Giardia duodenalis induces pathogenic dysbiosis of human intestinal microbiota biofilms
Giardia duodenalis induces pathogenic dysbiosis of human intestinal microbiota biofilms
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DOI：
10.1016/j.ijpara.2016.11.010
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发表时间：
2017-05-01
影响因子：
4
通讯作者：
Buret, Andre G.
中科院分区：
文献类型：
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作者：
Beatty, Jennifer K.;Akierman, Sarah V.;Buret, Andre G.
十二指肠贾第虫是世界范围内急性腹泻疾病的普遍病因。然而，最近在意大利和挪威爆发的疫情揭示了贾第虫病与随后发展为慢性感染后肠易激综合征之间的联系。虽然感染后肠易激综合征的致病机制尚不清楚，但最近的研究结果表明，肠道微生物群的改变与肠易激综合征的病理生理有关。在本研究中，我们使用实验室生物膜系统培养和富集来自人类肠道活检的粘膜微生物群。随后，我们发现与贾第鞭毛虫共培养会引起生物膜物种组成和生物膜结构的干扰，导致微生物群落本质上是生态失调的-即使在贾第鞭毛虫被清除后也是如此。这些微生物群异常部分是由分泌-排泄贾第鞭毛虫半胱氨酸蛋白酶介导的。通过体外细胞培养和无菌小鼠感染模型，我们发现贾第鞭毛虫诱导的微生物群破坏促进细菌入侵，导致上皮细胞凋亡、紧密连接破坏和细菌跨肠上皮屏障易位。此外，这些益生菌群群落导致Toll样受体4信号通路的激活增加，并且在人源化无菌小鼠中过度产生促炎细胞因子IL-1 β。先前寻求感染后肠易激综合征发展的解释和危险因素的研究主要集中在肠道病原体的特征和受感染宿主的属性上。我们提出，涉及贾第鞭毛虫和肠道微生物群的多微生物相互作用可能导致持续的生态失调，这为贾第鞭毛虫感染后易患胃肠道疾病的原因提供了新的解释。(C) 2017作者。由Elsevier Ltd代表澳大利亚寄生虫学学会出版。
Giardia duodenalis is a prevalent cause of acute diarrheal disease worldwide. However, recent outbreaks in Italy and Norway have revealed a link between giardiasis and the subsequent development of chronic post-infectious irritable bowel syndrome. While the mechanisms underlying the causation of post infectious irritable bowel syndrome remain obscure, recent findings suggest that alterations in gut micro biota communities are linked to the pathophysiology of irritable bowel syndrome. In the present study, we use a laboratory biofilm system to culture and enrich mucosal microbiota from human intestinal biopsies. Subsequently, we show that co-culture with Giardia induces disturbances in biofilm species composition and biofilm structure resulting in microbiota communities that are intrinsically dysbiotic - even after the clearance of Giardia. These microbiota abnormalities were mediated in part by secretory-excretory Giardia cysteine proteases. Using in vitro cell culture and germ-free murine infection models, we show that Giardia-induced disruptions of microbiota promote bacterial invasion, resulting in epithelial apoptosis, tight junctional disruption, and bacterial translocation across an intestinal epithelial barrier. Additionally, these dysbiotic microbiota communities resulted in increased activation of the Toll like receptor 4 signalling pathway, and overproduction of the pro-inflammatory cytokine IL-1 beta in humanized germ-free mice. Previous studies that have sought explanations and risk factors for the development of post-infectious irritable bowel syndrome have focused on features of enteropathogens and attributes of the infected host. We propose that polymicrobial interactions involving Giardia and gut microbiota may cause persistent dysbiosis, offering a new interpretation of the reasons why those afflicted with giardiasis are predisposed to gastrointestinal disorders post-infection. (C) 2017 The Author(s). Published by Elsevier Ltd on behalf of Australian Society for Parasitology.