Abstract：
Tuberculosis (TB) treatment requires a long therapeutic duration and induces adverse effects such as hepatotoxicity, causing discontinuation of treatment. Reduced adherence to TB medications elevates the risk of recurrence and the development of drug resistance. Additionally, severe cavitary TB with a high burden of Mycobacterium tuberculosis (Mtb) and inflammation-mediated tissue damage may need an extended treatment duration, resulting in a higher tendency of drug-induced toxicity. We previously reported that the administration of Lactobacillus sakei CVL-001 (L. sakei CVL-001) regulates inflammation and improves mucosal barrier function in a murine colitis model. Since accumulating evidence has reported the functional roles of probiotics in drug-induced liver injury and pulmonary inflammation, we employed a parabiotic form of the L. sakei CVL-001 to investigate whether this supplement may provide beneficial effects on the reduction in drug-induced liver damage and pulmonary inflammation during chemotherapy. Intriguingly, L. sakei CVL-001 administration slightly reduced Mtb burden without affecting lung inflammation and weight loss in both Mtb-resistant and -susceptible mice. Moreover, L. sakei CVL-001 decreased T cell-mediated inflammatory responses and increased regulatory T cells along with an elevated antigen-specific IL-10 production, suggesting that this parabiotic may restrain excessive inflammation during antibiotic treatment. Furthermore, the parabiotic intervention significantly reduced levels of alanine aminotransferase, an indicator of hepatotoxicity, and cell death in liver tissues. Collectively, our data suggest that L. sakei CVL-001 administration has the potential to be an adjunctive therapy by reducing pulmonary inflammation and liver damage during anti-TB drug treatment and may benefit adherence to TB medication in lengthy treatment.
摘要：
结核病（TB）治疗需要较长的治疗时间，并引起不良作用，如肝毒性，导致停止治疗。对结核病药物的依从性降低会增加复发和耐药性发展的风险。此外,具有高结核分枝杆菌（Mtb）负担和炎症介导的组织损伤的严重空洞性结核病可能需要延长治疗时间，导致药物诱导毒性的趋势更高。我们以前曾报道过，沙木乳杆菌CVL-001(L.sakeiCVL-001）在小鼠结肠炎模型中调节炎症并改善粘膜屏障功能。由于越来越多的证据报道了益生菌在药物性肝损伤和肺部炎症中的功能作用，我们使用了一种副生物形式的沙生乳杆菌CVL-001,以研究这种补充剂是否可以对化疗期间药物诱导的肝损伤和肺部炎症的减少产生有益作用.有趣的是，L.sakeiCVL-001的给药略微降低了Mtb负荷，而不影响Mtb抗性和易感小鼠的肺部炎症和体重减轻。此外，L.sakeiCVL-001减少T细胞介导的炎症反应，增加调节性T细胞，同时增加抗原特异性IL-10的产生，这表明这种共生可能会抑制抗生素治疗期间的过度炎症。此外，同非生物干预显著降低丙氨酸转氨酶水平，肝毒性的指标，和肝组织中的细胞死亡。总的来说，我们的数据表明,沙生乳杆菌CVL-001给药有可能通过减少抗结核药物治疗期间的肺部炎症和肝损伤而成为一种辅助治疗,并且在长期治疗中可能有益于对结核药物的坚持.
