High Resolution Spatial Mapping of Microbiome-Host Interactions via in situ Polyadenylation and Spatial RNA Sequencing

Ntekas, I.; Takayasu, L.; McKellar, D. W.; Grodner, B. M.; Holdener, C.; Schweitzer, P. A.; Sauthoff, M.; Shi, Q.; Brito, I. L.; De Vlaminck, I.

doi:10.1101/2024.11.18.624127

bioRxiv · 10.1101/2024.11.18.624127

High Resolution Spatial Mapping of Microbiome-Host Interactions via in situ Polyadenylation and Spatial RNA Sequencing

Ntekas, I.·Takayasu, L.·McKellar, D. W.·Grodner, B. M.·Holdener, C.·Schweitzer, P. A.·Sauthoff, M.·Shi, Q.·Brito, I. L.·De Vlaminck, I.

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Abstract

Inter-microbial and host-microbial interactions are thought to be critical for the functioning of the gut microbiome, but few tools are available to measure these interactions. Here, we report a method for unbiased spatial sampling of microbiome-host interactions in the gut at one micron resolution. This method combines enzymatic in situ polyadenylation of both bacterial and host RNA with spatial RNA-sequencing. Application of this method in a mouse model of intestinal neoplasia revealed the biogeography of the mouse gut microbiome as function of location in the intestine, frequent strong inter-microbial interactions at short length scales, shaping of local microbiome niches by the host, and tumor-associated changes in the architecture of the host-microbiome interface. This method is compatible with broadly available commercial platforms for spatial RNA-sequencing, and can therefore be readily adopted to broadly study the role of short-range, bidirectional host-microbe interactions in microbiome health and disease.

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Ntekas, I., Takayasu, L., McKellar, D. W., Grodner, B. M., Holdener, C., Schweitzer, P. A., Sauthoff, M., Shi, Q., Brito, I. L., De Vlaminck, I.. 2024-11-18. High Resolution Spatial Mapping of Microbiome-Host Interactions via in situ Polyadenylation and Spatial RNA Sequencing. https://doi.org/10.1101/2024.11.18.624127

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