Role of gut microbiota in homeostatic maintenance and promoting regeneration of radiosensitive tissues in mice following radiation exposure

Zhenni XU; Jing OU; Lingxiao HUANG; Xudan LEI; Fengchao WANG; Junping WANG; Yongping SU; Yu WANG; Dengqun LIU

doi:10.16016/j.1000-5404.202005197

您当前的位置：

首页 >

文章列表页 >

Role of gut microbiota in homeostatic maintenance and promoting regeneration of radiosensitive tissues in mice following radiation exposure

Basic Medicine | 更新时间：2026-01-09

- Role of gut microbiota in homeostatic maintenance and promoting regeneration of radiosensitive tissues in mice following radiation exposure
- Journal of Third Military Medical University Vol. 42, Issue 20, Pages: 1978-1986(2020)
- 作者机构：
  
  1.610041 成都，四川省肿瘤医院·研究所，四川省癌症防治中心，电子科技大学医学院，放射肿瘤学四川省重点实验室
  2.400038 重庆，陆军军医大学(第三军医大学)军事预防医学系：防原医学教研室，全军复合伤研究所，创伤、烧伤与复合伤国家重点实验室，重庆市纳米医学工程研究中心
  3.400038 重庆，陆军军医大学(第三军医大学)军事预防医学系：火箭军医学教研室
- 作者简介：
- 基金信息：
  
  the General Program of National Natural Science Foundation of China(81673089);the General Program of National Natural Science Foundation of China(81874255);the Applied Basic Science Research Plan of Science and Technology Department of Sichuan Province(2020YJ0458);the Research Program of Sichuan Cancer Hospital(YBR2019003)
- DOI：10.16016/j.1000-5404.202005197
  CLC： R322.45;R331.22;R818.03
- Received：21 May 2020，
  
  Revised：2020-07-20，
  
  Published：30 October 2020
- 稿件说明：
移动端阅览
Zhenni XU, Jing OU, Lingxiao HUANG, et al. Role of gut microbiota in homeostatic maintenance and promoting regeneration of radiosensitive tissues in mice following radiation exposure[J]. Journal of Third Military Medical University, 2020, 42(20): 1978-1986.
DOI：

Zhenni XU, Jing OU, Lingxiao HUANG, et al. Role of gut microbiota in homeostatic maintenance and promoting regeneration of radiosensitive tissues in mice following radiation exposure[J]. Journal of Third Military Medical University, 2020, 42(20): 1978-1986. DOI： 10.16016/j.1000-5404.202005197.

摘要

目的

探讨肠道菌群(gut microbiota

GM)对小鼠骨髓造血和肠上皮稳态维持及放射损伤修复的影响。

方法

6~8周龄C57BL/6J小鼠分为2组:Abx组饮用抗生素(antibiotics

Abx)饮水清除GM；对照组给予正常饮水。测定实验后21 d小鼠体质量等基础状况改变。检测外周血和骨髓HE染色评估清除GM对骨髓造血稳态维持的影响；HE染色、BrdU免疫组化、qPCR、类器官培养等方法评估清除GM对肠道干细胞稳态的影响。8 Gy全身照射小鼠后3、7 d

取材小肠，通过形态学和组织染色评估清除GM对小鼠全身放射损伤后骨髓造血和肠道再生修复过程的影响。

结果

清除GM后21 d，Abx组小鼠体质量较对照组显著降低(

＜0.01)；外周血中白细胞、红细胞、血红蛋白和血小板水平出现明显波动，小鼠骨髓巨核细胞计数

较对照组显著增加(

＜0.01)。与对照组比较，清除GM后21 d，Abx组小肠隐窝缩短，BrdU阳性隐窝细胞减少，Lgr5、Olfm4、Axin2等肠干细胞相关基因mRNA水平显著下降，肠隐窝形成类器官能力降低(

＜0.05)。8 Gy放射损伤后，Abx组小鼠存活时间较对照组显著缩短(

＜0.01)，同时骨髓和小肠再生速度减缓。放射损伤后7 d，Abx组小肠绒毛中杯状细胞数量显著增多，隐窝中内分泌肠上皮细胞显著减少。

结论

肠道菌群有助于维持小鼠骨髓造血和肠道干细胞稳态，并促进放射损伤后骨髓造血重建和肠道再生修复。

Abstract

Objective

To investigate the role of gut microbiota (GM) in maintaining hematopoietic function and intestinal epithelial homeostasis function and promoting regeneration of hematopoietic tissues and intestinal epithelium in mice radiation exposure.

Methods

C57BL/6J mice (6~8 weeks) were treated with antibiotics added in drinking water for 21 d to deplete the GM (Abx group)

and the control mice were given normal drinking water. The changes in body weight and general condition of the mice were recorded. The effect of GM depletion on hematopoietic homeostasis was evaluated by peripheral blood analysis and HE staining of the bone marrow

and the changes in intestinal homeostasis were determined with HE staining

BrdU immunohistochemistry

RT-qPCR

and enteroid culture. The mice with or without GM depletion were subjected to X-ray exposure at the total body irradiation (TBI) dose of 8 Gy

and the regeneration of the radiosensitive tissues were assessed at 3 and 7 d after the exposure.

Results

GM depletion induced by 21-day treatment with antibiotics resulted in severe weight loss of the mice (

0.01) and significant changes in peripheral white blood cells (WBC)

red blood cells (RBC)

hemoglobin and platelets

and markedly increased number of megakaryocytes in the bone marrow (

0.01). GM depletion induced an obvious decrease in crypt depth and the number of BrdU

cryptal cells and significantly down-regulated the expression of intestinal stem cell-relat

ed genes including Lgr5

Olfm4

and Axin2. The mice with GM depletion showed significantly lowered enteroid formation capacity (

0.05) and shortened survival (

0.01) with obviously lowered rate of hematopoietic and intestinal tissue regeneration after radiation exposure. At 7 d after the radiation

the mice with GM depletion showed increased villous goblet cells and decreased cryptal enteroendocrine cells in the intestines.

Conclusion

Normally functioning GM are essential for maintaining hematopoietic and intestinal stem cell homeostasis and promoting regeneration of the radiosensitive tissues after radiation exposure.

关键词

Keywords

references

FERREIRA M R, ANDREYEV H J N. Editorial: Gut microbiota and chemotherapy- or radiation-induced gastrointestinal mucositis[J]. Aliment Pharmacol Ther, 2014, 40(6): 733-734. DOI: 10.1111/apt.12905.

TROMPETTE A, GOLLWITZER E S, YADAVA K, et al. Gut microbiota metabolism of dietary fiber influences allergic airway disease and hematopoiesis[J]. Nat Med, 2014, 20(2): 159-166. DOI: 10.1038/nm.3444.

MA E L, SMITH A, DESAI N, et al. Bidirectional brain-gut interactions and chronic pathological changes after traumatic brain injury in mice[J]. Brain Behav Immun, 2017, 66: 56-69. DOI: 10.1016/j.bbi.2017.06.018.

KIM M S, KIM Y, CHOI H, et al. Transfer of a healthy microbiota reduces amyloid and tau pathology in an Alzheimer's disease animal model[J]. Gut, 2020, 69(2): 283-294. DOI: 10.1136/gutjnl-2018-317431.

CARR J S, KING S, DEKANEY C M. Depletion of enteric bacteria diminishes leukocyte infiltration following doxorubicin-induced small intestinal damage in mice[J]. PLoS ONE, 2017, 12(3): e0173429. DOI: 10.1371/journal.pone.0173429.

CUI M, XIAO H W, LI Y, et al. Faecal microbiota transplantation protects against radiation-induced toxicity[J]. EMBO Mol Med, 2017, 9(4): 448-461. DOI: 10.15252/emmm.201606932.

徐珍妮, 欧静, 王钰, 等. Lewis肺腺癌对小鼠肠道干细胞及其微环境的影响[J].第三军医大学学报, 2020, 42(12): 1155-1162. DOI: 10.16016/j.1000-5404.202002046.

XU Z N, OU J, WANG Y, et al. Effect of Lewis lung cancer on mouse intestinal stem cells and their microenvironment [J]. J Third Mil Med Univ, 2020, 42(12): 1155-1162. DOI: 10.16016/j.1000-5404.202002046.

ROUTY B, DEROSA L, DUONG C P M, et al. Gut microbiome influences efficacy of PD-1-based immunotherapy against epithelial tumors[J]. Science, 2018, 359(6371): 91-97. DOI: 10.1126/science.aan3706.

JOSEFSDOTTIR K S, BALDRIDGE M T, KADMON C S, et al. Antibiotics impair murine hematopoiesis by depleting the intestinal microbiota[J]. Blood, 2017, 129(6): 729-739. DOI: 10.1182/blood-2016-03-708594.

LEE S, KIM H, YOU G, et al. Bone marrow CX3CR1+ mononuclear cells relay a systemic microbiota signal to control hematopoietic progenitors in mice[J]. Blood, 2019, 134(16): 1312-1322. DOI: 10.1182/blood.2019000495.

KAIKO G E, RYU S H, KOUES O I, et al. The colonic crypt protects stem cells from microbiota-derived metabolites[J]. Cell, 2016, 165(7): 1708-1720. DOI: 10.1016/j.cell.2016.05.018

MENENDEZ A, WILLING B P, MONTERO M, et al. Bacterial stimulation of the TLR-MyD88 pathway modulates the homeostatic expression of ileal Paneth cell α-defensins[J]. J Innate Immun, 2013, 5(1): 39-49. DOI: 10.1159/000341630.

SATO T, VAN ES J H, SNIPPERT H J, et al. Paneth cells constitute the niche for Lgr5 stem cells in intestinal crypts[J]. Nature, 2011, 469(7330): 415-418. DOI: 10.1038/nature09637.

AMCHESLAVSKY A, SONG W, LI Q, et al. Enteroendocrine cells support intestinal stem-cell-mediated homeostasis in Drosophila[J]. Cell Rep, 2014, 9(1): 32-39. DOI: 10.1016/j.celrep.2014.08.052.

MURATA K, JADHAV U, MADHA S, et al. Ascl2-dependent cell dedifferentiation drives regeneration of ablated intestinal stem cells[J]. Cell Stem Cell, 2020, 26(3): 377-390.e6. DOI: 10.1016/j.stem.2019.12.011.

Views

下载量

CSCD

Alert me when the article has been cited

提交

Tools

Publicity Resources

Berberine improves drug-induced liver injury in mice by modulating gut microbiota

Time-restricted feeding attenuates DSS-induced colitis in mice by modulating regenerating islet-derived protein 3 gamma and gut microbiota

Effects of long-term 2.65 GHz radiofrequency radiation on inflammatory response and intestinal microbiota in mice

Characteristics of gut microbiota in people with circadian rhythm disruption and its correlation with cognition

胆囊切除术与肠道菌群组成及其功能变化关系的研究

Related Author

TU Dianji

ZHOU Jiyin

FENG Xiaojie

LEI Yuanyuan

FENG Yunxuan

CHENG Lulu

WANG Yingjie

XI Changqi

Related Institution

Clinical Medical Research Center， Second Affiliated Hospital， Army Medical University （Third Military Medical University）

Department of Gastroenterology， Second Affiliated Hospital， Army Medical University （Third Military Medical University）

School of Animal Science and Technology， Foshan University

Academy of Military Medical Sciences， Academy of Military Science

⁰