Cheng Yu-Hsuan, Li Hung-Keng, Chang Kai-Hsian, Lin Yung-Kai, Lin Yung-Hsiang, Chiang Chi-Fu, Yang Jyh-Chin, Chien Chiang-Ting
Department of Life Science, School of Life Science, National Taiwan Normal University, Taipei, Taiwan, ROC.
Division of Urology, Department of Surgery, Far-Eastern Memorial Hospital, New Taipei City, Taiwan, ROC.
J Chin Med Assoc. 2025 Jul 1;88(7):545-560. doi: 10.1097/JCMA.0000000000001246. Epub 2025 May 9.
Probiotic Bacillus coagulans (BC) may have an impact on gastrointestinal protection. This study was designed to investigate the BC effects on Helicobacter pylori ( H. pylori ) induced gastric inflammation in mice and acid-induced lower esophageal sphincter (LES) dysfunction in rats. We determined the oxidative stress/apoptosis/autophagy signaling pathways in H. pylori -induced gastric inflammation and HCl-evoked LES inflammation.
H. pylori -induced gastric inflammation was used in 40 mice and HCl-evoked LES inflammation in 40 Wistar rats. Western blot, immunohistochemistry and cytokine array were used to determine the pathophysiologic mechanisms.
H. pylori increased leukocyte infiltration-mediated inflammation and the expression levels of gastric cytokines, 3NT/4HNE-mediated oxidative stress, and Bax/Caspase3-mediated apoptosis, but decreased Beclin-1/LC3-II-mediated autophagy in the mice gastric mucosa. BC treatment decreased inflammation, cytokines release, oxidative stress, and apoptosis, and reversed autophagy in H. pylori -infected gastric mucosa. To replace the antibiotic therapy, BC TCI803 was selected to inhibit H. pylori infection for commercial interests. Saline esophageal infusion evoked an increase in LES pressure and efferent vagus nerve activity during the emptying phase. However, HCI dysregulated LES motility esophageal infusion by a decrease in threshold pressure, intercontraction interval and an increase in efferent vagus nerve activity. BC treatment significantly recovered the level of threshold pressure, intercontraction interval, and depressed the enhanced efferent vagus nerve activity. In vitro LES wire myography data displayed that HCl-treated LES significantly decreased the contractile response to acetylcholine. BC treatment significantly restored the contractile response to acetylcholine in LES wire myography. LES after HCl stimulation significantly increased leukocyte infiltration-mediated inflammation, whereas BC treatment effectively reduced the leukocyte infiltration-mediated inflammation in the HCl-treated LES.
BC via anti-oxidation and anti-inflammation confers gastroesophageal protection against H. pylori involved oxidative stress/inflammation/apoptosis/autophagy signaling in mice with gastric inflammation and HCl-induced LES dysregulation and inflammation.
益生菌凝结芽孢杆菌（BC）可能对胃肠道有保护作用。本研究旨在探讨BC对幽门螺杆菌（H. pylori）诱导的小鼠胃炎症以及酸诱导的大鼠食管下括约肌（LES）功能障碍的影响。我们确定了幽门螺杆菌诱导的胃炎症和盐酸诱发的LES炎症中的氧化应激/凋亡/自噬信号通路。
40只小鼠用于幽门螺杆菌诱导的胃炎症研究，40只Wistar大鼠用于盐酸诱发的LES炎症研究。采用蛋白质免疫印迹法、免疫组织化学法和细胞因子阵列法来确定病理生理机制。
幽门螺杆菌增加了白细胞浸润介导的炎症以及胃细胞因子的表达水平、3NT/4HNE介导的氧化应激和Bax/Caspase3介导的凋亡，但降低了小鼠胃黏膜中Beclin-1/LC3-II介导的自噬。BC治疗可减轻炎症、细胞因子释放、氧化应激和凋亡，并逆转幽门螺杆菌感染胃黏膜中的自噬。出于商业利益考虑，选择BC TCI803来抑制幽门螺杆菌感染以替代抗生素治疗。生理盐水食管灌注在排空期引起LES压力和传出迷走神经活动增加。然而，盐酸通过降低阈值压力、收缩间期并增加传出迷走神经活动来失调LES运动性食管灌注。BC治疗显著恢复了阈值压力、收缩间期水平，并抑制了增强的传出迷走神经活动。体外LES线肌动描记术数据显示，盐酸处理的LES显著降低了对乙酰胆碱的收缩反应。BC治疗显著恢复了LES线肌动描记术中对乙酰胆碱的收缩反应。盐酸刺激后的LES显著增加了白细胞浸润介导的炎症，而BC治疗有效减轻了盐酸处理的LES中白细胞浸润介导的炎症。
BC通过抗氧化和抗炎作用，对幽门螺杆菌参与的氧化应激/炎症/凋亡/自噬信号通路导致的胃炎症小鼠以及盐酸诱导的LES失调和炎症起到胃食管保护作用。
