A multi-omics spatial framework for host-microbiome dissection within the intestinal tissue microenvironment PMID: 39890778

Target-related Cytokines

2026-09-23

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

Nat Commun. 2025 Jan 31;16(1):1230. doi: 10.1038/s41467-025-56237-7.

Bokai Zhu ¹ ² ³ , Yunhao Bai ² ³ , Yao Yu Yeo ⁴ , Xiaowei Lu ⁵ , Xavier Rovira-Clavé ³ ⁶ , Han Chen ³ ⁷ , Jason Yeung ⁴ , Dingani Nkosi ⁸ , Jonathan Glickman ⁸ , Antonio Delgado-Gonzalez ³ , Georg K Gerber ⁹ ¹⁰ , Mike Angelo ¹¹ , Alex K Shalek ¹ ² ¹² ¹³ ¹⁴ , Garry P Nolan ¹⁵ , Sizun Jiang ¹⁶ ¹⁷ ¹⁸ ¹⁹

Affiliations

1. Ragon Institute of MGH, MIT, and Harvard, Cambridge, MA, USA.
2. Broad Institute of MIT and Harvard, Cambridge, MA, USA.
3. Department of Microbiology and Immunology, Stanford University, Stanford, CA, USA.
4. Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA.
5. Mass Spectrometry Core Facility, Stanford University, Stanford, CA, USA.
6. Institute for Bioengineering of Catalonia (IBEC), Barcelona Institute of Science and Technology (BIST), Barcelona, Spain.
7. Biological and Medical Informatics Program, UCSF, San Francisco, CA, USA.
8. Department of Pathology, Massachusetts General Brigham, Boston, MA, USA.
9. Division of Computational Pathology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
10. Health Sciences and Technology, Harvard University and MIT, Cambridge, MA, USA.
11. Department of Pathology, Stanford University, Stanford, CA, USA.
12. Institute for Medical Engineering and Science, Massachusetts Institute of Technology, Cambridge, MA, USA.
13. Department of Chemistry, Massachusetts Institute of Technology, Cambridge, MA, USA.
14. Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA, USA.
15. Department of Pathology, Stanford University, Stanford, CA, USA. [email protected].
16. Broad Institute of MIT and Harvard, Cambridge, MA, USA. [email protected].
17. Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA. [email protected].
18. Division of Computational Pathology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA. [email protected].
19. Department of Microbiology, Harvard Medical School, Boston, MA, USA. [email protected].

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.