Persistent gut barrier damage and commensal bacterial influx following eradication of Giardia infection in mice.
Persistent gut barrier damage and commensal bacterial influx following eradication of Giardia infection in mice.
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DOI：
10.1186/1757-4749-5-26
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发表时间：
2013-08-30
期刊：
影响因子：
4.2
通讯作者：
Yu LC
中科院分区：
文献类型：
--
作者：
Chen TL;Chen S;Wu HW;Lee TC;Lu YZ;Wu LL;Ni YH;Sun CH;Yu WH;Buret AG;Yu LC
最近对贾第虫暴发的研究表明，40-80%的感染患者在寄生虫清除后会出现长期功能性胃肠道疾病。我们的目的是评估贾第虫感染后清除阶段肠道屏障和肠道细菌空间分布的变化。小鼠口胃接种G.蓝氏虫滋养体（菌株GS/M）或用盐水成对喂养，并在感染后（PI）第7天（定殖期）和第35天（清除后期）处死。肠上皮屏障功能进行了评估，通过蛋白质印迹的occludin切割和管腔serum大分子渗透性。肠道相关，浅表粘附，粘膜内吞细菌琼脂培养进行了测量，并进行了检查，荧光原位杂交。从分离的粘膜细胞培养的细胞内细菌的特征在于通过16 S rDNA测序。嗜中性粒细胞特异性酯酶染色，髓过氧化物酶活性测定和酶联免疫吸附测定细胞因子浓度用于验证肠组织炎症。在PI第7天和第35天，在贾第虫感染小鼠的肠粘膜中检测到紧密连接损伤。虽然肠道细菌过度生长仅在寄生虫定植期间（PI第7天）是明显的，但在PI第7天和第35天观察到细菌的粘膜粘附和内吞作用增强。多种细菌菌株，包括芽孢杆菌属、乳酸杆菌属、葡萄球菌属和苯基杆菌属，在感染后阶段穿透肠粘膜。PI第7天和第35天，粘膜细菌流入与中性粒细胞浸润和髓过氧化物酶活性增加一致。在PI第35天还检测到肠道IFNγ、TNFα和IL-1β水平升高。贾第虫感染的小鼠在寄生虫清除后表现出持续的紧密连接损伤和细菌渗透，伴有粘膜炎症。这些新的发现表明，由于上皮屏障受损，宿主对其自身微生物群的未解决的免疫反应可能部分导致感染后肠道疾病的发展。
Recent studies of Giardia lamblia outbreaks have indicated that 40–80% of infected patients experience long-lasting functional gastrointestinal disorders after parasitic clearance. Our aim was to assess changes in the intestinal barrier and spatial distribution of commensal bacteria in the post-clearance phase of Giardia infection. Mice were orogastrically inoculated with G. lamblia trophozoites (strain GS/M) or pair-fed with saline and were sacrificed on post-infective (PI) days 7 (colonization phase) and 35 (post-clearance phase). Gut epithelial barrier function was assessed by Western blotting for occludin cleavage and luminal-to-serosal macromolecular permeability. Gut-associated, superficial adherent, and mucosal endocytosed bacteria were measured by agar culturing and were examined by fluorescence in situ hybridization. Intracellular bacteria cultured from isolated mucosal cells were characterized by 16S rDNA sequencing. Neutrophil-specific esterase staining, a myeloperoxidase activity assay, and enzyme-linked immunosorbent assays for cytokine concentrations were used to verify intestinal tissue inflammation. Tight junctional damage was detected in the intestinal mucosa of Giardia-infected mice on PI days 7 and 35. Although intestinal bacterial overgrowth was evident only during parasite colonization (PI day 7), enhanced mucosal adherence and endocytosis of bacteria were observed on PI days 7 and 35. Multiple bacterial strains, including Bacillus, Lactobacillus, Staphylococcus, and Phenylobacterium, penetrated the gut mucosa in the post-infective phase. The mucosal influx of bacteria coincided with increases in neutrophil infiltration and myeloperoxidase activity on PI days 7 and 35. Elevated intestinal IFNγ, TNFα, and IL-1β levels also were detected on PI day 35. Giardia-infected mice showed persistent tight junctional damage and bacterial penetration, accompanied by mucosal inflammation, after parasite clearance. These novel findings suggest that the host’s unresolved immune reactions toward its own microbiota, due to an impaired epithelial barrier, may partly contribute to the development of post-infective gut disorders.
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影响因子：
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作者：
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