IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v14y2023i1d10.1038_s41467-023-38950-3.html
   My bibliography  Save this article

A probiotic bi-functional peptidoglycan hydrolase sheds NOD2 ligands to regulate gut homeostasis in female mice

Author

Listed:
  • Jie Gao

    (Southern Medical University)

  • Lei Wang

    (Southern Medical University)

  • Jing Jiang

    (Sichuan Academy of Medical Sciences & Sichuan Provincial People’s Hospital)

  • Qian Xu

    (Southern Medical University)

  • Nianyi Zeng

    (Southern Medical University)

  • Bingyun Lu

    (Southern Medical University)

  • Peibo Yuan

    (Southern Medical University)

  • Kai Sun

    (Southern Medical University)

  • Hongwei Zhou

    (Southern Medical University
    Southern Medical University)

  • Xiaolong He

    (Southern Medical University)

Abstract

Secreted proteins are one of the direct molecular mechanisms by which microbiota influence the host, thus constituting a promising field for drug discovery. Here, through bioinformatics-guided screening of the secretome of clinically established probiotics from Lactobacillus, we identify an uncharacterized secreted protein (named LPH here) that is shared by most of these probiotic strains (8/10) and demonstrate that it protects female mice from colitis in multiple models. Functional studies show that LPH is a bi-functional peptidoglycan hydrolase with both N-Acetyl-β-D-muramidase and DL-endopeptidase activities that can generate muramyl dipeptide (MDP), a NOD2 ligand. Different active site mutants of LPH in combination with Nod2 knockout female mice confirm that LPH exerts anti-colitis effects through MDP-NOD2 signaling. Furthermore, we validate that LPH can also exert protective effects on inflammation-associated colorectal cancer in female mice. Our study reports a probiotic enzyme that enhances NOD2 signaling in vivo in female mice and describes a molecular mechanism that may contribute to the effects of traditional Lactobacillus probiotics.

Suggested Citation

  • Jie Gao & Lei Wang & Jing Jiang & Qian Xu & Nianyi Zeng & Bingyun Lu & Peibo Yuan & Kai Sun & Hongwei Zhou & Xiaolong He, 2023. "A probiotic bi-functional peptidoglycan hydrolase sheds NOD2 ligands to regulate gut homeostasis in female mice," Nature Communications, Nature, vol. 14(1), pages 1-15, December.
  • Handle: RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-38950-3
    DOI: 10.1038/s41467-023-38950-3
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41467-023-38950-3
    File Function: Abstract
    Download Restriction: no

    File URL: https://libkey.io/10.1038/s41467-023-38950-3?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. Shikha Nayar & Joshua K. Morrison & Mamta Giri & Kyle Gettler & Ling-shiang Chuang & Laura A. Walker & Huaibin M. Ko & Ephraim Kenigsberg & Subra Kugathasan & Miriam Merad & Jaime Chu & Judy H. Cho, 2021. "A myeloid–stromal niche and gp130 rescue in NOD2-driven Crohn’s disease," Nature, Nature, vol. 593(7858), pages 275-281, May.
    2. Pinaki Panigrahi & Sailajanandan Parida & Nimai C. Nanda & Radhanath Satpathy & Lingaraj Pradhan & Dinesh S. Chandel & Lorena Baccaglini & Arjit Mohapatra & Subhranshu S. Mohapatra & Pravas R. Misra &, 2017. "A randomized synbiotic trial to prevent sepsis among infants in rural India," Nature, Nature, vol. 548(7668), pages 407-412, August.
    3. Bianca Lungu & Ovidiu Georgescu & Beatrice Tudor & Roxana Buzan & Manuela Grijincu & Monica Cotarca & Carmen Panaitescu & Kuan-Wei Chen & Iuliu Torda & Calin Mircu & Ioan Hutu, 2022. "Study of some factors associated with polyclonal antibody production in rabbit," Eximia Journal, Plus Communication Consulting SRL, vol. 4(1), pages 14-18, April.
    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. Riley D. Metcalfe & Eric Hanssen & Ka Yee Fung & Kaheina Aizel & Clara C. Kosasih & Courtney O. Zlatic & Larissa Doughty & Craig J. Morton & Andrew P. Leis & Michael W. Parker & Paul R. Gooley & Tracy, 2023. "Structures of the interleukin 11 signalling complex reveal gp130 dynamics and the inhibitory mechanism of a cytokine variant," Nature Communications, Nature, vol. 14(1), pages 1-18, December.
    2. Egle Kvedaraite & Magda Lourda & Natalia Mouratidou & Tim Düking & Avinash Padhi & Kirsten Moll & Paulo Czarnewski & Indranil Sinha & Ioanna Xagoraris & Efthymia Kokkinou & Anastasios Damdimopoulos & , 2024. "Intestinal stroma guides monocyte differentiation to macrophages through GM-CSF," Nature Communications, Nature, vol. 15(1), pages 1-16, December.
    3. Fengfei Wu & Fangting Wu & Qian Zhou & Xi Liu & Jieying Fei & Da Zhang & Weidong Wang & Yi Tao & Yubing Lin & Qiaoqiao Lin & Xinghua Pan & Kai Sun & Fang Xie & Lan Bai, 2023. "A CCL2+DPP4+ subset of mesenchymal stem cells expedites aberrant formation of creeping fat in humans," Nature Communications, Nature, vol. 14(1), pages 1-16, December.
    4. Johannes Haushofer & Michael Kremer & Ricardo Maertens & Brandon Joel Tan, 2021. "Water Treatment and Child Mortality: Evidence from Kenya," NBER Working Papers 29447, National Bureau of Economic Research, Inc.
    5. Aamer Imdad & Faseeha Rehman & Evans Davis & Deepika Ranjit & Gamael S. S. Surin & Suzanna L. Attia & Sarah Lawler & Abigail A. Smith & Zulfiqar A. Bhutta, 2021. "Effects of neonatal nutrition interventions on neonatal mortality and child health and development outcomes: A systematic review," Campbell Systematic Reviews, John Wiley & Sons, vol. 17(1), March.

    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:14:y:2023:i:1:d:10.1038_s41467-023-38950-3. 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.