Xie Ying, Chupina Estrada Andrea, Nelson Becca, Feng Hanping, Pothoulakis Charalabos, Chesnel Laurent, Koon Hon Wai
Vatche and Tamar Manoukian Division of Digestive Diseases, David Geffen School of Medicine at the University of California Los Angeles, Los Angeles, CA, United States.
Department of Gastroenterology, The First Hospital of China Medical University, Shenyang, Liaoning, China.
Front Microbiol. 2023 Jan 10;13:1072534. doi: 10.3389/fmicb.2022.1072534. eCollection 2022.
infection (CDI) causes intestinal injury. Toxin A and toxin B cause intestinal injury by inducing colonic epithelial cell apoptosis. ADS024 is a strain in development as a single-strain live biotherapeutic product (SS-LBP) to prevent the recurrence of CDI following the completion of standard antibiotic treatment. We evaluated the protective effects of the sterile filtrate and ethyl acetate extract of conditioned media from ADS024 and DSM7 (control strain) against mucosal epithelial injury in toxin-treated human colonic tissues and apoptosis in toxin-treated human colonic epithelial cells. Ethyl acetate extracts were generated from conditioned culture media from DSM7 and ADS024. Toxin A and toxin B exposure caused epithelial injury in fresh human colonic explants. The sterile filtrate of ADS024, but not DSM7, prevented toxin B-mediated epithelial injury in fresh human colonic explants. Both sterile filtrate and ethyl acetate extract of ADS024 prevented toxin-mediated apoptosis in human colonic epithelial cells. The anti-apoptotic effects of ADS024 filtrate and ethyl acetate extract were dependent on the inhibition of caspase 3 cleavage. The sterile filtrate, but not ethyl acetate extract, of ADS024 partially degraded toxin B. ADS024 inhibits toxin B-mediated apoptosis in human colonic epithelial cells and colonic explants.
艰难梭菌感染（CDI）会导致肠道损伤。毒素A和毒素B通过诱导结肠上皮细胞凋亡来造成肠道损伤。ADS024是一种正在开发的单一菌株活生物治疗产品（SS-LBP），用于在标准抗生素治疗完成后预防CDI复发。我们评估了ADS024和DSM7（对照菌株）条件培养基的无菌滤液和乙酸乙酯提取物对毒素处理的人结肠组织中黏膜上皮损伤以及毒素处理的人结肠上皮细胞凋亡的保护作用。乙酸乙酯提取物由DSM7和ADS024的条件培养基制备而成。毒素A和毒素B暴露导致新鲜人结肠外植体出现上皮损伤。ADS024的无菌滤液而非DSM7的无菌滤液可预防新鲜人结肠外植体中毒素B介导的上皮损伤。ADS024的无菌滤液和乙酸乙酯提取物均可预防人结肠上皮细胞中毒素介导的凋亡。ADS024滤液和乙酸乙酯提取物的抗凋亡作用依赖于对半胱天冬酶3切割的抑制。ADS024的无菌滤液而非乙酸乙酯提取物可部分降解毒素B。ADS024可抑制毒素B介导的人结肠上皮细胞和结肠外植体凋亡。
