宏基因组多态性毒素效应物和免疫谱分析可预测微生物组发育及疾病相关的生态失调。

Metagenomic polymorphic toxin effector and immunity profiling predicts microbiome development and disease-related dysbiosis.

作者信息

Schroer Hunter W, Beghini Francesco, Garay Juan Antonio Raygoza, Christakis Nicholas A, Bosch Dustin E

机构信息

Civil, Architectural & Environmental Engineering, Missouri University of Science and Technology, Rolla, MO.

Yale Institute for Network Science, Yale University, New Haven, CT.

出版信息

bioRxiv. 2025 Jul 8:2025.07.08.662037. doi: 10.1101/2025.07.08.662037.

Abstract

Bacteria use antagonistic interbacterial weapons such as polymorphic toxin secretion systems (TSS) to compete for niches in the human gut microbiome. We developed a bioinformatic marker gene approach (PolyProf) to quantify TSS including ~200 effector and immunity genes and applied it to ~15,000 publicly available human metagenomes. PolyProf alpha and beta diversity readily distinguished 12 different human disease states. Decision tree machine learning models integrating bacterial taxonomy with PolyProf had near-perfect accuracy (ROC area 1.00) for all 12 disease states. During microbiome development in the first year of life, PolyProf alpha diversity increases, and beta diversity becomes increasingly like the maternal microbiome, influenced by vertical transfer, delivery mode, and breastfeeding. PolyProf is related to strain sharing among adults through social interactions. In summary, interbacterial antagonism with TSS shapes microbiome development and interpersonal strain sharing. Since PolyProf distinguishes diverse adult disease statuses, these dynamics may contribute to non-genetic inheritance.

摘要

细菌利用多态性毒素分泌系统(TSS)等拮抗细菌武器在人类肠道微生物群中竞争生态位。我们开发了一种生物信息标记基因方法(PolyProf)来量化包括约200个效应基因和免疫基因的TSS,并将其应用于约15000个公开可用的人类宏基因组。PolyProf的α和β多样性能够轻松区分12种不同的人类疾病状态。将细菌分类学与PolyProf相结合的决策树机器学习模型对所有12种疾病状态的预测准确率近乎完美(ROC面积为1.00)。在生命第一年的微生物群发育过程中,PolyProf的α多样性增加,β多样性越来越类似于母体微生物群,这受到垂直传播、分娩方式和母乳喂养的影响。PolyProf与成年人通过社交互动进行的菌株共享有关。总之,TSS介导的细菌间拮抗作用塑造了微生物群的发育和人际间的菌株共享。由于PolyProf能够区分不同的成人疾病状态,这些动态变化可能有助于非遗传继承。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1816/12265584/fad97a458a6a/nihpp-2025.07.08.662037v1-f0001.jpg

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