Immune homeostasis in the intestinal environment relies on the balanced interplay between various microbiome components, epithelial cells, and immune players. In inflammatory conditions, such as Intestinal Bowel Disease (IBD), functional changes in epithelial, immune, and bacterial cells result in epithelial barrier erosion, triggering acute immune responses in the intestinal tissue.
To map an intricate ecosystem such as the intestine, it is essential to develop technologies that can evaluate host tissue and its respective bacterial components within their spatial context.
Microbiome Cartography (MicroCart) is a framework that facilitates the convergence of host-microbiome interactions and spatial analytic techniques. MicroCart refines 16S rRNA probe design and protocol for precise bacterial taxonomic identification while maintaining the integrity of high-plex biological markers within the tissue. This allows for subsequent multi-parametric analyses on contiguous segments of murine intestinal samples, including spatial proteomics, spatial transcriptomics, and spatial glycomics.
Results:
Iterative spatial omics, a framework that guides research from discovery to mechanistic validation, offers a comprehensive understanding of the tissue microenvironment. Colitis intestines show a comprehensive, yet orderly, reconfiguration of the immune landscape, microbial community dynamics, and metabolic pathway modifications at the tissue level. Using MicroCart with iterative spatial omics, the data show an 1) Increased expression and infiltration of macrophage and monocytic populations, 2) Depletion of plasma cells in the immune-rich regions within the large intestine, 3) upregulation of truncated and immature surface glycans, and 4) a decreased diversity in the local microbiome composition.
This support a model where macrophage and monocyte infiltration acts as a front-line host defense mechanism against bacterial components that have breached the physical epithelial barrier during colitis. These insights underscore the imperative to decode the exact native tissue context of pathological states and their interactive elements to propel future mechanistic and therapeutic explorations.
Impact:
MicroCart allows an in-depth exploration into the nuanced symbiosis between host tissues and their resident microbiomes via spatial multiomics. This platform can be utilized for forthcoming studies aimed at disentangling the complex web of cellular and microbial interactions within the intricate ecosystem of the host-microbe interface.
Figure 1B, Representative images of the intestinal tissue sections that were investigated by the three different modalities. Images from left to right: H&E image of the tissue section; representative MIBI antibody signals from the tissue section; fluorescence image with boxes indicating the regions being captured for transcriptomic analysis in the tissue section of DSP; representative MALDI N-Glycan signals from the tissue section.
