Pan Zhe, Chen Yanhong, Zhou Mi, McAllister Tim A, Mcneilly Tom N, Guan Le Luo
Department of Agricultural, Food and Nutritional Science, University of Alberta, Edmonton, AB T6G 2P5, Canada.
Agriculture and Agri-Food Canada, Lethbridge Research Centre, Lethbridge, AB T1J 4B1, Canada.
ISME J. 2024 Jan 8;18(1). doi: 10.1093/ismejo/wrae127.
The rectal-anal junction (RAJ) is the major colonization site of Shiga toxin-producing Escherichia coli (STEC) O157 in beef cattle, leading to transmission of this foodborne pathogen from farms to food chains. To date, there is limited understanding regarding whether the mucosa-attached microbiome has a profound impact on host-STEC interactions. In this study, the active RAJ mucosa-attached microbiota and its potential role in host immunity-STEC commensal interactions were investigated using RAJ mucosal biopsies collected from calves orally challenged with two STEC O157 strains with or without functional stx2a (stx2a+ or stx2a-). The results revealed that shifts of microbial diversity, topology, and assembly patterns were subjected to stx2a production post-challenge and Paeniclostridium and Gallibacterium were the keystone taxa for both microbial interactions and assembly. Additional mucosal transcriptome profiling showed stx2a-dependent host immune responses (i.e. B- and T-cell signaling and antigen processing and presentation) post-challenge. Further integrated analysis revealed that mucosa-attached beneficial microbes (i.e. Provotella, Faecalibacterium, and Dorea) interacted with host immune genes pre-challenge to maintain host homeostasis; however, opportunistic pathogenic microbes (i.e. Paeniclostridium) could interact with host immune genes after the STEC O157 colonization and interactions were stx2a-dependent. Furthermore, predicted bacterial functions involved in pathogen (O157 and Paeniclostridium) colonization and metabolism were related to host immunity. These findings suggest that during pathogen colonization, host-microbe interactions could shift from beneficial to opportunistic pathogenic bacteria driven and be dependent on the production of particular virulence factors, highlighting the potential regulatory role of mucosa-attached microbiota in affecting pathogen-commensal host interactions in calves with STEC O157 infection.
直肠-肛门交界处（RAJ）是产志贺毒素大肠杆菌（STEC）O157在肉牛中的主要定植部位，导致这种食源性病原体从农场传播到食物链。迄今为止，关于黏膜附着微生物群是否对宿主与STEC的相互作用有深远影响，人们了解有限。在本研究中，利用从口服接种两株有或无功能性stx2a（stx2a+或stx2a-）的STEC O157菌株的犊牛采集的RAJ黏膜活检样本，研究了活跃的RAJ黏膜附着微生物群及其在宿主免疫-STEC共生相互作用中的潜在作用。结果显示，挑战后微生物多样性、拓扑结构和组装模式的变化取决于stx2a的产生，而消化链球菌属和加氏菌属是微生物相互作用和组装的关键分类群。额外的黏膜转录组分析显示，挑战后存在stx2a依赖性的宿主免疫反应（即B细胞和T细胞信号传导以及抗原加工和呈递）。进一步的综合分析表明，黏膜附着的有益微生物（即普雷沃菌属、粪杆菌属和多雷亚菌属）在挑战前与宿主免疫基因相互作用以维持宿主内环境稳定；然而，机会性致病微生物（即消化链球菌属）在STEC O157定植后可与宿主免疫基因相互作用，且相互作用取决于stx2a。此外，预测参与病原体（O157和消化链球菌属）定植和代谢的细菌功能与宿主免疫相关。这些发现表明，在病原体定植期间，宿主-微生物相互作用可能从有益细菌驱动转变为机会性致病细菌驱动，并取决于特定毒力因子的产生，突出了黏膜附着微生物群在影响感染STEC O157的犊牛中病原体-共生宿主相互作用方面的潜在调节作用。
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