Contributions from: Jeffrey Moffitt, @drmingyaoli.bsky.social, Qing Nie, Kazumasa Kanemaru, Sarah Teichmann, Daniel Dar, @ltkagohara.bsky.social, Shalev Itzkovitz, Roser Vento-Tormo, @fertiglab.bsky.social, @fabiantheis.bsky.social

Mitosis?

Thank you Micha! 🙏

We believe our approach marks a paradigm shift in microbiome science, integrating spatial context to uncover how the host interacts with the microbiome at relevant scales. Reach out if you want to try it yourselves

Finally, we explore a vignette of host-microbe interaction in a tumor-bearing tissue section, revealing microbial invasion into the host, possibly because misplaced mucus-producing cells leave the tissue unprotected, enabling generalized host-microbe interaction.

What excites me most: the achieved micron resolution lets us measure colony sizes for individual taxa, potentially linking them to their in vivo growth rates.
The cherry on top? We can identify colocalizing taxa and capture not just rRNA but also microbial genes!

Regarding the host, we retrieve both coding and non-coding signatures along the crypt-villus axis.
We observe high and diverse expression at villus tips, high % unspliced molecules near crypts, and high non-coding RNA percentages closer to the gut wall

Combining in situ polyadenylation with the StereoSeq platform, we reconstruct detailed maps of both cell types and microbial taxa at micron resolution, unlocking unprecedented insights into host-microbe interaction

Using Visium with in situ polyadenylation we explore microbial niches across the transverse and longitudinal axes of the GI

We first tested whether in situ polyadenylation enhances recovery of microbiome-derived RNA at low spatial resolution.
Applying our method across murine gut sections, we observed up to a 100-fold enrichment in microbial RNA while preserving host gene expression.

Building on previous work from @dwmckellar.bsky.social
, we combine a single enzymatic step of in situ polyadenylation with commercial spatial transcriptomics platforms—Visium and StereoSeq—to map host gene expression and microbiome in mouse gut tissue sections

Previous methods to map the interface, like imaging-based HiPR-FISH from our lab and sequencing-based with modified arrays like those developed by the Vickovic and Giacomello labs, capture target microbes but limit unbiased discovery or produce low-resolution maps.
Here we address these challenges.