Nag Dhrubajyoti, Farr Dustin, Raychaudhuri Saumya, Withey Jeffrey H
Department of Biochemistry, Microbiology, and Immunology, Wayne State University School of Medicine, Detroit, MI, USA.
CSIR-Institute of Microbial Technology, Sector 39A, Chandigarh 160036, India.
iScience. 2022 Jun 9;25(7):104572. doi: 10.1016/j.isci.2022.104572. eCollection 2022 Jul 15.
Adherent-invasive (AIEC) is an opportunistic pathogen associated with major inflammatory bowel disease, Crohn disease, and ulcerative colitis. Unfavorable conditions push commensal AIEC to induce gut inflammation, sometimes progressing to inflammation-induced colon cancer. Recently, zebrafish have emerged as a useful model to study human intestinal pathogens. Here, a zebrafish model to study AIEC infection was developed. Bath inoculation with AIEC resulted in colonization and tissue disruption in the zebrafish intestine. Gene expression of pro-inflammatory markers including interleukin-1β (IL-1β), tumor necrosis factor alpha (TNFα), interferon-γ (IFNγ), and S100A-10b (akin to human calprotectin) in the zebrafish intestine was significantly induced by AIEC infection. The probiotic Nissle 1917 (EcN) was tested as a therapeutic and prophylactic against AIEC infection and reduced AIEC colonization, tissue damage, and pro-inflammatory responses in zebrafish. Furthermore, EcN diminished the propionic-acid-augmented hyperinfection of AIEC in zebrafish. Thus, this study shows the efficacy of EcN against AIEC in an AIEC-zebrafish model.
黏附侵袭性大肠杆菌（AIEC）是一种与主要炎症性肠病、克罗恩病和溃疡性结肠炎相关的机会致病菌。不利条件促使共生AIEC引发肠道炎症，有时会发展为炎症诱导的结肠癌。最近，斑马鱼已成为研究人类肠道病原体的有用模型。在此，开发了一种用于研究AIEC感染的斑马鱼模型。用AIEC进行浸浴接种导致斑马鱼肠道定植和组织破坏。AIEC感染显著诱导了斑马鱼肠道中促炎标志物的基因表达，包括白细胞介素-1β（IL-1β）、肿瘤坏死因子α（TNFα）、干扰素-γ（IFNγ）和S100A-10b（类似于人类钙卫蛋白）。益生菌Nissle 1917（EcN）作为针对AIEC感染的治疗和预防药物进行了测试，它减少了斑马鱼体内AIEC的定植、组织损伤和促炎反应。此外，EcN减少了丙酸增强的斑马鱼AIEC过度感染。因此，本研究表明在AIEC-斑马鱼模型中EcN对AIEC具有疗效。
