Chen Chien-Chang, Louie Steve, Shi Hai Ning, Walker W Allan
Chang Gung Children's Hospital and Chang Gung University, Taoyuan, Taiwan.
Pediatr Res. 2005 Dec;58(6):1185-91. doi: 10.1203/01.pdr.0000183660.39116.83.
Enteropathogenic Escherichia coli (EPEC) is a common pathogen in infantile diarrhea, causing a characteristic histopathologic attaching and effacing (A/E) lesion in the intestinal mucosa. The mouse pathogen Citrobacter rodentium causes a similar A/E lesion in the murine intestine. Like EPEC, C. rodentium infection results in colonic crypt hyperplasia, goblet cell depletion, epithelial proliferation, and mucosal disruption. Using this murine model, we tested the hypothesis that preinoculation of murine gut with Lactobacillus acidophilus early in life can enhance host defense against enteric bacterial infection and attenuate bacteria-mediated colitis. Two-week old BALB/c mice were inoculated with L. acidophilus twice per week for 4 weeks before C. rodentium infection or concomitantly with the exposure to C. rodentium at 6-8 weeks of age. The probiotics were administered twice weekly thereafter. We observed that L. acidophilus inoculation in mice inhibits C. rodentium-induced colitis, which is associated with a decrease in C. rodentium colonization and translocation, an increase in its clearance, and a suppression of colonic myeloperoxidase (MPO) activity. Probiotic treatment also stimulates regulatory cytokine expression in the colon [transforming growth factor beta (TGF-beta), interleukin (IL)-10]. Preinoculation with L. acidophilus is more effective than concomitant use of probiotics in the induction of intestinal IgA secretion and in the downregulation of proinflammatory cytokine expression [tumor necrosis factor alpha (TNF-alpha), IL-6, and IL-12]. These observations suggest that inoculation with probiotics can effectively prevent bacteria-induced colitis by limiting enteric bacteria infection and promoting mucosal protective regulatory immune responses. This study may have ramifications for prevention of infectious diarrhea in human infants and children, particularly in developing countries.
肠致病性大肠杆菌（EPEC）是婴儿腹泻的常见病原体，可在肠黏膜中引起特征性的组织病理学黏附和抹消（A/E）病变。小鼠病原体鼠柠檬酸杆菌在小鼠肠道中引起类似的A/E病变。与EPEC一样，鼠柠檬酸杆菌感染会导致结肠隐窝增生、杯状细胞减少、上皮细胞增殖和黏膜破坏。利用这个小鼠模型，我们测试了以下假设：在生命早期用嗜酸乳杆菌预先接种小鼠肠道可以增强宿主对肠道细菌感染的防御能力，并减轻细菌介导的结肠炎。两周大的BALB/c小鼠在感染鼠柠檬酸杆菌前每周接种嗜酸乳杆菌两次，共4周，或在6-8周龄时与接触鼠柠檬酸杆菌同时接种。此后每周给益生菌给药两次。我们观察到，小鼠接种嗜酸乳杆菌可抑制鼠柠檬酸杆菌诱导的结肠炎，这与鼠柠檬酸杆菌的定植和易位减少、清除增加以及结肠髓过氧化物酶（MPO）活性的抑制有关。益生菌治疗还刺激结肠中调节性细胞因子的表达[转化生长因子β（TGF-β）、白细胞介素（IL）-10]。在诱导肠道IgA分泌和下调促炎细胞因子表达[肿瘤坏死因子α（TNF-α）、IL-6和IL-12]方面，预先接种嗜酸乳杆菌比同时使用益生菌更有效。这些观察结果表明，接种益生菌可以通过限制肠道细菌感染和促进黏膜保护性调节性免疫反应来有效预防细菌诱导的结肠炎。这项研究可能对预防人类婴幼儿尤其是发展中国家的感染性腹泻有影响。
