Background and Aims

Pglyrp3 is a bactericidal innate immunity protein known to sustain the habitual gut microbiome and protect against experimental colitis. Intestinal inflammation and metaflammation are commonly associated with a marked reduction of commensal bifidobacteria. Whether Pglyrp3 and bifidobacteria interact synergistically or additively to alleviate metaflammation is unknown. We investigated the extent to which Pglyrp3 and bifidobacteria regulate metaflammation and gut bacterial dysbiosis in DSS-induced mouse models of intestinal inflammation.

Material & Methods

8–10 weeks old male mice were used. In both WT and Pglyrp3 −/− experiments, the mice were randomly divided into three groups of 16 mice per group: (1) a control group receiving sterile tap water, (2) an experimental group receiving sterile tap water supplemented with only 5% DSS, and (3) an experimental group receiving sterile tap water supplemented with 5% DSS and 1 × 10⁹ CFU/ml of Bifidobacterium adolescentis (B.a.) for 7 days. Wild-type (WT) littermates of the respective gene (i.e. Pglyrp3) were used as controls throughout the study. Clinical signs of general health and inflammation were monitored daily. Faecal pellet samples were analysed by qRT-PCR for microbial composition. Histology of relevant organs was carried out on day 8. Metabolic parameters and liver inflammation were determined in serum samples.

Results

Intestinal inflammation in mice of group 2 were significantly increased compared to those of control group 1. There was a significant difference in mean scores for inflammation severity between DSS-treated WT and DSS-treated Pglyrp3 −/− mice. Buildup of key serum metabolic markers (cholesterol, triglyceride and glucose) was set off by colonic inflammation. qRT-PCR quantification showed that DSS significantly decreased the Clostridium coccoides and Bifidobacterium cell counts while increasing those of Bacteroides group in both WT and Pglyrp3 −/− mice. These manifestations of DSS-induced dysbiosis were significantly attenuated by feeding B.a. Both the local and systemic ill-being of the mice alleviated when they received B.a.

Discussion

This study shows that Pglyrp3 facilitates recognition of bifidobacterial cell wall-derived peptidoglycan, thus leading additively to a reduction of metaflammation through an increase in the number of bifidobacteria, which were able to mitigate intestinal immunopathology in the context of Pglyrp3 blockade.

中文翻译：

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PGLYRP3 和青春双歧杆菌 Reuter 1963 对 Pglyrp3 敲除 (Pglyrp3 -/-) 和野生型 (WT) 小鼠 DSS 诱导的结肠炎严重程度的附加保护作用研究

背景和目标

Pglyrp3 是一种杀菌性先天免疫蛋白，已知可维持肠道习惯性微生物群并预防实验性结肠炎。肠道炎症和元炎症通常与共生双歧杆菌的显着减少有关。Pglyrp3 和双歧杆菌是否协同或相加地相互作用以减轻元炎症尚不清楚。我们研究了 Pglyrp3 和双歧杆菌在 DSS 诱导的肠道炎症小鼠模型中调节炎症和肠道细菌失调的程度。

材料与方法

使用了 8-10 周大的雄性小鼠。在 WT 和 Pglyrp3 -/- 实验中，将小鼠随机分为三组，每组 16 只小鼠：(1) 对照组接受无菌自来水，(2) 实验组接受仅添加 5% 的无菌自来水DSS，和 (3) 实验组接受无菌自来水补充 5% DSS 和 1 × 10 ⁹ CFU/ml青春双歧杆菌( Ba) 7 天。相应基因（即Pglyrp3）的野生型（WT）同窝仔在整个研究过程中用作对照。每天监测一般健康和炎症的临床症状。通过 qRT-PCR 分析粪便颗粒样品的微生物组成。在第8天进行相关器官的组织学检查。测定血清样品中的代谢参数和肝脏炎症。

结果

与对照组 1 相比，第 2 组小鼠的肠道炎症显着增加。DSS 处理的 WT 和 DSS 处理的 Pglyrp3 -/- 小鼠之间炎症严重程度的平均评分存在显着差异。结肠炎症引发了关键血清代谢标志物（胆固醇、甘油三酯和葡萄糖）的积累。qRT-PCR 定量显示，DSS在 WT 和 Pglyrp3 -/- 小鼠中显着降低球状芽孢杆菌和双歧杆菌细胞计数，同时增加拟杆菌属组的细胞计数。DSS 诱导的生态失调的这些表现通过喂食Ba显着减弱。小鼠局部和全身不适均在接受治疗后得到缓解巴

讨论

这项研究表明，Pglyrp3 有助于识别双歧杆菌细胞壁衍生的肽聚糖，从而通过增加双歧杆菌的数量来减少元炎症，这能够在 Pglyrp3 阻断的情况下减轻肠道免疫病理学。