Department of Biology, Center for Inflammation, Immunity, and Infection, Georgia State University, Atlanta, Georgia, USA.
Department of Microbiology and Department of Molecular Biology and Genetics, Cornell University, Ithaca, New York, USA.
Gut. 2014 Jul;63(7):1069-80. doi: 10.1136/gutjnl-2013-304909. Epub 2013 Jul 29.
Inflammatory bowel disease (IBD) is driven by a seemingly aberrant immune response to the gut microbiota with disease development dictated by genetics and environmental factors. A model exemplifying this notion is our recent demonstration that colonisation of adherent-invasive Escherichia coli (AIEC) during microbiota acquisition drove chronic colitis in mice lacking the flagellin receptor TLR5 (T5KO). T5KO colitis persisted beyond AIEC clearance and requires TLR4 and the NLRC4 inflammasome. We hypothesised that AIEC instigates chronic inflammation by increasing microbial lipopolysaccharide (LPS) and flagellin levels.
Examine if transient AIEC colonisation lastingly alters levels of LPS and flagellin and changes microbiota composition.
Germ-free mice (wild type (WT) and T5KO) were inoculated with AIEC strain LF82 and placed in standard housing allowing a complex microbiota that eliminated AIEC in both mice strains. Faeces were assayed for the inflammatory marker, lipocalin-2, bacterial loads, and microbiota composition by pyrosequencing. Faecal LPS and flagellin bioactivity were measured via a cell-based reporter assay.
Transient AIEC colonisation, in WT mice, did not alter inflammatory markers, bacterial loads, microbiota composition, nor its pro-inflammatory potential. By contrast, transient AIEC colonisation of T5KO mice drove chronic inflammation which correlated with microbiota components having higher levels of bioactive LPS and flagellin. Such AIEC-induced elevation of LPS and flagellin persisted well beyond AIEC clearance, required AIEC be flagellated, and was associated with alteration in microbiota species composition including a loss of species diversity.
AIEC, and perhaps other pathobionts, may instigate chronic inflammation in susceptible hosts by altering the gut microbiota composition so as to give it an inherently greater ability to activate innate immunity/pro-inflammatory gene expression.
炎症性肠病（IBD）是由对肠道微生物群的异常免疫反应驱动的，疾病的发展取决于遗传和环境因素。我们最近的研究证明了这一观点，即在获得微生物群的过程中定植黏附侵袭性大肠杆菌（AIEC）会驱动缺乏鞭毛受体 TLR5（T5KO）的小鼠发生慢性结肠炎，这一模型表明，AIEC 定植会导致慢性炎症，这是由于微生物脂多糖（LPS）和鞭毛蛋白水平增加。
检查 AIEC 的短暂定植是否会持久改变 LPS 和鞭毛蛋白水平，并改变微生物群落组成。
无菌（野生型（WT）和 T5KO）小鼠用 AIEC 菌株 LF82 接种，并放置在标准饲养环境中，使复杂的微生物群能够消除两种小鼠品系中的 AIEC。通过焦磷酸测序检测粪便中的炎症标志物脂联素-2、细菌负荷和微生物群落组成。通过基于细胞的报告基因测定法测量粪便 LPS 和鞭毛蛋白的生物活性。
在 WT 小鼠中，AIEC 的短暂定植不会改变炎症标志物、细菌负荷、微生物群落组成或其促炎潜能。相比之下，T5KO 小鼠的 AIEC 短暂定植会导致慢性炎症，这与微生物群落成分具有更高水平的生物活性 LPS 和鞭毛蛋白相关。这种 AIEC 诱导的 LPS 和鞭毛蛋白升高在 AIEC 清除后仍持续存在，需要 AIEC 具有鞭毛结构，并且与微生物物种组成的改变相关，包括物种多样性的丧失。
AIEC，也许还有其他条件致病菌，可能通过改变肠道微生物群落组成，从而使其固有地更有能力激活先天免疫/促炎基因表达，在易感宿主中引发慢性炎症。
