The effect of Akkermansia muciniphila on ileal apoptosis and autophagy signaling pathway related gene expression in mice stimulated by Escherichia coli K88

doi:10.14088/j.cnki.issn0439-8114.2025.06.023

Abstract

Abstract: To investigate the effect of Akkermansia muciniphila (AKK) on the expression of genes related to apoptosis and autophagy signaling pathways in the ileum after toxinogenic Escherichia coli (ETEC) K88 stimulation induces intestinal injury, 18 female BALB/c mice (5~6 weeks old, weighing 18±1 g) were randomly divided into 3 treatment groups, each treatment with 6 replicates. After 1 week of normal feeding, the mice were orally gavaged with PBS, live AKK bacteria, or heat-inactivated AKK bacteria. The gavage was performed once every 2 d, and after 2 weeks of continuous gavage, ETEC K88 bacterial solution was intraperitoneally injected for infection, and after 36 h, the mice were anesthetized and sacrificed, and intestinal samples were retrieved to detect the expression of genes related to apoptosis and autophagy signaling pathway. The results showed as follows: (1) AKK bacteria and inactivated AKK bacteria had alleviating effects on the damage of ileal morphology and structure caused by ETEC K88 infection. (2) Both gavage and inactivated AKK significantly down-regulated the mRNA expression of interleukin IL-1β, IL-6 and tumor necrosis factor-α (TNF-α) in the ileum of mice (P<0.05). (3) AKK significantly reduced the mRNA expression levels of Fasl, Caspase 3, Caspase 9 and Bcl-2-related X protein (Bax), which are related to the apoptosis signaling pathway in mice, (P<0.05). (4) AKK bacteria or inactivated AKK bacteria significantly reduced the mRNA expression levels of mammalian lepatoxin target protein (mTOR), and autophagy-related gene 12 (Atg12) in the ileum of mice (P<0.05). AKK bacteria has a certain alleviating effect on ileal injury in mice caused by ETEC K88 infection.

Key words: toxinogenic, Escherichia coli K88, Akkermansia muciniphila, ileum, apoptosis, autophagy

CLC Number:

S852.61

ZHANG Zi-han, LIU Li-xue, HU Jin. The effect of Akkermansia muciniphila on ileal apoptosis and autophagy signaling pathway related gene expression in mice stimulated by Escherichia coli K88[J]. HUBEI AGRICULTURAL SCIENCES, 2025, 64(6): 141-145.

References

[1] FAIRBROTHER J M, NADEAU É, GYLES C L.Escherichia coli in postweaning diarrhea in pigs: an update on bacterial types, pathogenesis, and prevention strategies[J]. Animal health research reviews, 2005;6(1):17-39.
[2] ZHANG W, ZHAO M, RUESCH L, et al.Prevalence of virulence genes in Escherichia coli strains recently isolated from young pigs with diarrhea in the US[J]. Veterinary microbiology, 2007,123(1-3):145-152.
[3] 孙奇娟,张昊恺,刘佳隆,等. 产肠毒素大肠杆菌黏附素基因多重PCR检测方法的建立与应用[J]. 中国兽医科学,2022,52(8):970-977.
[4] MA N, WEI G, ZHANG H, et al.Cis-9, Trans-11 CLA alleviates lipopolysaccharide-Induced depression of fatty acid synthesis by inhibiting oxidative stress and autophagy in bovine mammary epithelial cells[J]. Antioxidants. 2022,11(1):55.
[5] 张萱,杨雪,李新科,等. 丁酸钠对幼鼠回肠发育、炎症因子及物理屏障功能的调控作用[J]. 畜牧兽医学报,2025,56(3):1278-1289.
[6] 冯丹,张民扬,田时祎,等. 日粮添加壳聚糖螯合锌对大肠杆菌攻毒断奶大鼠回肠形态结构及屏障功能的影响[J]. 南京农业大学学报,2021,44(3):541-547.
[7] 侯国珺. 壳聚糖螯合锌对大肠杆菌K88攻毒断奶仔猪回肠和盲肠菌群结构、炎症反应和屏障功能的影响[D]. 南京:南京农业大学,2021.
[8] 张赛群,朱红梅,周涵韬,等. 产肠毒素性大肠杆菌K88的致病特性及其益生菌的筛选[J]. 中国兽医科学,2008,38(5):386-392.
[9] DERRIEN M, ELAZNE V, CAROLINE M P, et al.Akkermansia muciniphila gen. nov., sp. nov., a human intestinal mucin-degrading bacterium[J]. International journal of systematic and evolutionary microbiology, 2004,54(5):1469-1476.
[10] SHIN H Y, HWAN C C, SIK M Y, et al.Akkermansia muciniphila secretes a glucagon-like peptide-1-inducing protein that improves glucose homeostasis and ameliorates metabolic disease in mice[J]. Nature microbiology, 2021,6(5):563-573.
[11] 王祥煌,杜雯鹃,徐乐,等. 嗜黏蛋白阿克曼菌的生理功能及其在动物生产中的应用前景[J]. 动物营养学报,2023,35(9):5598-5610.
[12] FANG J, ZHANG H, ZHANG X, et al.Akkermansia muciniphila improves gastric cancer treatment by modulating the immune microenvironment[J]. Future microbiol, 2024,19(6):481-494.
[13] LI Y, HUANG H, XIE H, et al.Akkermansia muciniphila activates natural killer cells by suppressing the TGF-β signaling pathway in lung adenocarcinoma cells[J]. Cytokine, 2025,186:156833.
[14] WOONG T W, SIK H K, NARI S, et al.Calf Diarrhea caused by prolonged expansion of autochthonous gut Enterobacteriaceae and their lytic bacteriophages[J]. mSystems, 2021,6(2): e00816-20.
[15] MARC S, AMANDINE E, G A G, et al. Akkermansia muciniphila inversely correlates with the onset of inflammation, altered adipose tissue metabolism and metabolic disorders during obesity in mice[J]. Scientific reports, 2015,5(1):16643.
[16] 李敏,林俊. 细胞凋亡途径及其机制[J]. 国际妇产科学杂志,2014,41(2):103-107.
[17] 秦旭,周墨涵,尉心田,等. 脂多糖刺激后不同时间点断奶仔猪肠道中凋亡和自噬信号通路的动态变化[J]. 动物营养学报,2023,35(3):1513-1519.
[18] YOSHINORI O.Historical landmarks of autophagy research[J]. Cell research, 2014,24(1):9-23.
[19] 韩姣,曾凡军,陈世雄,等. 细胞自噬与凋亡关系的分子机制研究进展[J]. 海南医学,2016,27(4):604-606.
[20] 杨阳,黄兴法,王东方,等. 产肠毒素大肠杆菌K88诱导BALB/c小鼠空肠损伤的机制研究[J]. 中国畜牧杂志,2021,57(11):213-216.
[21] 陈逢. 鱼油通过TLR4和NOD信号通路对脂多糖诱导的仔猪肠道、肝脏损伤和肌肉蛋白质降解的调控作用[D]. 武汉:武汉轻工大学,2013.
[22] 郭俊杰. 细胞程序性坏死在脂多糖诱导的仔猪肌肉蛋白质降解中的作用[D].武汉: 武汉轻工大学,2022.
[23] LIVAK K J, SCHMITTGEN T D.Analysis of relative gene expression data using real-time quantitative PCR and 2-ΔΔCt method[J]. Methods, 2001,25(4):402-408.
[24] WU T, ZHANG Y, LV Y, et al.Beneficial impact and molecular mechanism of Bacillus coagulans on piglets' intestine[J]. International journal of molecular sciences, 2018,19(7):2084.
[25] CAMPBELL M J, CRENSHAW D J, POLO J.The biological stress of early weaned piglets[J]. Journal of animal science and biotechnology, 2013,4(1):19.
[26] GAO Y H, HAN F, HUANG X H, et al.Changes in gut microbial populations, intestinal morphology, expression of tight junction proteins, and cytokine production between two pig breeds after challenge with Escherichia coli K88: A comparative study[J]. Journal of animal science, 2013,91(12):5614-5625.
[27] YU E, CHEN D W, YU B, et al.Manno-oligosaccharide attenuates inflammation and intestinal epithelium injury in weaned pigs upon Enterotoxigenic Escherichia coli K88 challenge[J]. The British journal of nutrition, 2020,126(7):31-37.
[28] 赵佳琳,董卫国. Akk菌在消化道疾病中的研究进展[J]. 中国现代医学杂志,2023,33(2):43-47.
[29] ZHANG H, PAN Y, JIANG Y, et al.Akkermansia muciniphila ONE effectively ameliorates dextran sulfate sodium (DSS)-induced ulcerative colitis in mice[J]. NPJ Sci food, 2024, 8:97.