Fucose Ameliorate Intestinal Inflammation Through Modulating the Crosstalk Between Bile Acids and Gut Microbiota in a Chronic Colitis Murine Model
Fucose Ameliorate Intestinal Inflammation Through Modulating the Crosstalk Between Bile Acids and Gut Microbiota in a Chronic Colitis Murine Model
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岩藻糖通过调节慢性结肠炎小鼠模型中胆汁酸和肠道微生物群之间的串扰来改善肠道炎症
DOI：
10.1093/ibd/izaa007
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发表时间：
2020-06-01
影响因子：
4.9
通讯作者：
Hou, Xiaohua
中科院分区：
文献类型：
--
作者：
Ke, Jun;Li, Ying;Hou, Xiaohua
背景：复发性肠道炎症通常与异常胆汁酸谱和微生物群落有关。在肠道病原菌感染的情况下，病灶对共生菌有保护作用。我们推测，在慢性结肠炎的情况下，病灶也可能对微生物生态系统有一定的影响。方法：为了验证我们的假设，在存在或不存在病灶的慢性葡聚糖硫酸钠（DSS）小鼠模型中进行多组学检查，结合微生物组学和代谢组学。采用16S RNA测序测定回肠和结肠菌群。采用超高效液相色谱-质谱联用（UPLC-MS）对一级和二级胆汁酸及其相应的牛磺酸和甘氨酸偶联物进行定量分析。此外，还检测到参与调节胆汁酸合成的酶。最后，对抗生素治疗的小鼠进行了一项实验，以检查肠道微生物群的作用。结果：无外源性病灶可明显减轻结肠炎小鼠的炎症反应。此外，在病灶存在的情况下，DSS小鼠体内积累过多的肠道胆汁酸减少，同时肝脏胆汁酸合成的受损调节也得以恢复。此外，胆汁酸谱的变化与肠道微生物群失调的改善有关。然而，在抗生素鸡尾酒治疗的小鼠中，病灶的保护作用被消除，这表明微生物群发挥了关键作用。结论：本研究结果表明，聚焦通过恢复胆汁酸和肠道微生物群之间的相互作用来改善结肠炎。
Background: Recurrent intestinal inflammation is frequently associated with aberrant bile acid profiles and microbial community. Fucose exerts a protective effect on commensal bacteria in the case of intestinal pathogen infection. We speculated that fucose might also have certain impact on the microbial ecosystem under the chronic colitis setting.Methods: To validate our hypothesis, multi-omics examination was performed in combination with microbiomics and metabonomics in a chronic dextran sulfate sodium (DSS) murine model in the presence or absence of fucose. The 16S RNA sequencing was carried out to determine the ileum and colon microbiota. Primary and secondary bile acids, together with the respective taurine and glycine conjugates, were quantified through ultraperformance liquid chromatography coupled with mass spectrometry (UPLC-MS). Moreover, enzymes involved in regulating bile acid synthesis were also detected. Finally, an experiment was carried out on the antibiotic-treated mice to examine the role of gut microbiota.Results: Administration of exogenous-free fucose markedly alleviated the inflammatory response in colitis mice. In addition, excessive intestinal bile acid accumulated in DSS mice was decreased in the presence of fucose, along with the restoration of the compromised regulation on hepatic bile acid synthesis. Moreover, the shifts in bile acid profiles were linked with the improved gut microbiome dysbiosis. However, the protective effects of fucose were abolished in mice treated with antibiotic cocktail, indicating that microbiota played a pivotal role.Conclusions: Findings in this study suggest that fucose ameliorates colitis through restoring the crosstalk between bile acid and gut microbiota.