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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的相互作用改善肠道炎症。

Fucose Ameliorate Intestinal Inflammation Through Modulating the Crosstalk Between Bile Acids and Gut Microbiota in a Chronic Colitis Murine Model.

机构信息

Department of Gastroenterology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.

出版信息

Inflamm Bowel Dis. 2020 May 12;26(6):863-873. doi: 10.1093/ibd/izaa007.

Abstract

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.

摘要

背景

肠道炎症的反复发作常与异常的胆汁酸谱和微生物群落有关。岩藻糖在肠道病原体感染时对共生菌有保护作用。我们推测,岩藻糖在慢性结肠炎的情况下,可能对微生物生态系统也有一定的影响。

方法

为了验证我们的假设,在有或没有岩藻糖的情况下,我们在慢性葡聚糖硫酸钠(DSS)小鼠模型中进行了多组学检查,结合微生物组学和代谢组学。通过 16S RNA 测序来确定回肠和结肠的微生物群。通过超高效液相色谱-串联质谱(UPLC-MS)来定量测定初级和次级胆汁酸,以及各自的牛磺酸和甘氨酸缀合物。此外,还检测了调节胆汁酸合成的酶。最后,在抗生素处理的小鼠上进行了一项实验,以研究肠道微生物群的作用。

结果

外源性游离岩藻糖的给药显著缓解了结肠炎小鼠的炎症反应。此外,在岩藻糖存在的情况下,DSS 小鼠中过度积累的肠道胆汁酸减少,同时恢复了受损的肝胆汁酸合成调节。此外,胆汁酸谱的变化与改善的肠道微生物群失调有关。然而,在接受抗生素鸡尾酒治疗的小鼠中,岩藻糖的保护作用被消除,表明微生物群起了关键作用。

结论

本研究的结果表明,岩藻糖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。

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