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厌食症小鼠模型中肠道微生物群的改变。

Gut microbiota alteration in a mouse model of Anorexia Nervosa.

机构信息

Normandie Univ, UNIROUEN, INSERM UMR1073, Nutrition, inflammation et dysfonction de l'axe intestin-cerveau, Rouen, France; Normandie Univ, UNIROUEN, Institute for Research and Innovation in Biomedicine (IRIB), Rouen, France; Rouen University Hospital, Nutrition Department, Rouen, France.

Normandie Univ, UNIROUEN, INSERM UMR1073, Nutrition, inflammation et dysfonction de l'axe intestin-cerveau, Rouen, France; Normandie Univ, UNIROUEN, Institute for Research and Innovation in Biomedicine (IRIB), Rouen, France.

出版信息

Clin Nutr. 2021 Jan;40(1):181-189. doi: 10.1016/j.clnu.2020.05.002. Epub 2020 May 11.

DOI:10.1016/j.clnu.2020.05.002
PMID:32460959
Abstract

BACKGROUND & AIMS: Anorexia Nervosa is a severe disease depending on both biological, psychological and environmental factors. The gut microbiota has recently been proposed as one of the biological factors potentially involved in the onset or maintenance of Anorexia Nervosa. To unravel the potential role of the gut microbiota in this disease, we characterized the dysbiosis occurring in a mouse model of Anorexia and correlated bacteria level changes with different physiological parameters such as body weight, food intake or levels of hypothalamic neuropeptides.

METHODS

We used the Activity-Based Anorexia (ABA) mouse model, which combines food restriction and physical activity, and which mimics core features of Anorexia Nervosa. We characterized the gut microbiota alteration in ABA mice by combining 16S rRNA gene sequencing and quantitative PCR analyses of targeted genera or species.

RESULTS

We identified 68 amplicon sequence variants (ASVs) with decreased levels and 8 ASVs with increased levels in the cecal content of ABA mice compared to control mice. We observed in particular in ABA mice increases in the abundance of Clostridium cocleatum and several Lactobacillus species and a decrease in the abundance of Burkholderiales compared to control mice. Interestingly, we show that most of the observed gut microbiota alterations are due to food restriction and are not affected by physical activity. In addition, we identified several bacterial groups that correlate with mice body weight, food intake, lean and fat masses as well as with hypothalamic mRNA levels of NPY (Neuropeptide Y) and POMC (Pro-opiomelanocortin).

CONCLUSIONS

Our study provides a comprehensive characterization of the gut microbiota dysbiosis occurring in the Activity-Based Anorexia mouse model. These data constitute a valuable resource to further decipher the role of the gut microbiota in the different facets of anorexia pathophysiology, such as functional gastrointestinal disorders, appetite regulation and mood disorders.

摘要

背景与目的

神经性厌食症是一种严重的疾病,其发生取决于生物、心理和环境等多种因素。肠道微生物群最近被认为是可能参与神经性厌食症发病或维持的生物因素之一。为了阐明肠道微生物群在这种疾病中的潜在作用,我们对神经性厌食症的一种小鼠模型中的肠道菌群失调进行了特征描述,并将细菌水平的变化与体重、食物摄入量或下丘脑神经肽水平等不同生理参数相关联。

方法

我们使用了活动型厌食症(ABA)小鼠模型,该模型结合了食物限制和体力活动,模拟了神经性厌食症的核心特征。我们通过 16S rRNA 基因测序和靶向属或种的定量 PCR 分析相结合,来描述 ABA 小鼠肠道微生物群的改变。

结果

与对照小鼠相比,我们在 ABA 小鼠的盲肠内容物中鉴定出 68 个丰度降低的扩增子序列变异(ASV)和 8 个丰度增加的 ASV。特别是,我们观察到 ABA 小鼠中梭菌 cocleatum 和几种乳杆菌属的丰度增加,而与对照小鼠相比,伯克霍尔德菌的丰度降低。有趣的是,我们发现大多数观察到的肠道微生物群变化是由于食物限制引起的,而不受体力活动的影响。此外,我们还鉴定出了一些与小鼠体重、食物摄入量、瘦肉和脂肪质量以及下丘脑 NPY(神经肽 Y)和 POMC(促黑激素原)mRNA 水平相关的细菌群。

结论

我们的研究提供了对活动型厌食症小鼠模型中肠道菌群失调的全面描述。这些数据构成了一个有价值的资源,可以进一步阐明肠道微生物群在厌食症病理生理学的不同方面的作用,如功能性胃肠疾病、食欲调节和情绪障碍。

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