Effects of fecal microbiota transplantation on inflammatory responses， microbiota composition，and metabolites in mice with delayed neurocognitive recovery

Tang Lu; Zhang Binsen; Zhang Xiaojia; Song Wenjing; Du Zhongying; Wang Chunai

doi:10.13406/j.cnki.cyxb.003699

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Effects of fecal microbiota transplantation on inflammatory responses， microbiota composition，and metabolites in mice with delayed neurocognitive recovery

Basic research | 更新时间：2025-10-23

- Effects of fecal microbiota transplantation on inflammatory responses， microbiota composition，and metabolites in mice with delayed neurocognitive recovery
- Journal of Chongqing Medical University Vol. 50, Issue 1, Pages: 44-51(2025)
- 作者机构：
  
  1.甘肃中医药大学第一临床医学院，兰州 730030
  2.重庆医科大学第五临床学院，重庆 404100
  3.甘肃省中医院麻醉疼痛医学中心，兰州 730030
- 作者简介：
- 基金信息：
- DOI：10.13406/j.cnki.cyxb.003699
  CLC： R619
- Received：12 January 2024，
  
  Revised：2024-02-29，
  
  Accepted：27 May 2024，
  
  Published：28 January 2025
- 稿件说明：
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唐璐,张斌森,张笑佳,等.菌群移植对神经认知恢复延迟小鼠炎症反应以及菌群和代谢产物的研究[J].重庆医科大学学报,2025,50(1):44-51.

Tang Lu,Zhang Binsen,Zhang Xiaojia,et al.Effects of fecal microbiota transplantation on inflammatory responses， microbiota composition，and metabolites in mice with delayed neurocognitive recovery[J].Journal of Chongqing Medical University,2025,50(1):44-51.
唐璐,张斌森,张笑佳,等.菌群移植对神经认知恢复延迟小鼠炎症反应以及菌群和代谢产物的研究[J].重庆医科大学学报,2025,50(1):44-51. DOI： 10.13406/j.cnki.cyxb.003699.

Tang Lu,Zhang Binsen,Zhang Xiaojia,et al.Effects of fecal microbiota transplantation on inflammatory responses， microbiota composition，and metabolites in mice with delayed neurocognitive recovery[J].Journal of Chongqing Medical University,2025,50(1):44-51. DOI： 10.13406/j.cnki.cyxb.003699.

摘要

目的

探讨粪便菌群移植（fecal microbiota transplantation，FMT）对神经认知恢复延迟（delayed neurocognitive recovery，dNCR）小鼠认知能力、肠道菌群及代谢物和炎症反应的影响，为dNCR患者提供一种有效治疗方式。

方法

将小鼠随机分为对照组、模型组和菌群移植组3组。采用胫骨中段骨折的方式建立dNCR模型，收集健康小鼠粪便进行FMT。采用Morris水迷宫实验和旷场实验检测行为学能力，Elisa法检测海马和血清中白细胞介素（interleukin，IL）-6、IL-1β和肿瘤坏死因子-α（tumor necrosis factor，TNF-α）的含量，Western blot法检测结肠组织紧密连接蛋白-1（zonula occludens protein 1，ZO-1）及海马神经元特异性烯醇化酶（neuron-specific enolase，NSE）和中枢神经特异性蛋白β（S100 Calcium-binding protein，S-100β）的蛋白含量。透射电镜下观察海马区神经细胞超微结构。采用16s rRNA基因测序以及液相色谱-质谱联用技术来检测肠道菌群及代谢物的变化。

结果

旷场实验和水迷宫实验结果显示模型组认知功能受损而菌群移植后改善了认知损害。模型组血清以及海马中IL-6、IL-1β和TNF-α高于其他2组。模型组结肠组织中ZO-1蛋白含量低于其他2组（

=0.000），而NSE及S-100β高于对照组和菌群移植组（

=0.000）。透射电镜结果显示模型组海马组织结构破坏，而菌群移植后改善了这些变化。3组之间的Chao 1指数和Shannon指数相似。基于bray_curtis的PCoA发现模型组与对照组、菌群移植组明显分离。模型组和菌群移植组的优势菌以拟杆菌门、厚壁菌门为主，模型组中厚壁菌、脱硫弧菌和变形杆菌高于另两组，而拟杆菌降低。代谢分析中PLS-DA分析显示3组明显分离。热图显示出模型组与对照组、菌群移植的明显差别，与对照组和菌群移植组相比，模型组中色氨酸、5-羟色胺、吲哚等代谢物含量减少，而溶血磷脂酰胆碱增加。

结论

肠道菌群及代谢产物的失调以及炎性反应可能是dNCR发生发展的重要机制，而FMT可能通过这机制能够改善麻醉/手术后小鼠的认知功能。

Abstract

Objective

To investigate the effects of fecal microbiota transplantation（FMT） on the cognitive ability，microbiota composition，metabolites，and inflammatory response of mice with delayed neurocognitive recovery（dNCR），and to provide insights into the development of effective treatments for dNCR patients.

Methods

Mice were randomly divided into the control group，model group，and FMT group. The dNCR model was established by middle tibial fracture，and fecal samples were collected from healthy mice for FMT. Cognitive ability was assessed using the Morris water maze test（MWMT） and open field test（OFT）. IL-6，IL-1β and TNF-α levels in the hippocampus and serum were measured using ELISA. Colonic Z0-1 and hippocampal NSE and S-100β protein expression was measured by Western blot. The microbiota composition and changes in metabolites were examined using 16s rRNA sequencing and LC-MS，respectively.

Results

OFT and MWMT showed that model mice had cognitive impairment，which was attenuated in FMT mice. Serum and hippocampal levels of IL-6，IL-β and TNF-α were higher in the model group than in the other two groups. In addition，the model group had significantly lower colonic ZO-1 protein expression（

=0.000） but significantly higher hippocampal NSE and S-100β protein expression than the other two groups（

=0.000）. The Chao1 index and Shannon index were similar among the three groups. Principle coordinates analysis using Bray-Curtis dissimilarity revealed that the microbiota composition of model group was markedly distinct from those of the control and FMT groups. Bacteroidetes and Firmicutes were the predominant phyla in the model and FMT groups. The model group also had higher abundance of Firmicutes，Desulfobacterota，and Proteobacteria and lower abundance of Bacteroides than the control group and FMT group. Partial least-squares discriminant analysis demonstrated that the model group had a distinct metabolite composition than the other two groups，characterized by decreased tryptophan，5-hydroxytryptophan，and indole，as well as increased lysophosphatidylcholine.

Conclusion

Dysregulated microbiota and metabolites as well as inflammatory responses may be the key mechanisms driving dNCR development and progression. FMT can act on these pathways to improve the cognitive function of anesthetized or operated mice.

关键词

Keywords

references

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