Your browser doesn't support javascript.
loading
Gut bacterial isoamylamine promotes age-related cognitive dysfunction by promoting microglial cell death.
Teng, Yun; Mu, Jingyao; Xu, Fangyi; Zhang, Xiangcheng; Sriwastva, Mukesh K; Liu, Qiaohong M; Li, Xiaohong; Lei, Chao; Sundaram, Kumaran; Hu, Xin; Zhang, Lifeng; Park, Juw Won; Hwang, Jae Yeon; Rouchka, Eric C; Zhang, Xiang; Yan, Jun; Merchant, Michael L; Zhang, Huang-Ge.
Afiliación
  • Teng Y; Brown Cancer Center, University of Louisville, Louisville, KY 40202, USA. Electronic address: yun.teng@louisville.edu.
  • Mu J; Brown Cancer Center, University of Louisville, Louisville, KY 40202, USA.
  • Xu F; Brown Cancer Center, University of Louisville, Louisville, KY 40202, USA.
  • Zhang X; Brown Cancer Center, University of Louisville, Louisville, KY 40202, USA; Department of ICU, The Affiliated Huaian No. 1 People's Hospital of Nanjing Medical University, Huaian, Jiangsu 223300, China.
  • Sriwastva MK; Brown Cancer Center, University of Louisville, Louisville, KY 40202, USA.
  • Liu QM; Peak Neuromonitoring Associates-Kentucky, Louisville, KY 40202, USA.
  • Li X; Department of Anatomical Sciences and Neurobiology, University of Louisville, Louisville, KY 40202, USA; Kentucky IDeA Network of Biomedical Research Excellence Bioinformatics Core, University of Louisville, Louisville, KY 40202, USA.
  • Lei C; Brown Cancer Center, University of Louisville, Louisville, KY 40202, USA.
  • Sundaram K; Brown Cancer Center, University of Louisville, Louisville, KY 40202, USA.
  • Hu X; Department of Genomic Medicine, University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
  • Zhang L; Brown Cancer Center, University of Louisville, Louisville, KY 40202, USA.
  • Park JW; Department of Computer Science and Engineering, University of Louisville, Louisville, KY 40202, USA; Kentucky IDeA Network of Biomedical Research Excellence Bioinformatics Core, University of Louisville, Louisville, KY 40202, USA.
  • Hwang JY; Department of Computer Science and Engineering, University of Louisville, Louisville, KY 40202, USA.
  • Rouchka EC; Department of Computer Science and Engineering, University of Louisville, Louisville, KY 40202, USA; Kentucky IDeA Network of Biomedical Research Excellence Bioinformatics Core, University of Louisville, Louisville, KY 40202, USA.
  • Zhang X; Department of Pharmacology and Toxicology, University of Louisville, Louisville, KY 40202, USA.
  • Yan J; Brown Cancer Center, University of Louisville, Louisville, KY 40202, USA.
  • Merchant ML; Kidney Disease Program and Clinical Proteomics Center, University of Louisville, Louisville, KY, USA.
  • Zhang HG; Robley Rex Veterans Affairs Medical Center, Louisville, KY 40206, USA; Brown Cancer Center, University of Louisville, Louisville, KY 40202, USA; Department of Microbiology & Immunology, University of Louisville, Louisville, KY 40202, USA. Electronic address: h0zhan17@louisville.edu.
Cell Host Microbe ; 30(7): 944-960.e8, 2022 07 13.
Article en En | MEDLINE | ID: mdl-35654045
The intestinal microbiome releases a plethora of small molecules. Here, we show that the Ruminococcaceae metabolite isoamylamine (IAA) is enriched in aged mice and elderly people, whereas Ruminococcaceae phages, belonging to the Myoviridae family, are reduced. Young mice orally administered IAA show cognitive decline, whereas Myoviridae phage administration reduces IAA levels. Mechanistically, IAA promotes apoptosis of microglial cells by recruiting the transcriptional regulator p53 to the S100A8 promoter region. Specifically, IAA recognizes and binds the S100A8 promoter region to facilitate the unwinding of its self-complementary hairpin structure, thereby subsequently enabling p53 to access the S100A8 promoter and enhance S100A8 expression. Thus, our findings provide evidence that small molecules released from the gut microbiome can directly bind genomic DNA and act as transcriptional coregulators by recruiting transcription factors. These findings further unveil a molecular mechanism that connects gut metabolism to gene expression in the brain with implications for disease development.
Asunto(s)
Palabras clave
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Bacteriófagos / Disfunción Cognitiva / Microbioma Gastrointestinal Límite: Animals / Humans Idioma: En Revista: Cell Host Microbe Asunto de la revista: MICROBIOLOGIA Año: 2022 Tipo del documento: Article Pais de publicación: Estados Unidos
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Bacteriófagos / Disfunción Cognitiva / Microbioma Gastrointestinal Límite: Animals / Humans Idioma: En Revista: Cell Host Microbe Asunto de la revista: MICROBIOLOGIA Año: 2022 Tipo del documento: Article Pais de publicación: Estados Unidos