Background: The 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. Methods: We 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. Results: We 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. Conclusions: Tumor 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.

中文翻译：

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估计肿瘤生长对肿瘤组织微生物组的选择压力

背景：肿瘤与其微生物组之间的关系仍然令人费解，可能存在双向相互作用。肿瘤微生物组一方面可以抑制或刺激肿瘤生长，另一方面也可以抑制或刺激肿瘤生长。另一方面，肿瘤的生长可能对其微生物组施加选择压力。对于双向交互的模式和/或扩展尚未达成共识。本研究的目的是通过与 20 多种癌症类型中实体正常组织对其相应组织微生物组的选择压力进行比较，估计原发肿瘤对肿瘤微生物组的选择压力。方法：我们应用斯隆近中性理论和来自 TCGA（癌症基因组图谱）数据库的肿瘤组织微生物组大数据集来实现上述目标。近中性理论模型可以确定微生物群落中中性以上、中性和中性以下物种的比例，与宿主组织的正选择压力、中性选择压力和负选择压力相对应。通过比较原发肿瘤和实体正常组织之间的比例，我们可以推断肿瘤生长对组织微生物组的选择压力。结果：我们发现实体正常组织微生物组中大约 65% 的物种是中性的，而在原发性肿瘤微生物组中这一比例仅为 40%。相比之下，原发肿瘤微生物组中正选物种的比例超过 60%。此外，中性理论模型的模拟表明，最丰富的物种大多是中性的，而非中性物种位于物种丰度分布的长尾。结论：肿瘤生长对常驻微生物组产生强烈的正选择，导致某些物种的丰度高于中性过程预期的水平。尽管如此，中性物种仍然是最丰富的物种之一，这表明有必要密切关注低丰度或稀有物种，因为它们可能在肿瘤发生中发挥关键作用。