Song Zhuan, Si Xuemeng, Zhang Xinyu, Chen Jingqing, Jia Hai, He Yu, Liu Haozhen, Kou Zongyue, Dai Zhaolai, Wu Zhenlong
State Key Laboratory of Animal Nutrition, Department of Companion Animal Science, China Agricultural University, Beijing, P. R. China; Beijing Jingwa Agricultural Science and Technology Innovation Center, Beijing, P. R. China.
State Key Laboratory of Animal Nutrition, Department of Companion Animal Science, China Agricultural University, Beijing, P. R. China.
J Nutr. 2023 Feb;153(2):532-542. doi: 10.1016/j.tjnut.2022.12.004. Epub 2022 Dec 25.
Salmonella typhimurium is a pathogen that causes gastroenteritis in humans and animals. Amuc_1100 (hereafter called Amuc), the outer membrane protein of Akkermansia muciniphila, alleviates metabolic disorders and maintains immune homeostasis.
This study was conducted to determine whether there is a protective effect of Amuc administration.
Male 6-wk-old C57BL6J mice were randomly allocated into 4 groups: CON (control), Amuc (gavaged with Amuc, 100 μg/d for 14 d), ST (oral administration of 1.0 × 10 CFU S. typhimurium on day 7), and ST + Amuc (Amuc supplementation for 14 d, S. typhimurium administration on day 7). Serum and tissue samples were collected 14 d after treatment. Histological damage, inflammatory cell infiltration, apoptosis, and protein levels of genes associated with inflammation and antioxidant stress were analyzed. Data were analyzed by 2-way ANOVA and Duncan's multiple comparisons using SPSS software.
The ST group mice had 17.1% lower body weight, 1.3-3.6-fold greater organ index (organ weight/body weight for organs including the liver and spleen), 10-fold greater liver damage score, and 3.4-10.1-fold enhanced aspartate transaminase, alanine transaminase, and myeloperoxidase activities, and malondialdehyde and hydrogen peroxide concentrations compared with controls (P < 0.05). The S. typhimurium-induced abnormalities were prevented by Amuc supplementation. Furthermore, the ST + Amuc group mice had 1.44-1.89-fold lower mRNA levels of proinflammatory cytokines (interleukin [Il]6, Il1b, and tumor necrosis factor-α) and chemokines (chemokine ligand [Ccl]2, Ccl3, and Ccl8) and 27.1%-68.5% lower levels of inflammation-related proteins in the liver than ST group mice (P < 0.05).
Amuc treatment prevents S. typhimurium-induced liver damage partly through the toll-like receptor (TLR)2/TLR4/myeloid differentiation factor 88 and nuclear factor-κB signaling as well as nuclear factor erythroid-2 related factor signaling pathways. Thus, Amuc supplementation may be effective in treating liver injury in S. typhimurium-challenged mice.
鼠伤寒沙门氏菌是一种可导致人类和动物患肠胃炎的病原体。嗜黏蛋白阿克曼氏菌的外膜蛋白Amuc_1100（以下简称Amuc）可缓解代谢紊乱并维持免疫稳态。
本研究旨在确定给予Amuc是否具有保护作用。
将6周龄雄性C57BL6J小鼠随机分为4组：CON（对照组）、Amuc组（灌胃给予Amuc，100μg/d，共14天）、ST组（第7天口服1.0×10⁸CFU鼠伤寒沙门氏菌）和ST + Amuc组（补充Amuc 14天，第7天给予鼠伤寒沙门氏菌）。治疗14天后收集血清和组织样本。分析组织学损伤、炎性细胞浸润、细胞凋亡以及与炎症和抗氧化应激相关基因的蛋白水平。使用SPSS软件通过双向方差分析和邓肯多重比较对数据进行分析。
与对照组相比，ST组小鼠体重降低17.1%，器官指数（包括肝脏和脾脏等器官的器官重量/体重）高1.3 - 3.6倍，肝脏损伤评分高10倍，天冬氨酸转氨酶、丙氨酸转氨酶和髓过氧化物酶活性以及丙二醛和过氧化氢浓度提高3.4 - 10.1倍（P < 0.05）。补充Amuc可预防鼠伤寒沙门氏菌诱导的异常情况。此外，与ST组小鼠相比，ST + Amuc组小鼠肝脏中促炎细胞因子（白细胞介素[Il]6、Il1b和肿瘤坏死因子-α）和趋化因子（趋化因子配体[Ccl]2、Ccl3和Ccl8）的mRNA水平低1.44 - 1.89倍，炎症相关蛋白水平低27.1% - 68.5%（P < 0.05）。
Amuc治疗可部分通过Toll样受体（TLR）2/TLR4/髓样分化因子88和核因子-κB信号通路以及核因子红细胞2相关因子信号通路预防鼠伤寒沙门氏菌诱导的肝脏损伤。因此，补充Amuc可能对治疗鼠伤寒沙门氏菌攻击的小鼠的肝损伤有效。
