Key Laboratory of Animal Nutrition and Feed Science, Ministry of Agriculture and Rural Affairs, College of Animal Sciences, Zhejiang University, Hangzhou, China.
Hainan Institute of Zhejiang University, Sanya, China.
Front Immunol. 2023 Jan 12;13:1061627. doi: 10.3389/fimmu.2022.1061627. eCollection 2022.
() is a common food-borne bacterial pathogen that can use the host's innate immune response to induce the development of colitis. There has been some research on the role of normal intestinal flora in -induced colitis, but the mechanisms that play a central role in resistance to infection have not been explored.
We treated Campylobacter jejuni-infected mice with fecal microbiota transplantation (FMT), oral butyric acid and deoxycholic acid in a controlled trial and analyzed the possible mechanisms of treatment by a combination of chromatography, immunohistochemistry, fluorescence in situ hybridization, 16s rRNA gene, proteomics and western blot techniques.
We first investigated the therapeutic effect of FMT on infection. The results showed that FMT significantly reduced the inflammatory response and blocked the invasion of into the colonic tissue. We observed a significant increase in the abundance of Akkermansia in the colon of mice after FMT, as well as a significant increase in the levels of butyric acid and deoxycholic acid. We next demonstrated that oral administration of sodium butyrate or deoxycholic acid had a similar therapeutic effect. Further proteomic analysis showed that induced colitis mainly through activation of the PI3K-AKT signaling pathway and MAPK signaling pathway, whereas Akkermansia, the core flora of FMT, and the gut microbial metabolites butyric acid and deoxycholic acid both inhibited these signaling pathways to counteract the infection of and alleviate colitis. Finally, we verified the above idea by in vitro cellular assays. In conclusion, FMT is highly effective in the treatment of colitis caused by , with which Akkermansia and butyric and deoxycholic acids are closely associated.The present study demonstrates that Akkermansia and butyric and deoxycholic acids are effective in the treatment of colitis caused by .
This is the first time that Akkermansia has been found to be effective in fighting pathogens, which provides new ideas and insights into the use of FMT to alleviate colitis caused by and Akkermansia as a treatment for intestinal sexually transmitted diseases caused by various pathogens.
空肠弯曲菌是一种常见的食源性细菌病原体,它可以利用宿主的固有免疫反应诱导结肠炎的发生。已经有一些关于正常肠道菌群在弯曲菌性结肠炎中的作用的研究,但是在抵抗弯曲菌感染中起核心作用的机制尚未被探索。
我们在对照试验中用粪便微生物移植(FMT)、口服丁酸和脱氧胆酸处理空肠弯曲菌感染的小鼠,并结合色谱、免疫组织化学、荧光原位杂交、16s rRNA 基因、蛋白质组学和 Western blot 技术分析治疗的可能机制。
我们首先研究了 FMT 对感染的治疗效果。结果表明,FMT 显著减轻了炎症反应并阻止了弯曲菌侵入结肠组织。我们观察到 FMT 后小鼠结肠中阿克曼氏菌的丰度显著增加,同时丁酸和脱氧胆酸的水平也显著增加。我们接下来证明口服丁酸钠或脱氧胆酸也有类似的治疗效果。进一步的蛋白质组学分析表明,弯曲菌性结肠炎主要通过激活 PI3K-AKT 信号通路和 MAPK 信号通路而引起,而 FMT 的核心菌群阿克曼氏菌和肠道微生物代谢物丁酸和脱氧胆酸均抑制这些信号通路,从而抵抗弯曲菌的感染并缓解结肠炎。最后,我们通过体外细胞实验验证了上述观点。总之,FMT 对弯曲菌引起的结肠炎具有高度疗效,阿克曼氏菌、丁酸和脱氧胆酸密切相关。本研究表明,阿克曼氏菌和丁酸、脱氧胆酸在治疗弯曲菌引起的结肠炎方面是有效的。
这是首次发现阿克曼氏菌在对抗病原体方面有效,这为利用 FMT 缓解弯曲菌引起的结肠炎以及阿克曼氏菌作为治疗各种病原体引起的肠道性传播疾病提供了新的思路和见解。