.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Doenças Cardiovasculares / Microbioma Gastrointestinal Tipo de estudo: Prognostic_studies Limite: Animals Idioma: En Revista: Cell Host Microbe Assunto da revista: MICROBIOLOGIA Ano de publicação: 2023 Tipo de documento: Article País de afiliação: Estados Unidos
Texto completo
Imprimir
XML
PubMed Links
Buscar no Google

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Doenças Cardiovasculares / Microbioma Gastrointestinal Tipo de estudo: Prognostic_studies Limite: Animals Idioma: En Revista: Cell Host Microbe Assunto da revista: MICROBIOLOGIA Ano de publicação: 2023 Tipo de documento: Article País de afiliação: Estados Unidos