C57Bl6 (B6) mice devoid of glutathione peroxidases 1 and 2 (Gpx1/2‐DKO) develop ileitis after weaning. We previously showed germ‐free Gpx1/2‐DKO mice of mixed B6.129 background did not develop ileocolitis. Here, we examine the composition of the ileitis provoking microbiota in B6 Gpx1/2‐DKO mice. DNA was isolated from the ileum fecal stream and subjected to high‐throughput sequencing of the V3 and V4 regions of the 16S rRNA gene to determine the abundance of operational taxonomic units (OTUs). We analyzed the role of bacteria by comparing the microbiomes of the DKO and pathology‐free non‐DKO mice. Mice were treated with metronidazole, streptomycin, and vancomycin to alter pathology and correlate the OTU abundances with pathology levels. Principal component analysis based on Jaccard distance of abundance showed 3 distinct outcomes relative to the source Gpx1/2‐DKO microbiome. Association analyses of pathology and abundance of OTUs served to rule out 7–11 of 24 OTUs for involvement in the ileitis. Collections of OTUs were identified that appeared to be linked to ileitis in this animal model and would be classified as commensals. In Gpx1/2‐DKO mice, host oxidant generation from NOX1 and DUOX2 in response to commensals may compromise the ileum epithelial barrier, a role generally ascribed to oxidants generated from mitochondria, NOX2 and endoplasmic reticulum stress in response to presumptive pathogens in IBD. Elevated oxidant levels may contribute to epithelial cell shedding, which is strongly associated with progress toward inflammation in Gpx1/2‐DKO mice and predictive of relapse in IBD by allowing leakage of microbial components into the submucosa.

中文翻译：

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微生物群在炎症性肠病-谷胱甘肽过氧化物同工酶1和2双敲除小鼠C57BL背景上的回肠炎中的作用。

不含谷胱甘肽过氧化物酶1和2（Gpx1 / 2-DKO）的C57B16（B6）小鼠在断奶后发生回肠炎。我们先前显示混合B6.129背景的无菌Gpx1 / 2-DKO小鼠没有发展回肠结肠炎。在这里，我们检查了B6 Gpx1 / 2-DKO小鼠中引起菌群的回肠炎的成分。从回肠粪便流中分离DNA，并对16S rRNA基因的V3和V4区进行高通量测序，以确定操作分类单位（OTU）的丰度。我们通过比较DKO和无病理学的非DKO小鼠的微生物组来分析细菌的作用。用甲硝唑，链霉素和万古霉素治疗小鼠，以改变病理并将OTU丰度与病理水平相关联。基于Jaccard丰度距离的主成分分析显示，相对于来源Gpx1 / 2-DKO微生物组，有3个不同的结果。OTU的病理学和丰富度的关联分析有助于排除24个OTU中有7-11个回肠炎。在该动物模型中鉴定出似乎与回肠炎有关的OTU的集合，并被归类为共鸣。在Gpx1 / 2-DKO小鼠中，NOX1和DUOX2响应共性产生宿主氧化剂可能会损害回肠上皮屏障，这通常归因于线粒体，NOX2和内质网应激产生的氧化剂，响应IBD中的病原体。氧化剂水平升高可能会导致上皮细胞脱落，