Department of Infectious Disease Control, Faculty of Medicine, Oita University, Yufu, Oita, Japan.
Department of Gastroenterology, Faculty of Medicine, Oita University, Yufu, Oita, Japan.
PLoS One. 2022 Jun 15;17(6):e0269698. doi: 10.1371/journal.pone.0269698. eCollection 2022.
Antibiotics disrupt normal gut microbiota and cause dysbiosis, leading to a reduction in intestinal epithelial barrier function. Disruption of the intestinal epithelial barrier, which is known as "leaky gut", results in increased intestinal permeability and contributes to the development or exacerbation of gastrointestinal diseases such as inflammatory bowel disease and irritable bowel syndrome. We have previously reported on a murine model of intestinal epithelial barrier dysfunction associated with dysbiosis induced by the administration of ampicillin and vancomycin. Saireito, a traditional Japanese herbal medicine, is often used to treat autoimmune disorders including ulcerative colitis; the possible mechanism of action and its efficacy, however, remains unclear. In this study, we examined the efficacy of Saireito in our animal model for leaky gut associated with dysbiosis. C57BL/6 mice were fed a Saireito diet for the entirety of the protocol (day1-28). To induce colitis, ampicillin and vancomycin were administered in drinking water for the last seven consecutive days (day22-28). As previously demonstrated, treatment with antibiotics caused fecal occult bleeding, cecum enlargement with black discoloration, colon inflammation with epithelial cell apoptosis, and upregulation of pro-inflammatory cytokines. Oral administration of Saireito significantly improved antibiotics-induced fecal occult bleeding and cecum enlargement by suppressing inflammation in the colon. Furthermore, Saireito treatment ensured the integrity of the intestinal epithelial barrier by suppressing apoptosis and inducing cell adhesion proteins including ZO-1, occludin, and E-cadherin in intestinal epithelial cells, which in turn decreased intestinal epithelial permeability. Moreover, the reduced microbial diversity seen in the gut of mice treated with antibiotics was remarkably improved with the administration of Saireito. In addition, Saireito altered the composition of gut microbiota in these mice. These results suggest that Saireito alleviates leaky gut caused by antibiotic-induced dysbiosis. Our findings provide a potentially new therapeutic strategy for antibiotic-related gastrointestinal disorders.
抗生素会破坏正常的肠道微生物群并导致菌群失调，从而降低肠道上皮屏障功能。肠道上皮屏障的破坏，即所谓的“肠漏”，会导致肠道通透性增加，并有助于炎症性肠病和肠易激综合征等胃肠道疾病的发展或恶化。我们之前报道了一种与氨苄西林和万古霉素给药引起的菌群失调相关的肠道上皮屏障功能障碍的小鼠模型。薬膳，一种传统的日本草药，常用于治疗包括溃疡性结肠炎在内的自身免疫性疾病；然而，其作用机制和疗效尚不清楚。在这项研究中，我们在与菌群失调相关的“肠漏”动物模型中检验了薬膳的疗效。C57BL/6 小鼠在整个实验期间（第 1-28 天）喂食薬膳饮食。为了诱导结肠炎，氨苄西林和万古霉素连续 7 天添加到饮用水中（第 22-28 天）。如前所述，抗生素治疗会导致粪便潜血，盲肠增大伴黑色变色，结肠炎症伴上皮细胞凋亡，以及促炎细胞因子的上调。口服薬膳通过抑制结肠炎症，显著改善了抗生素引起的粪便潜血和盲肠增大。此外，薬膳治疗通过抑制细胞凋亡并诱导包括 ZO-1、occludin 和 E-cadherin 在内的细胞黏附蛋白，确保了肠道上皮屏障的完整性，从而降低了肠道上皮通透性。此外，用抗生素治疗的小鼠肠道中观察到的微生物多样性减少，在用薬膳治疗后得到了显著改善。此外，薬膳改变了这些小鼠肠道微生物群的组成。这些结果表明，薬膳减轻了抗生素诱导的菌群失调引起的“肠漏”。我们的发现为抗生素相关的胃肠道疾病提供了一种潜在的新治疗策略。
