Spatial host-microbiome sequencing

Mucosal and barrier tissues such as the gut, lung or skin, are composed of a complex network of cells and microbes forming a tight niche that prevents pathogen colonization and supports host-microbiome symbiosis. Characterizing these networks at high molecular and cellular resolution is crucial for our understanding of homeostasis and disease. Spatial transcriptomics has emerged as a key technology to positionally profile RNAs at high resolution in tissues. Here, we present spatial host-microbiome sequencing, an all-sequencing based approach that captures tissue histology, polyadenylated RNAs and bacterial 16S sequences directly from tissues on spatially barcoded glass surfaces. We apply our approach to the mouse gut as a model system, use a novel deep learning approach for data mapping and detect spatial niches impacted by microbial biogeography. Spatial host-microbiome sequencing should enhance study of native host-microbe interactions in health and disease. ### Competing Interest Statement A.R. is a founder and equity holder of Celsius Therapeutics, an equity holder in Immunitas Therapeutics and until August 31, 2020 was a SAB member of Syros Pharmaceuticals, Neogene Therapeutics, Asimov and ThermoFisher Scientific. From August 1, 2020, A.R. is an employee of Genentech, and equity holder in Roche. S.V is an author on patents applied for by Spatial Transcriptomics AB (10X Genomics Inc). S.V. and A.R. are co-inventors on PCT/US2020/015481 relating to this work. The remaining authors declare no competing interests.