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Benefits of equilibrium between microbiota- and host-derived ligands of the aryl hydrocarbon receptor after stroke in aged male mice

Author

Listed:
  • Pedram Peesh

    (The University of Texas McGovern Medical School
    The University of Texas MD Anderson UTHealth Graduate School of Biomedical Sciences
    The University of Texas McGovern Medical School)

  • Maria P. Blasco-Conesa

    (The University of Texas McGovern Medical School)

  • Ahmad El Hamamy

    (The University of Texas McGovern Medical School)

  • Romeesa Khan

    (The University of Texas McGovern Medical School)

  • Gary U. Guzman

    (The University of Texas McGovern Medical School)

  • Parisa Honarpisheh

    (The University of Texas McGovern Medical School)

  • Eric C. Mohan

    (The University of Texas McGovern Medical School)

  • Grant W. Goodman

    (The University of Texas McGovern Medical School)

  • Justin N. Nguyen

    (The University of Texas McGovern Medical School)

  • Anik Banerjee

    (The University of Texas McGovern Medical School
    The University of Texas MD Anderson UTHealth Graduate School of Biomedical Sciences)

  • Bryce E. West

    (The University of Texas McGovern Medical School)

  • Kyung Ae Ko

    (The University of Texas McGovern Medical School)

  • Janelle M. Korf

    (The University of Texas McGovern Medical School
    The University of Texas MD Anderson UTHealth Graduate School of Biomedical Sciences)

  • Chunfeng Tan

    (The University of Texas McGovern Medical School)

  • Huihui Fan

    (The University of Texas McGovern Medical School)

  • Gabriela D. Colpo

    (The University of Texas McGovern Medical School)

  • Hilda Ahnstedt

    (The University of Texas McGovern Medical School)

  • Lucy Couture

    (The University of Texas McGovern Medical School)

  • Solji Roh

    (The University of Texas McGovern Medical School)

  • Julia K. Kofler

    (University of Pittsburgh School of Medicine)

  • Jose F. Moruno-Manchon

    (The University of Texas McGovern Medical School)

  • Michael E. Maniskas

    (The University of Texas McGovern Medical School)

  • Jaroslaw Aronowski

    (The University of Texas McGovern Medical School)

  • Rodney M. Ritzel

    (The University of Texas McGovern Medical School)

  • Juneyoung Lee

    (The University of Texas McGovern Medical School)

  • Jun Li

    (The University of Texas McGovern Medical School)

  • Robert M. Bryan

    (Department of Anesthesiology)

  • Anjali Chauhan

    (The University of Texas McGovern Medical School)

  • Venugopal Reddy Venna

    (The University of Texas McGovern Medical School)

  • Louise D. McCullough

    (The University of Texas McGovern Medical School)

  • Bhanu Priya Ganesh

    (The University of Texas McGovern Medical School
    The University of Texas MD Anderson UTHealth Graduate School of Biomedical Sciences)

Abstract

Recent studies have highlighted the crucial role of microglia (MG) and their interactions with the gut microbiome in post-stroke neuroinflammation. The activation of immunoregulatory pathways, including the aryl hydrocarbon receptor (AHR) pathway, is influenced by a dynamic balance of ligands derived from both the host and microbiota. This study aimed to investigate the association between stroke-induced dysbiosis and the resultant imbalance in AHR ligand sources (loss of microbiota-derived [indole-based] and increase of host-derived [kynurenine-based]) after stroke. Microbiota-derived AHR ligands decreased in human plasma and remained low for days following an ischemic stroke highlighting the translational significance. Transient-middle-cerebral-artery-occlusion was performed in aged wild-type and germ-free male mice. MG-AHR expression and activity increased in both in vivo and ex vivo stroke models. Germ-free mice showed altered neuroinflammation and antigen presentation while aged mice showed reduced infarct volume and neurological deficits following treatment with microbiota-derived AHR ligands after stroke. Restoring a balanced pool of host- and microbiota-derived AHR ligands may be beneficial after stroke and may represent a therapeutic target.

Suggested Citation

  • Pedram Peesh & Maria P. Blasco-Conesa & Ahmad El Hamamy & Romeesa Khan & Gary U. Guzman & Parisa Honarpisheh & Eric C. Mohan & Grant W. Goodman & Justin N. Nguyen & Anik Banerjee & Bryce E. West & Kyu, 2025. "Benefits of equilibrium between microbiota- and host-derived ligands of the aryl hydrocarbon receptor after stroke in aged male mice," Nature Communications, Nature, vol. 16(1), pages 1-16, December.
    • Handle: RePEc:nat:natcom:v:16:y:2025:i:1:d:10.1038_s41467-025-57014-2
    DOI: 10.1038/s41467-025-57014-2
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    References listed on IDEAS

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    1. Henrik M. Roager & Tine R. Licht, 2018. "Microbial tryptophan catabolites in health and disease," Nature Communications, Nature, vol. 9(1), pages 1-10, December.
    2. Veit Rothhammer & Davis M. Borucki & Emily C. Tjon & Maisa C. Takenaka & Chun-Cheih Chao & Alberto Ardura-Fabregat & Kalil Alves de Lima & Cristina Gutiérrez-Vázquez & Patrick Hewson & Ori Staszewski , 2018. "Microglial control of astrocytes in response to microbial metabolites," Nature, Nature, vol. 557(7707), pages 724-728, May.
    3. Yuuki Obata & Álvaro Castaño & Stefan Boeing & Ana Carina Bon-Frauches & Candice Fung & Todd Fallesen & Mercedes Gomez Agüero & Bahtiyar Yilmaz & Rita Lopes & Almaz Huseynova & Stuart Horswell & Mural, 2020. "Neuronal programming by microbiota regulates intestinal physiology," Nature, Nature, vol. 578(7794), pages 284-289, February.
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