Department of Microbiology, Institute for Immunology and Immunological Disease, Graduate School of Medical Science, Brain Korea 21 Project, Yonsei University College of Medicine, Seoul, South Korea.
Nodcure, Inc., 77 Yongbong-ro, Buk-gu, Gwangju 61186, South Korea.
Int Immunopharmacol. 2024 May 10;132:111937. doi: 10.1016/j.intimp.2024.111937. Epub 2024 Apr 2.
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.
结核病（TB）的治疗需要长期的治疗过程，并会产生肝毒性等不良反应，导致治疗中断。TB 药物治疗的依从性降低会增加复发和产生耐药性的风险。此外，具有高结核分枝杆菌（Mtb）负荷和炎症介导的组织损伤的严重空洞性 TB 可能需要延长治疗时间，从而导致更高的药物诱导毒性倾向。我们之前报道过，植物乳杆菌 CVL-001（L. sakei CVL-001）的给药可调节炎症并改善小鼠结肠炎模型中的粘膜屏障功能。由于越来越多的证据报告了益生菌在药物性肝损伤和肺部炎症中的功能作用，我们采用共生形式的 L. sakei CVL-001 来研究这种补充剂是否可能对化疗期间减少药物诱导的肝损伤和肺部炎症有益。有趣的是，L. sakei CVL-001 的给药略微降低了 Mtb 负担，而在 Mtb 耐药和敏感的小鼠中均不影响肺部炎症和体重减轻。此外，L. sakei CVL-001 降低了 T 细胞介导的炎症反应，增加了调节性 T 细胞，并提高了抗原特异性 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，共生干预显著降低了丙氨酸氨基转移酶（肝毒性的一个指标）的水平，并降低了肝组织中的细胞死亡。总的来说，我们的数据表明，L. sakei CVL-001 的给药具有作为辅助治疗的潜力，可减少抗 TB 药物治疗期间的肺部炎症和肝损伤，并可能有益于 TB 药物治疗的长期依从性。
