Estimating the selection pressure of tumor growth on tumor tissue microbiomes

Abstract

AbstractBackgroundThe relationships between tumor and its microbiome are still puzzling, with possible bidirectional interactions. Tumor microbiomes may suppress or stimulate tumor growth on the one hand; on the other hand, tumor growth may exert selection pressure on its microbiomes. There is not any consensus on the mode and/or extension of the bidirectional interactions. The objective of this study is to estimate the selection pressure from the primary tumors on tumor microbiomes by comparing with the selection pressure from the solid normal tissues on their corresponding tissue microbiomes across 20+ cancer types.MethodsWe apply Sloan near neutral theory and big datasets of tumor tissue microbiomes from the TCGA (The Cancer Genome Atlas) databases to achieve the above objective. The near neutral theory model can determine the proportions of above-neutral, neutral and below-neutral species in microbial communities, corresponding with positive, neutral and negative selection pressures from host tissues. By comparing the proportions between the primary tumors and solid normal tissues, we can infer the selection pressure of tumor growth on tissue microbiomes.ResultsWe find that approximately 65% of species in solid normal tissue microbiomes are neutral, and the proportion is only 40% in the primary tumor microbiomes. In contrast, the proportion of positively selected species exceeds 60% in the primary tumor microbiomes. Furthermore, simulations with neutral theory model reveal that most abundant species are mostly neutral, while non-neutral species are in the long tail of the species abundance distributions.ConclusionsTumor growth exerts strong positive selection on resident microbiomes, driving the abundances of certain species above the levels expected by the neutral process. Nevertheless, neutral species are still among the most abundant species, suggesting the necessity to pay close attention to the low-abundance or rare species because they are likely to play a critical role in oncogenesis.