基于“心与小肠相表里”探讨阿尔茨海默病小鼠全肠道菌群移植对回肠肠道微环境的影响

熊伟; 胡林; 许青; 李熙; 丁贤; 窦重阳; 陈芳芳; 闫智勇

doi:10.13471/j.cnki.j.sun.yat-sen.univ(med.sci).2023.0109

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基于“心与小肠相表里”探讨阿尔茨海默病小鼠全肠道菌群移植对回肠肠道微环境的影响

基础研究 | 更新时间：2024-02-19

- 基于“心与小肠相表里”探讨阿尔茨海默病小鼠全肠道菌群移植对回肠肠道微环境的影响
- Probing the Impact of Whole Intestinal Microbiota Transplantation from Alzheimer's Disease Model Mice on the Ileal Microenvironment Based on the “Interior-Exterior Relationship Exists Between Heart and Small Intestine”
- 中山大学学报（医学科学版） 2023年44卷第1期页码：63-70
- 作者机构：
  
  西南交通大学生命科学与工程学院，四川成都 610031
- 作者简介：
  
  熊伟，硕士生，研究方向：中药药理学，E-mail： wei_xiong@my.swjtu.edu.cn
- 基金信息：
  
  中央高校基本科研业务费专项(2682020ZT81);四川省中医药管理局中医药科研专项(2021MS099);成都市科技局技术创新研发项目(2021-YF05-02379-SN)
- DOI：10.13471/j.cnki.j.sun.yat-sen.univ(med.sci).2023.0109
  中图分类号： R229
- 纸质出版日期：2023-01-20，
  
  收稿日期：2022-10-14，
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熊伟,胡林,许青等.基于“心与小肠相表里”探讨阿尔茨海默病小鼠全肠道菌群移植对回肠肠道微环境的影响[J].中山大学学报（医学科学版）,2023,44(01):63-70.

XIONG Wei,HU Ling,XU Qing,et al.Probing the Impact of Whole Intestinal Microbiota Transplantation from Alzheimer's Disease Model Mice on the Ileal Microenvironment Based on the “Interior-Exterior Relationship Exists Between Heart and Small Intestine”[J].Journal of Sun Yat-sen University(Medical Sciences),2023,44(01):63-70.
熊伟,胡林,许青等.基于“心与小肠相表里”探讨阿尔茨海默病小鼠全肠道菌群移植对回肠肠道微环境的影响[J].中山大学学报（医学科学版）,2023,44(01):63-70. DOI： 10.13471/j.cnki.j.sun.yat-sen.univ(med.sci).2023.0109.

XIONG Wei,HU Ling,XU Qing,et al.Probing the Impact of Whole Intestinal Microbiota Transplantation from Alzheimer's Disease Model Mice on the Ileal Microenvironment Based on the “Interior-Exterior Relationship Exists Between Heart and Small Intestine”[J].Journal of Sun Yat-sen University(Medical Sciences),2023,44(01):63-70. DOI： 10.13471/j.cnki.j.sun.yat-sen.univ(med.sci).2023.0109.

摘要

目的

在“心与小肠相表里”中医理论指导下，探讨阿尔茨海默病（AD）模型小鼠全肠道菌群移植，是否对正常小鼠回肠肠道微环境的影响更显著。

方法

将14只6月龄无特定病原体的雄性

APP/PS1

双转基因AD模型小鼠的全肠道菌群，移植至6只混合抗生素处理过的同月龄同背景正常C57BL/6J小鼠肠道内，移植14 d后再定殖14 d，观察小鼠回肠和结肠组织病理变化，并采用16S核糖体RNA（16S rRNA）基因测序技术分析小鼠回肠和结肠菌群。

结果

AD小鼠全肠道菌群移植到正常小鼠后，病理分析表明仅回肠组织出现粘膜层破坏和隐窝腺上皮细胞变性、坏死脱落；测序分析发现，仅回肠菌群的种类数量（

0.01）、Chao1指数（

0.01）和Simpson指数（

0.01）降低且菌群组成和AD模型小鼠更相似。

结论

AD模型小鼠全肠道菌群移植对正常小鼠回肠菌群多样性及组成的影响显著高于结肠菌群，同时导致回肠粘膜的病理损伤，表明回肠肠道微环境可能和AD的发生发展关系更加密切，与“心与小肠相表里”中医理论高度切合。

Abstract

Objective

To investigate whether the whole intestinal microbiota transplantation in Alzheimer's disease （AD） model mice has more significant effects on ileum intestinal microenvironment in normal mice under the guidance of the theory of traditional Chinese medicine that "interior-exterior relationship exists between the heart and small intestine".

Methods

The whole intestinal microbiota of fourteen 6-month-old specific pathogen free male

APP

PS1

double-transgenic AD model mice was transplanted into the gut of six normal C57BL/6J mice of the same age and background treated with mixed antibiotics for 14 days. Then， after 14 days of normal rearing， the mice were sacrificed. Next， the pathological changes in the ileum and colon were observed， and the composition and diversity of the ileal and colonic microbiota was analyzed by sequencing.

Results

After the whole intestinal microbiota of AD mice was transplanted into normal mice， pathological analysis showed that only the ileum tissue had mucosal damage and crypt gland epithelial cell degeneration， necrosis， and shedding. Moreover， the microbiota analysis found that only the number of genera （

0.01）， Chao1 index （

0.01） and Simpson index of ileal microbiota in normal mice decreased （

0.01）， and the composition of intestinal microbiota was quite similar to that of AD model mice.

Conclusion

Under the effect of whole gut microbiota transplantation in AD mice， the diversity and composition of ileal microbiota change more than that of colonic microbiota in normal mice， and at the same time， it results in pathological damage to the ileal mucosa， indicating that the ileal microenvironment may be more closely related to the occurrence and development of AD， which is highly consistent with the traditional Chinese medicine theory of "interior-exterior relationship between heart and small intestine".

关键词

中医理论阿尔茨海默病全肠道菌群移植回肠肠道微环境结肠肠道微环境

Keywords

traditional Chinese medicine theoryAlzheimer's diseasewhole intestinal microbiota transplantationileal microenvironmentcolonic microenvironment

references

鲍婷婷，杨凯麟，龙治勇，等. 基于“心与小肠相表里”探讨肠道菌群与抑郁症［J］. 中国中西医结合杂志，2021，41（4）：499-504.

Bao TT， Yang KL， Long ZY， et al. Discussion on depression and gut microbiota based on the theory of "Xin connecting with small intestine"［J］. Chin J of Integr Tradit West Med， 2021， 41（4）： 499-504.

Yu TW， Lane HY， Lin CH. Novel therapeutic approaches for Alzheimer's disease： an updated review［J］. Int J Mol Sci， 2021， 22（15）：8208.

Kesika P， Suganthy N， Sivamaruthi BS， et al. Role of gut-brain axis， gut microbial composition， and probiotic intervention in Alzheimer's disease［J］. Life Sci， 2021， 264：118627.

刘天浩，张晨阳，韩思思，等. 基于肠道微环境探讨“从肠治肺”的新内涵［J］. 中华中医药杂志，2018，33（12）：5350-5352.

Liu TH，Zhang CY， Han SS， et al. Discussion on new connotation of treating "lung from large intestine" based on intestinal microenvironment［J］. Chin J Tradit Chin Med Pharm， 2018， 33（12）： 5350-5352.

Xu HM， Huang HL， Zhou YL， et al. Fecal microbiota transplantation： a new therapeutic attempt from the gut to the brain［J］. Gastroent Res Pract， 2021， 2021：6699268.

Li N， Zuo B， Huang SM， et al. Spatial heterogeneity of bacterial colonization across different gut segments following inter-species microbiota transplantation［J］. Microbiome， 2020， 8（1）：161.

Khoruts A， Sadowsky MJ. Understanding the mechanisms of faecal microbiota transplantation［J］. Nat Rev Gastro Hepat， 2016， 13（9）：508-516.

Donaldson GP， Lee SM， Mazmanian SK. Gut biogeography of the bacterial microbiota［J］. Nat Rev Microbiol， 2016， 14（1）：20-32.

Martinez-Guryn K， Leone V， Chang EB. Regional diversity of the gastrointestinal microbiome［J］. Cell Host Microbe， 2019， 26（3）：314-324.

Seekatz AM， Schnizlein MK， Koenigsknecht MJ， et al. Spatial and temporal analysis of the stomach and small-intestinal microbiota in fasted healthy humans［J］. Msphere， 2019， 4（2）：e00126-19.

Xu Q， Wen LM， Wei GH， et al. Marked response of rat ileal and colonic microbiota after the establishment of Alzheimer's disease model with bilateral intraventricular injection of Aβ（1-42）［J］. Front Microbiol， 2022， 13：819523.

许青，赵晓芹，刘彦君，等. 基于“心与小肠相表里”探讨回肠菌群在七圣丸抗阿尔茨海默病中的变化［J］. 中国实验方剂学杂志，2022，28（4）：9-18.

Xu Q， Zhao XQ， Liu YJ， et al. Changes in ileal flora induced by Qishengwan in treatment of Alzheimer's disease：an exploration based on "interior-exterior relationship between heart and small intestine"［J］. 2022， 28（4）：9-18.

Wang M， Cao J， Gong C， et al. Exploring the microbiota-Alzheimer's disease linkage using short-term antibiotic treatment followed by fecal microbiota transplantation［J］. Brain Behav Immun， 2021， 96：227-238.

Rogers GB， Keating DJ， Young RL， et al. From gut dysbiosis to altered brain function and mental illness： mechanisms and pathways［J］. Mol Psychiatry， 2016， 21（6）：738-748.

Carabotti M， Scirocco A， Maselli MA， et al. The gut-brain axis： interactions between enteric microbiota， central and enteric nervous systems［J］. Ann Gastroenterol， 2015， 28（2）：203-209.

Sampson TR， Mazmanian SK. Control of brain development， function， and behavior by the microbiome［J］. Cell Host Microbe， 2015， 17（5）：565-576.

李洁，鲁兴启，杨莹，等. 肠易激综合征伴抑郁患者静息态fMRI度中心度的研究［J］. 影像诊断与介入放射学， 2020， 29（2）： 102-106.

Li J， Lu XQ， Yang Y， et al. Degree centrality analysis on resting-state functional MRI in patients with irritable bowel syndrome and depressive symptoms［J］. Diagn Imaging & Interv Radiol， 2020， 29（2）： 102-106.

Yarandi SS， Peterson DA， Treisman GJ， et al. Modulatory effects of gut microbiota on the central nervous system： how gut could play a role in neuropsychiatric health and diseases［J］. J Neurogastroenterol Motil， 2016， 22（2）：201-212.

Gareau MG. Microbiota-gut-brain axis and cognitive function［J］. Adv Exp Med Biol， 2014， 817：357-371.

Kõljalg U， Nilsson RH， Abarenkov K， et al. Towards a unified paradigm for sequence-based identification of fungi［J］. Mol Ecol， 2013， 22（21）：5271-5277.

Tuomisto H. A diversity of beta diversities： straightening up a concept gone awry. Part 1. Defining beta diversity as a function of alpha and gamma diversity［J］. Ecography， 2010， 33（1）：2-22.

Zoetendal EG， Raes J， van den Bogert B， et al. The human small intestinal microbiota is driven by rapid uptake and conversion of simple carbohydrates［J］. ISME J， 2012， 6（7）：1415-1426.

Xi JX， Ding D， Zhu HW， et al. Disturbed microbial ecology in Alzheimer's disease： evidence from the gut microbiota and fecal metabolome［J］. BMC Microbiol， 2021， 21（1）：226.

Ji HF， Shen L. Probiotics as potential therapeutic options for Alzheimer's disease［J］. Appl Microbiol Biotechnol， 2021， 105（20）：7721-7730.

Liu J， Yu C， Li R， et al. High-altitude Tibetan fermented milk ameliorated cognitive dysfunction by modified gut microbiota in Alzheimer's disease transgenic mice［J］. Food Funct， 2020， 11（6）：5308-5319.

Yu M， Mu C， Zhang C， et al. Marked response in microbial community and metabolism in the ileum and cecum of suckling piglets after early antibiotics exposure［J］. Front Microbiol， 2018， 9：1166.

邓爱萍，刘焦，杨静，等. 帕金森病与阿尔茨海默病患者肠道菌群及炎症因子分析［J］. 胃肠病学和肝病学杂志，2021，30（1）：60-65.

Deng AP， Liu J， Yang Y， et al. Analysis of the level of inflammatory factors in serum and intestinal flora's changes in patients with Parkinson's disease and Alzheimer's disease［J］. Chin J Gastroenterol Hepatol， 2021， 30（1）：60-65.

Marion S， Desharnais L， Studer N， et al. Biogeography of microbial bile acid transformations along the murine gut［J］. J Lipid Res， 2020， 61（11）：1450-1463.

Mahmoudiandehkordi S， Arnold M， Nho K， et al. Altered bile acid profile associates with cognitive impairment in Alzheimer's disease-an emerging role for gut microbiome［J］. Alzheimers Dement， 2019， 15（1）：76-92.

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