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A multi-omics spatial framework for host-microbiome dissection within the intestinal tissue microenvironment

Author

Listed:
  • Bokai Zhu

    (Ragon Institute of MGH, MIT, and Harvard
    Broad Institute of MIT and Harvard
    Stanford University)

  • Yunhao Bai

    (Broad Institute of MIT and Harvard
    Stanford University)

  • Yao Yu Yeo

    (Harvard Medical School)

  • Xiaowei Lu

    (Stanford University)

  • Xavier Rovira-Clavé

    (Stanford University
    Barcelona Institute of Science and Technology (BIST))

  • Han Chen

    (Stanford University
    UCSF)

  • Jason Yeung

    (Harvard Medical School)

  • Dingani Nkosi

    (Massachusetts General Brigham)

  • Jonathan Glickman

    (Massachusetts General Brigham)

  • Antonio Delgado-Gonzalez

    (Stanford University)

  • Georg K. Gerber

    (Harvard Medical School
    Harvard University and MIT)

  • Mike Angelo

    (Stanford University)

  • Alex K. Shalek

    (Ragon Institute of MGH, MIT, and Harvard
    Broad Institute of MIT and Harvard
    Massachusetts Institute of Technology
    Massachusetts Institute of Technology)

  • Garry P. Nolan

    (Stanford University)

  • Sizun Jiang

    (Broad Institute of MIT and Harvard
    Harvard Medical School
    Harvard Medical School
    Harvard Medical School)

Abstract

The intricate interactions between the host immune system and its microbiome constituents undergo dynamic shifts in response to perturbations to the intestinal tissue environment. Our ability to study these events on the systems level is significantly limited by in situ approaches capable of generating simultaneous insights from both host and microbial communities. Here, we introduce Microbiome Cartography (MicroCart), a framework for simultaneous in situ probing of host and microbiome across multiple spatial modalities. We demonstrate MicroCart by investigating gut host and microbiome changes in a murine colitis model, using spatial proteomics, transcriptomics, and glycomics. Our findings reveal a global but systematic transformation in tissue immune responses, encompassing tissue-level remodeling in response to host immune and epithelial cell state perturbations, bacterial population shifts, localized inflammatory responses, and metabolic process alterations during colitis. MicroCart enables a deep investigation of the intricate interplay between the host tissue and its microbiome with spatial multi-omics.

Suggested Citation

  • Bokai Zhu & Yunhao Bai & Yao Yu Yeo & Xiaowei Lu & Xavier Rovira-Clavé & Han Chen & Jason Yeung & Dingani Nkosi & Jonathan Glickman & Antonio Delgado-Gonzalez & Georg K. Gerber & Mike Angelo & Alex K., 2025. "A multi-omics spatial framework for host-microbiome dissection within the intestinal tissue microenvironment," Nature Communications, Nature, vol. 16(1), pages 1-20, December.
    • Handle: RePEc:nat:natcom:v:16:y:2025:i:1:d:10.1038_s41467-025-56237-7
    DOI: 10.1038/s41467-025-56237-7
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