美国耶鲁大学Noah W. Palm等研究人员合作发现，宿主-微生物群相互作用组揭示广泛的跨界联系。该项研究成果于2024年3月20日在线发表在《自然》杂志上。

研究人员开发并验证了一种新技术——BASEHIT，该技术可对人类外蛋白质组-微生物组的相互作用进行蛋白质组规模的评估。利用BASEHIT，研究人员揭示了来自不同系统发育和起源组织的519种与人类相关的细菌菌株，与3324种人类外蛋白之间的170多万种潜在相互作用。由此产生的相互作用组揭示了一个广泛的跨界连接网络，其中包括数以千计以前未曾描述过的宿主与微生物之间的相互作用，涉及383种菌株和651种宿主蛋白。该网络中的特定结合模式暗示了潜在的生物逻辑；例如，同种菌株表现出共享的外蛋白结合模式，而单个组织分离物则独特地结合了组织特异性外蛋白。

此外，研究人员还观察到数十种独特的、往往是菌株特异性的相互作用，它们在生态位定植、组织重塑和免疫调节中可能发挥作用，并发现具有不同宿主相互作用特征的菌株在体外与宿主细胞的相互作用，以及在体内对宿主免疫系统的影响各不相同。总之，这些研究揭示了以前未曾探索过的分子水平的宿主-微生物群相互作用，这些相互作用可能是当地微生物对人类健康和疾病产生因果效应的基础。

研究人员表示，与人类密切相关的无数微生物对生理产生了各种不同的影响，但这些影响的分子基础大多仍不为人知。经典病原体通常会入侵宿主组织，并通过与人类细胞外蛋白和分泌蛋白（“外蛋白组”）的相互作用来调节免疫反应。共生微生物也可能通过与宿主外源蛋白的相互作用，促进宿主的生态位定植并塑造宿主生物学。然而，外蛋白组与微生物群之间的直接相互作用在很大程度上仍未被探索。

附：英文原文

Title: A host–microbiota interactome reveals extensive transkingdom connectivity

Author: Sonnert, Nicole D., Rosen, Connor E., Ghazi, Andrew R., Franzosa, Eric A., Duncan-Lowey, Brianna, Gonzlez-Hernndez, Jaime A., Huck, John D., Yang, Yi, Dai, Yile, Rice, Tyler A., Nguyen, Mytien T., Song, Deguang, Cao, Yiyun, Martin, Anjelica L., Bielecka, Agata A., Fischer, Suzanne, Guan, Changhui, Oh, Julia, Huttenhower, Curtis, Ring, Aaron M., Palm, Noah W.

Issue&Volume: 2024-03-20

Abstract: The myriad microorganisms that live in close association with humans have diverse effects on physiology, yet the molecular bases for these impacts remain mostly unknown1,2,3. Classical pathogens often invade host tissues and modulate immune responses through interactions with human extracellular and secreted proteins (the ‘exoproteome’). Commensal microorganisms may also facilitate niche colonization and shape host biology by engaging host exoproteins; however, direct exoproteome–microbiota interactions remain largely unexplored. Here we developed and validated a novel technology, BASEHIT, that enables proteome-scale assessment of human exoproteome–microbiome interactions. Using BASEHIT, we interrogated more than 1.7 million potential interactions between 519 human-associated bacterial strains from diverse phylogenies and tissues of origin and 3,324 human exoproteins. The resulting interactome revealed an extensive network of transkingdom connectivity consisting of thousands of previously undescribed host–microorganism interactions involving 383 strains and 651 host proteins. Specific binding patterns within this network implied underlying biological logic; for example, conspecific strains exhibited shared exoprotein-binding patterns, and individual tissue isolates uniquely bound tissue-specific exoproteins. Furthermore, we observed dozens of unique and often strain-specific interactions with potential roles in niche colonization, tissue remodelling and immunomodulation, and found that strains with differing host interaction profiles had divergent interactions with host cells in vitro and effects on the host immune system in vivo. Overall, these studies expose a previously unexplored landscape of molecular-level host–microbiota interactions that may underlie causal effects of indigenous microorganisms on human health and disease.

DOI: 10.1038/s41586-024-07162-0

Source: https://www.nature.com/articles/s41586-024-07162-0