Key Laboratory of Experimental Animal and Safety Evaluation, Hangzhou Medical College, Hangzhou, China.
Front Cell Infect Microbiol. 2022 Aug 24;12:997368. doi: 10.3389/fcimb.2022.997368. eCollection 2022.
Antibiotic abuse is growing more severe in clinic, and even short-term antibiotic treatment can cause long-term gut dysbiosis, which may promote the development and aggravation of diseases. Cephalosporins as the broad-spectrum antibiotics are widely used for prevention and treatment of community-acquired respiratory tract infection in children. However, their potential consequences in health and disease have not been fully elaborated. In this study, the effects of cefaclor, cefdinir and cefixime on intestinal microbiota and lung injury were investigated in (Spn)-infected mice. The results showed that the proportion of coccus and bacillus in intestinal microbiota were changed after oral administration with cefaclor, cefdinir and cefixime twice for 10 days, respectively. Compared with the Spn-infected group, the proportion of and in intestine were significantly reduced, while and was increased after cephalosporin treatment. Furthermore, 3 cephalosporins could obviously increase the number of total cells, neutrophils and lymphocytes in BALF as well as the serum levels of endotoxin, IL-2, IL-1β, IL-6 and TNF-α. Mechanically, cephalosporins accelerated Spn-induced pulmonary barrier dysfunction mediating the mRNA expressions of endothelial barrier-related proteins (Claudin 5, Occludin, and ZO-1) and inflammation-related proteins (TLR4, p38 and NF-κB). However, all of those consequences could be partly reversed by treatment, which was closely related to the elevated acetate production, indicating the protective effects of probiotic against antibiotic-induced intestinal dysbiosis. Therefore, the present study demonstrated that oral administration with cephalosporins not only disrupted intestinal microecological homeostasis, but also increased the risk of Spn infection, resulting in severer respiratory inflammation and higher bacterial loads in mice.
临床上抗生素滥用现象日趋严重，即使是短期的抗生素治疗也会导致肠道长期失调，从而促进疾病的发生和恶化。头孢菌素作为广谱抗生素，广泛用于儿童社区获得性呼吸道感染的预防和治疗。然而，它们在健康和疾病方面的潜在后果尚未得到充分阐述。在本研究中，研究了头孢克洛、头孢地尼和头孢克肟对（Spn）感染小鼠肠道微生物群和肺损伤的影响。结果表明，口服头孢克洛、头孢地尼和头孢克肟 10 天，每天两次后，肠道微生物群中球菌和杆菌的比例发生变化。与 Spn 感染组相比，头孢菌素治疗后肠道中 和 的比例明显降低，而 和 的比例增加。此外，3 种头孢菌素均可明显增加 BALF 中总细胞、中性粒细胞和淋巴细胞的数量以及血清中内毒素、IL-2、IL-1β、IL-6 和 TNF-α的水平。在机制上，头孢菌素通过加速 Spn 诱导的肺屏障功能障碍，介导内皮屏障相关蛋白（Claudin 5、Occludin 和 ZO-1）和炎症相关蛋白（TLR4、p38 和 NF-κB）的 mRNA 表达，从而增加 Spn 感染小鼠的肺屏障功能障碍。然而，所有这些后果都可以部分被 治疗逆转，这与乙酸盐产生的增加密切相关，表明益生菌对抗生素诱导的肠道菌群失调具有保护作用。因此，本研究表明，口服头孢菌素不仅破坏了肠道微生态平衡，而且增加了 Spn 感染的风险，导致小鼠呼吸炎症加重和细菌负荷增加。
