IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v15y2024i1d10.1038_s41467-024-50807-x.html
   My bibliography  Save this article

Harnessing intestinal tryptophan catabolism to relieve atherosclerosis in mice

Author

Listed:
  • Mouna Chajadine

    (PARCC)

  • Ludivine Laurans

    (PARCC)

  • Tobias Radecke

    (PARCC)

  • Nirmala Mouttoulingam

    (PARCC)

  • Rida Al-Rifai

    (PARCC)

  • Emilie Bacquer

    (PARCC)

  • Clara Delaroque

    (INSERM U1306
    Université Paris Cité)

  • Héloïse Rytter

    (INSERM U1306
    Université Paris Cité)

  • Marius Bredon

    (Gastroenterology Department
    Paris Centre for Microbiome Medicine (PaCeMM) FHU)

  • Camille Knosp

    (PARCC)

  • José Vilar

    (PARCC)

  • Coralie Fontaine

    (Université de Toulouse)

  • Nadine Suffee

    (PARCC)

  • Marie Vandestienne

    (PARCC)

  • Bruno Esposito

    (PARCC)

  • Julien Dairou

    (Laboratoire de Chimie et de Biochimie Pharmacologiques et Toxicologiques)

  • Jean Marie Launay

    (Hôpital Lariboisière)

  • Jacques Callebert

    (Hôpital Lariboisière)

  • Alain Tedgui

    (PARCC)

  • Hafid Ait-Oufella

    (PARCC)

  • Harry Sokol

    (Gastroenterology Department
    Paris Centre for Microbiome Medicine (PaCeMM) FHU
    Micalis institute)

  • Benoit Chassaing

    (INSERM U1306
    Université Paris Cité)

  • Soraya Taleb

    (PARCC)

Abstract

Tryptophan (Trp) is an essential amino acid, whose metabolism is a key gatekeeper of intestinal homeostasis. Yet, its systemic effects, particularly on atherosclerosis, remain unknown. Here we show that high-fat diet (HFD) increases the activity of intestinal indoleamine 2, 3-dioxygenase 1 (IDO), which shifts Trp metabolism from the production of microbiota-derived indole metabolites towards kynurenine production. Under HFD, the specific deletion of IDO in intestinal epithelial cells leads to intestinal inflammation, impaired intestinal barrier, augmented lesional T lymphocytes and atherosclerosis. This is associated with an increase in serotonin production and a decrease in indole metabolites, thus hijacking Trp for the serotonin pathway. Inhibition of intestinal serotonin production or supplementation with indole derivatives alleviates plaque inflammation and atherosclerosis. In summary, we uncover a pivotal role of intestinal IDO in the fine-tuning of Trp metabolism with systemic effects on atherosclerosis, paving the way for new therapeutic strategies to relieve gut-associated inflammatory diseases.

Suggested Citation

  • Mouna Chajadine & Ludivine Laurans & Tobias Radecke & Nirmala Mouttoulingam & Rida Al-Rifai & Emilie Bacquer & Clara Delaroque & Héloïse Rytter & Marius Bredon & Camille Knosp & José Vilar & Coralie F, 2024. "Harnessing intestinal tryptophan catabolism to relieve atherosclerosis in mice," Nature Communications, Nature, vol. 15(1), pages 1-16, December.
  • Handle: RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-50807-x
    DOI: 10.1038/s41467-024-50807-x
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41467-024-50807-x
    File Function: Abstract
    Download Restriction: no

    File URL: https://libkey.io/10.1038/s41467-024-50807-x?utm_source=ideas
    LibKey link: if access is restricted and if your library uses this service, LibKey will redirect you to where you can use your library subscription to access this item
    ---><---

    References listed on IDEAS

    as
    1. Tatsuo Hashimoto & Thomas Perlot & Ateequr Rehman & Jean Trichereau & Hiroaki Ishiguro & Magdalena Paolino & Verena Sigl & Toshikatsu Hanada & Reiko Hanada & Simone Lipinski & Birgit Wild & Simone M. , 2012. "ACE2 links amino acid malnutrition to microbial ecology and intestinal inflammation," Nature, Nature, vol. 487(7408), pages 477-481, July.
    2. Henrik M. Roager & Tine R. Licht, 2018. "Microbial tryptophan catabolites in health and disease," Nature Communications, Nature, vol. 9(1), pages 1-10, December.
    3. Chris Schiering & Emma Wincent & Amina Metidji & Andrea Iseppon & Ying Li & Alexandre J. Potocnik & Sara Omenetti & Colin J. Henderson & C. Roland Wolf & Daniel W. Nebert & Brigitta Stockinger, 2017. "Feedback control of AHR signalling regulates intestinal immunity," Nature, Nature, vol. 542(7640), pages 242-245, February.
    Full references (including those not matched with items on IDEAS)

    Most related items

    These are the items that most often cite the same works as this one and are cited by the same works as this one.
    1. Giorgia Renga & Fiorella D’Onofrio & Marilena Pariano & Roberta Galarini & Carolina Barola & Claudia Stincardini & Marina M. Bellet & Helmut Ellemunter & Cornelia Lass-Flörl & Claudio Costantini & Val, 2023. "Bridging of host-microbiota tryptophan partitioning by the serotonin pathway in fungal pneumonia," Nature Communications, Nature, vol. 14(1), pages 1-21, December.
    2. Guanlan Hu & Catriona Ling & Lijun Chi & Mehakpreet K. Thind & Samuel Furse & Albert Koulman & Jonathan R. Swann & Dorothy Lee & Marjolein M. Calon & Celine Bourdon & Christian J. Versloot & Barbara M, 2022. "The role of the tryptophan-NAD + pathway in a mouse model of severe malnutrition induced liver dysfunction," Nature Communications, Nature, vol. 13(1), pages 1-16, December.
    3. Kathleen Shah & Muralidhara Rao Maradana & M. Joaquina Delàs & Amina Metidji & Frederike Graelmann & Miriam Llorian & Probir Chakravarty & Ying Li & Mauro Tolaini & Michael Shapiro & Gavin Kelly & Chr, 2022. "Cell-intrinsic Aryl Hydrocarbon Receptor signalling is required for the resolution of injury-induced colonic stem cells," Nature Communications, Nature, vol. 13(1), pages 1-16, December.
    4. Nguyen T. Van & Karen Zhang & Rachel M. Wigmore & Anne I. Kennedy & Carolina R. DaSilva & Jialing Huang & Manju Ambelil & Jose H. Villagomez & Gerald J. O’Connor & Randy S. Longman & Miao Cao & Adam E, 2023. "Dietary L-Tryptophan consumption determines the number of colonic regulatory T cells and susceptibility to colitis via GPR15," Nature Communications, Nature, vol. 14(1), pages 1-15, December.
    5. Paolo Manghi & Michele Filosi & Moreno Zolfo & Lucas G. Casten & Albert Garcia-Valiente & Stefania Mattevi & Vitor Heidrich & Davide Golzato & Samuel Perini & Andrew M. Thomas & Simone Montalbano & Sa, 2024. "Large-scale metagenomic analysis of oral microbiomes reveals markers for autism spectrum disorders," Nature Communications, Nature, vol. 15(1), pages 1-18, December.
    6. Yan-Xin Zhang & Xin Yang & Pan Zou & Peng-Fei Du & Jing Wang & Fen Jin & Mao-Jun Jin & Yong-Xin She, 2016. "Nonylphenol Toxicity Evaluation and Discovery of Biomarkers in Rat Urine by a Metabolomics Strategy through HPLC-QTOF-MS," IJERPH, MDPI, vol. 13(5), pages 1-17, May.
    7. Kirsty Brown & Carolyn A. Thomson & Soren Wacker & Marija Drikic & Ryan Groves & Vina Fan & Ian A. Lewis & Kathy D. McCoy, 2023. "Microbiota alters the metabolome in an age- and sex- dependent manner in mice," Nature Communications, Nature, vol. 14(1), pages 1-12, December.
    8. Marta G. Novelle, 2021. "Decoding the Role of Gut-Microbiome in the Food Addiction Paradigm," IJERPH, MDPI, vol. 18(13), pages 1-19, June.
    9. Xiuchuan (Lucas) Hu & Wenfeng Xiao & Yuxian Lei & Adam Green & Xinyi Lee & Muralidhara Rao Maradana & Yajing Gao & Xueru Xie & Rui Wang & George Chennell & M. Albert Basson & Pete Kille & Wolfgang Mar, 2023. "Aryl hydrocarbon receptor utilises cellular zinc signals to maintain the gut epithelial barrier," Nature Communications, Nature, vol. 14(1), pages 1-15, December.

    More about this item

    Statistics

    Access and download statistics

    Corrections

    All material on this site has been provided by the respective publishers and authors. You can help correct errors and omissions. When requesting a correction, please mention this item's handle: RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-50807-x. See general information about how to correct material in RePEc.

    If you have authored this item and are not yet registered with RePEc, we encourage you to do it here. This allows to link your profile to this item. It also allows you to accept potential citations to this item that we are uncertain about.

    If CitEc recognized a bibliographic reference but did not link an item in RePEc to it, you can help with this form .

    If you know of missing items citing this one, you can help us creating those links by adding the relevant references in the same way as above, for each refering item. If you are a registered author of this item, you may also want to check the "citations" tab in your RePEc Author Service profile, as there may be some citations waiting for confirmation.

    For technical questions regarding this item, or to correct its authors, title, abstract, bibliographic or download information, contact: Sonal Shukla or Springer Nature Abstracting and Indexing (email available below). General contact details of provider: http://www.nature.com .

    Please note that corrections may take a couple of weeks to filter through the various RePEc services.

    IDEAS is a RePEc service. RePEc uses bibliographic data supplied by the respective publishers.