Department of Microbiology, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand.
Department of Microbiology, Faculty of Science, Burapha University, Chonburi, Thailand.
PLoS One. 2024 Nov 15;19(11):e0309106. doi: 10.1371/journal.pone.0309106. eCollection 2024.
The impact of Pseudomonas aeruginosa (PA) was explored in a mouse model with non-diarrheal gut permeability defect using 1.5% dextran sulfate solution (DSS) plus antibiotics (ATB) with or without orally administered PA. As such, ATB+DSS+PA mice induced more severe intestinal injury as indicated by stool consistency and leaky gut (FITC-dextran assay, bacteremia, and endotoxemia) with an increase in serum cytokines, liver enzyme, and hepatocyte apoptosis when compared with ATB+DSS mice. There was no abnormality by these parameters in the non-DSS group, including water alone (control), antibiotics alone (ATB+water), and antibiotics with PA (ATB+water+PA). Despite a similarly fecal microbiome patterns between ATB+DSS and ATB+DSS+PA groups, a higher abundance of Pseudomonas, Enterococci, and Escherichia-Shigella was detected in ATB+DSS+PA mice. Additionally, the additive pro-inflammation between pathogen molecules, using heat-killed P. aeruginosa preparations, and LPS against enterocytes (Caco2) and hepatocytes (HegG2), as indicated by supernatant IL-8 and expression of several genes (IL-8, NF-kB, and NOS2) are demonstrated. In conclusion, presence of P. aeruginosa in the gut exacerbated DSS-induced intestinal injury with spontaneous translocation of LPS and bacteria from the gut into the blood circulation (leaky gut) that induced more severe systemic inflammation. The presence of pathogenic bacteria, especially PA in stool of the healthy individuals might have some adverse effect. More studies are in needed.
本研究采用 1.5%葡聚糖硫酸钠（DSS）联合抗生素（ATB）建立非腹泻型肠道通透性缺陷小鼠模型，探索铜绿假单胞菌（PA）的作用。结果表明，与 ATB+DSS 组相比，联合给予口服 PA 的 ATB+DSS+PA 组小鼠粪便稠度和肠道通透性（FITC-葡聚糖检测、菌血症和内毒素血症）更严重，血清细胞因子、肝酶和肝细胞凋亡增加。非 DSS 组（包括仅饮用水[对照]、仅给予抗生素[ATB+水]和给予抗生素+PA[ATB+水+PA]）无上述参数异常。尽管 ATB+DSS 组和 ATB+DSS+PA 组粪便微生物群模式相似，但 ATB+DSS+PA 组中假单胞菌、肠球菌和大肠埃希氏菌-志贺氏菌的丰度更高。此外，使用热灭活铜绿假单胞菌制剂和 LPS 处理肠上皮细胞（Caco2）和肝细胞（HegG2），可检测到病原体分子之间的炎症增强作用，上清液中 IL-8 和几个基因（IL-8、NF-kB 和 NOS2）的表达增加。结论：肠道中 PA 的存在加重了 DSS 诱导的肠道损伤，导致 LPS 和细菌从肠道自发易位至血液循环（肠道通透性增加），引起更严重的全身炎症。健康个体粪便中存在病原菌，尤其是 PA，可能具有某些不良影响。需要更多的研究。
