Bacillus coagulans BC66 Attenuates Klebsiella pneumoniae-Induced Acute Lung Injury in Rabbits Associated With Modulation of Th17/Treg Immune Balance and Through the Keap1/Nrf2/HO-1 Signalling Pathway.

Authors

Liandong Ma, Shuaishuai Wang, Ziqiang Zhang, Jiakang Li, Jianing Wang, Chaoying Zhang, Zhe Zhang, Dongliu Luo, Lingping Zhao, Xiaoxia Li, Qiongxia Lv, Xiaoguang Chen, Xuemin Zhu, Lan Wei, Yumei Liu

Published in

Probiotics and antimicrobial proteins. Jun 25, 2026. Epub Jun 25, 2026.

Abstract

Previous studies conducted in our laboratory have demonstrated that dietary supplementation with Bacillus coagulans BC66 (BC66) can mitigate intestinal, renal, and hepatic injuries induced by Klebsiella pneumoniae in rabbits. However, the potential of Bacillus coagulans BC66 in protecting against Klebsiella pneumoniae- induced acute lung injury remains unexplored. Therefore, the present study aimed to investigate the protective mechanism of Bacillus coagulans BC66 against acute lung injury induced by Klebsiella pneumoniae in rabbits using histological examination (hematoxylin and eosin staining, HE staining), immunofluorescence, immunohistochemistry and Western blotting. Dietary supplementation with Bacillus coagulans BC66 alleviated acute lung injury in rabbits by reducing inflammatory cell infiltration, alleviating alveolar wall thickening, and minimizing alveolar lumen narrowing. Additionally, BC66 enhanced the pulmonary barrier by upregulating proliferating cell nuclear antigen (PCNA) expression and modulating the levels of tight junction proteins, including Occludin, Claudin-1, and ZO-1. Importantly, BC66 restored T helper 17/regulatory T cell (Th17/Treg) immune balance, which was identified as the central mechanism underlying its protective effects. This immune modulation was associated with reduced production of pro-inflammatory cytokines, including tumor necrosis factor-alpha (TNF-α), interleukin-1 beta (IL-1β), and interleukin-6 (IL-6), and contributed to the improvement of pulmonary barrier integrity. Furthermore, the regulation of Th17/Treg balance was accompanied by downstream attenuation of oxidative stress and ferroptosis, as evidenced by increased activities of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px), decreased malondialdehyde (MDA) levels, and modulation of ferroptosis-related proteins, including solute carrier family 7 member 11 (SLC7A11) and glutathione peroxidase 4 (GPX4), partly through activation of the Keap1/Nrf2/HO-1 pathway.In conclusion, this study demonstrates that Bacillus coagulans BC66 protects against Klebsiella pneumoniae-induced acute lung injury primarily through restoring Th17/Treg immune balance, with subsequent downstream effects on inflammation, epithelial barrier function, oxidative stress, and ferroptosis. Notably, pretreatment with 1 × 10⁶ colony-forming units per gram (CFU/g) was the most effective. These findings provide a theoretical basis for using Bacillus coagulans BC66 as a preventive agent against acute lung injury induced by Klebsiella pneumoniae in rabbits.

PMID:
42348160
Bibliographic data and abstract were imported from PubMed on 25 Jun 2026.

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