How many microbial species are there in human tumor and normal tissues?

Abstract

AbstractThe study of tissue microbiomes is a recent endeavor in human microbiome research, particularly in the area of blood microbiomes. This is primarily due to their low biomass, which presents inadvertent operational contamination as a significant experimental obstacle. The critical role of the tissue microbiomes in cancer development has brought this topic to the forefront of cancer research. However, a fundamental question regarding the potential biodiversity, as stated in the title, has not been addressed to our knowledge. In this study, we estimate the potential microbial diversity or “dark” biodiversity in human tumor and normal tissues using the Diversify-Area Relationship (DAR) method (Ma 2018, 2019) based on large datasets from TCGA (The Cancer Genome Atlas) database (Pooreet al. 2021). We found that the total species richness (number), typical species equivalents (number), and dominant species equivalents (number) of tumor tissues are approximately 1948, 36, and 22, respectively. Among the total species richness, the proportions of archaea, bacteria, and viruses are about 3%-5%, 78%-79%, and 17%-18%, respectively. Moreover, the tissue species richness is approximately 12.5% of skin microbiomes, and 25% of gut microbiomes. We also found that tumor growth does not significantly influence the global or pan-tumor scale diversity, which means that the previous numbers also represent the potential microbial diversity of human tissues, including blood. On a local or single cancer-type scale, tumors may influence the potential diversity in approximately 5% of cases. We hypothesize that, globally, local diversity variations would offset each other.Lay SummaryThis study focused on microbiomes - the tiny microbes that live in our tissues, especially blood. Studying them is challenging due to their low biomass and risk of contamination. Microbiomes may play a key role in cancer, but their diversity within tissues remains unclear. Using diversity-area relationship modeling with data from “The Cancer Genome Atlas” database, we estimated the potential microbial diversity of human tumor and normal tissues. We found approximately 1,948 microbial species in tumors, comprising archaea (5%), bacteria (78%) and viruses (17%). However, dominant or common microbial species number only about two to three dozen. Tissue microbe diversity was 12.5% of that found in skin microbiomes and 25% of gut microbiomes. Tumor growth did not significantly impact overall diversity. Therefore, the previous diversity numbers also represent the microbiome diversity of general human tissues and blood. However, some cancer types may affect it locally. While local diversity changes can occur, globally these variations between tissues likely balance out.