基于配方的营养治疗对小鼠模型结肠炎的影响。

The Effect of Formula-based Nutritional Treatment on Colitis in a Murine Model.

机构信息

Division of Gastroenterology, Hepatology and Nutrition, Department of Pediatrics, Yonsei University College of Medicine, Severance Fecal Microbiota Transplantation Center, Severance Hospital, Seoul, Korea.

Department of Medicine, Yonsei University College of Medicine, Seoul, Korea.

出版信息

J Korean Med Sci. 2021 Dec 27;36(50):e342. doi: 10.3346/jkms.2021.36.e342.

DOI:10.3346/jkms.2021.36.e342

PMID:34962114

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8728592/

Abstract

BACKGROUND

Exclusive enteral nutrition (EEN) induces remission in pediatric Crohn's disease (CD). The exact mechanism of EEN therapy in CD is unknown, but alteration of the intestinal microflora after EEN is thought to affect mucosal healing. To determine the link between EEN therapy and therapeutic efficacy in CD, we established a murine model of dextran sulfate sodium (DSS)-induced colitis and applied EEN therapy.

METHODS

Eight-week-old C57BL/6 mice were administered DSS for 4 days to induce colitis, and either normal chow (NC) or EEN was administered for the following 4 days. The mice were grouped according to the feeding pattern after DSS administration: DSS/NC and DSS/EEN groups. The clinical course was confirmed via daily observation of the weight and stool. Fecal samples were collected and 16sRNA sequencing was used. The mice were sacrificed to confirm colonic histopathology.

RESULTS

Weight reduction and increase in disease activity were observed as the day progressed for 4 days after DSS administration. There was significant weight recovery and improvement in disease activity in the EEN group compared to that in the NC group. and abundances tended to increase and abundance decreased in the EEN group. In the EEN group, significant changes in the β-diversity of the microbiota were observed. In the analysis of microbiome species, abundances of , , mucin-degrading bacteria, , and , which are beneficial microbiota, were significantly increased in the EEN group compared to those in the NC group. More abundant mucins were confirmed in the colonic histopathology of the EEN group. These microbial and histopathological differences suggested that EEN might improve colitis symptoms in a murine colitis model by promoting mucin recycling and subsequently inducing the healing effect of the gut barrier.

CONCLUSION

EEN showed clinical efficacy in a murine model of colitis. Based on the increase in mucin-degrading bacteria and the pathological increase in mucin production after EEN administration, it can be observed that mucin plays an important role in the therapeutic effect of EEN.

摘要

背景

肠内营养（EEN）可诱导小儿克罗恩病（CD）缓解。EEN 治疗 CD 的确切机制尚不清楚，但 EEN 后肠道微生物群的改变被认为会影响黏膜愈合。为了确定 EEN 治疗与 CD 治疗效果之间的联系，我们建立了葡聚糖硫酸钠（DSS）诱导的结肠炎小鼠模型并应用 EEN 治疗。

方法

8 周龄 C57BL/6 小鼠给予 DSS 4 天诱导结肠炎，随后给予正常饮食（NC）或 EEN 4 天。根据 DSS 给药后的喂养模式将小鼠分组：DSS/NC 组和 DSS/EEN 组。通过每天观察体重和粪便来确认临床病程。收集粪便样本并进行 16sRNA 测序。处死小鼠以确认结肠组织病理学。

结果

DSS 给药后第 4 天，随着天数的增加，体重减轻和疾病活动度增加。与 NC 组相比，EEN 组的体重恢复和疾病活动度改善明显。EEN 组的和丰度增加，丰度降低。EEN 组的微生物多样性β多样性发生显著变化。在微生物物种分析中，与 NC 组相比，EEN 组有益菌群如、、黏液降解菌、、和的丰度明显增加。EEN 组的结肠组织病理学中确认了更多丰富的黏蛋白。这些微生物和组织病理学差异表明，EEN 通过促进黏蛋白循环，进而诱导肠道屏障的愈合作用，可能改善结肠炎模型中的结肠炎症状。