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特应性皮炎小鼠肠道菌群及代谢产物的变化

The changes of intestinal flora and metabolites in atopic dermatitis mice.

作者信息

Wang Feifei, Wang Zuding, Qu Liping

机构信息

Yunnan Botanee Bio-Technology Group Co., Ltd., Kunming, China.

Yunnan Characteristic Plant Extraction Laboratory, Yunnan Yunke Characteristic Plant Extraction Laboratory Co., Ltd., Kunming, China.

出版信息

Front Microbiol. 2024 Dec 16;15:1462491. doi: 10.3389/fmicb.2024.1462491. eCollection 2024.

DOI:10.3389/fmicb.2024.1462491
PMID:39736988
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11683101/
Abstract

INTRODUCTION

Atopic dermatitis (AD) is an allergic disease caused by various factors that can affect an individual's appearance and cause psychological stress. Therefore, it is necessary to investigate the underlying mechanisms and develop effective treatment strategies. The gut microbiota and bacterial metabolism play crucial roles in human diseases. However, their specific role in AD remains unclear.

METHODS

In this study, we established a mouse model of AD and found that 2,4-dinitrofluorobenzene disrupted the skin barrier in mice. The species composition of intestinal bacteria was then analyzed by fecal 16s rRNA sequencing. The metabolic level of mice was analyzed by untargeted and targeted metabolomics in stool.

RESULTS

The levels of filaggrin and aquaporin 3 proteins in the model mice and total superoxide dismutase, catalase and malondialdehyde levels were significantly altered. Additionally, inflammatory factors such as tumor necrosis factor-alpha showed a significant increase. Using 16S rRNA gene sequencing, we identified 270 bacterial species with altered abundances of and . The untargeted metabolomic analysis detected 1,299 metabolites. Targeted analysis of free fatty acids revealed 49 metabolites with notable increases in linoleic and linolenic acid levels. Fecal bacterial transplantation experiments have demonstrated that oxidative stress, inflammation, and skin barrier damage were alleviated after transplantation.

DISCUSSION

These findings suggested that the metabolite linoleic acid negatively correlated with and may influence AD development. Perturbations in the intestinal bacteria and flora contributed to the development of AD, and the mouse model could serve as a valuable tool for further investigation of therapeutic approaches for managing ADS.

摘要

引言

特应性皮炎(AD)是一种由多种因素引起的过敏性疾病,会影响个人外貌并导致心理压力。因此,有必要研究其潜在机制并制定有效的治疗策略。肠道微生物群和细菌代谢在人类疾病中起着关键作用。然而,它们在AD中的具体作用仍不清楚。

方法

在本研究中,我们建立了AD小鼠模型,发现2,4-二硝基氟苯破坏了小鼠的皮肤屏障。然后通过粪便16s rRNA测序分析肠道细菌的物种组成。通过对粪便进行非靶向和靶向代谢组学分析小鼠的代谢水平。

结果

模型小鼠中丝聚合蛋白和水通道蛋白3的水平以及总超氧化物歧化酶、过氧化氢酶和丙二醛的水平均发生了显著变化。此外,肿瘤坏死因子-α等炎症因子显著增加。使用16S rRNA基因测序,我们鉴定出270种丰度发生变化的细菌物种。非靶向代谢组学分析检测到1299种代谢物。对游离脂肪酸的靶向分析显示,亚油酸和亚麻酸水平显著增加的有49种代谢物。粪便细菌移植实验表明,移植后氧化应激、炎症和皮肤屏障损伤得到缓解。

讨论

这些发现表明,与丰度呈负相关的代谢物亚油酸可能影响AD的发展。肠道细菌和菌群的紊乱促成了AD的发展,该小鼠模型可作为进一步研究AD治疗方法的有价值工具。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ff75/11683101/688e1b38f44d/fmicb-15-1462491-g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ff75/11683101/5b3fe9f61137/fmicb-15-1462491-g001.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ff75/11683101/0f2625da34f5/fmicb-15-1462491-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ff75/11683101/4fb3c7f76e67/fmicb-15-1462491-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ff75/11683101/d907c4ce0fd2/fmicb-15-1462491-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ff75/11683101/a453a19b4457/fmicb-15-1462491-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ff75/11683101/688e1b38f44d/fmicb-15-1462491-g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ff75/11683101/5b3fe9f61137/fmicb-15-1462491-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ff75/11683101/127eb16e4abe/fmicb-15-1462491-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ff75/11683101/b86471e3823e/fmicb-15-1462491-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ff75/11683101/0f2625da34f5/fmicb-15-1462491-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ff75/11683101/4fb3c7f76e67/fmicb-15-1462491-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ff75/11683101/d907c4ce0fd2/fmicb-15-1462491-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ff75/11683101/a453a19b4457/fmicb-15-1462491-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ff75/11683101/688e1b38f44d/fmicb-15-1462491-g008.jpg

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本文引用的文献

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GDU-952, a novel AhR agonist ameliorates skin barrier abnormalities and immune dysfunction in DNFB-induced atopic dermatitis in mice.GDU-952,一种新型 AhR 激动剂,可改善 DNFB 诱导的小鼠特应性皮炎的皮肤屏障异常和免疫功能障碍。
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Bacterial Metabolites: A Link between Gut Microbiota and Dermatological Diseases.细菌代谢产物:肠道微生物群与皮肤疾病之间的联系。
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