Single Cell Transcriptomics Reveals the Hidden Microbiomes of Human Tissues

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Abstract The human microbiome has been studied extensively across those sites in the body that are readily accessible to sampling. Internal organs and tissues, however, have remained largely unexplored and, in the absence of infectious disease, are widely assumed to be free of microorganisms. Using single-cell transcriptomic data from the Tabula Sapiens spanning 11 human organ donors, 19 tissue types, 400,000+ annotated cells, 100+ cell types, and ∼70 billion sequences, we created an atlas of the human tissue microbiome with cell type resolution across three domains of life which we refer to as the Tabula Sapiens Microbiome. Together with data from 8 additional donors derived from a different set of experimental techniques for validation, we identified sequences from numerous bacterial, viral and fungal species in human tissues. We mapped the likely microbial flow routes in the body from external-facing microbiomes and natural environments to internal tissues and tumors, demonstrating the existence of several unexpected routes. In the case of tumor microbiomes, we find a considerable number of bacterial genera found in tumors are detectable across tumor-free tissues, suggesting that tumor microbiomes are in part sourced from adjacent normal tissues, even those from distant sites. Finally, by increasing the resolution of sampling from tissues to cell types, we quantified the microbial load and diversity across different human cell types to reveal a network of host cell type and microbe associations. For example, we identified traces of both latent and active Epstein Barr Virus infections in various cell types such as splenic plasma cells. Broad exploration of the human tissue microbiomes may provide insights which ultimately are of clinical importance.

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