Autologous fecal microbiota transplantation attenuates colitis-associated carcinogenesis in mice by suppressing NF-κB signaling and restoring CD8⁺ T cell/regulatory T cell balance

REN Hang; BAI Jing; YE Xueshuai; LIU Guoqiang; ZHANG Junqi; YANG Yong; TAN Mengtian; LI Lei; FU Zexian

doi:10.16016/j.2097-0927.202511026

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Autologous fecal microbiota transplantation attenuates colitis-associated carcinogenesis in mice by suppressing NF-κB signaling and restoring CD8⁺ T cell/regulatory T cell balance

Basic Medicine | 更新时间：2026-02-23

- Autologous fecal microbiota transplantation attenuates colitis-associated carcinogenesis in mice by suppressing NF-κB signaling and restoring CD8⁺ T cell/regulatory T cell balance
- Journal of Army Medical University Vol. 48, Issue 3, Pages: 294-304(2026)
- 作者机构：
  
  1.河北工程大学临床医学院，河北邯郸
  4.河北工程大学医学院河北邯郸
  2.河北工程大学老年病科，河北邯郸
  3.河北工程大学胃肠外科，河北邯郸
- 作者简介：
- 基金信息：
  
  the Three-Three-Three Talent Project of Hebei Province(C20231057);the Scientific Research Project of Higher Education Institutions in Hebei Province(ZD2022039);the Innovation and Cultivation Fund Project of Hebei University of Engineering （2024）. Corresponding author： FU Zexian, E-mail： fuzexian@hebeu.edu.cn(2024)
- DOI：10.16016/j.2097-0927.202511026
  CLC： R378.2;R73-362;R735.35
- Received：05 November 2025，
  
  Revised：2026-01-12，
  
  Accepted：14 January 2026，
  
  Published：15 February 2026
- 稿件说明：
移动端阅览
任行，白净，叶学帅，等.自体粪菌移植通过重塑菌群抑制NF-κB通路并调节CD8⁺ T/Treg平衡抑制小鼠结肠炎相关性结肠癌［J］.陆军军医大学学报，2026，48（03）：294-304.DOI：10.16016/j.2097-0927.202511026.

REN H，BAI J，YE X S，et al.Autologous fecal microbiota transplantation attenuates colitis-associated carcinogenesis in mice by suppressing NF-κB signaling and restoring CD8⁺ T cell/regulatory T cell balance［J］.J Army Med Univ，2026，48（03）：294-304.DOI：10.16016/j.2097-0927.202511026.
任行，白净，叶学帅，等.自体粪菌移植通过重塑菌群抑制NF-κB通路并调节CD8⁺ T/Treg平衡抑制小鼠结肠炎相关性结肠癌［J］.陆军军医大学学报，2026，48（03）：294-304.DOI：10.16016/j.2097-0927.202511026. DOI：

REN H，BAI J，YE X S，et al.Autologous fecal microbiota transplantation attenuates colitis-associated carcinogenesis in mice by suppressing NF-κB signaling and restoring CD8⁺ T cell/regulatory T cell balance［J］.J Army Med Univ，2026，48（03）：294-304.DOI：10.16016/j.2097-0927.202511026. DOI：

摘要

目的

探讨自体粪菌移植（autologous fecal microbiota transplantation，AFMT）通过调节核因子κB（nuclear factor kappa-B，NF-κB）信号通路对氧化偶氮甲烷（azoxymethane，AOM）/葡聚糖硫酸钠（dextran sulfate sodium salt，DSS）诱导的结肠炎相关性结肠癌（colitis-associated colorectal cancer，CAC）模型小鼠免疫功能及肿瘤抑制作用的影响。

方法

将6周龄（specific pathogen free，SPF）级BALB/c雌性小鼠［体质量（20±2）g］按照随机数字表法分为3组（

=5）：空白对照组（Con组）、CAC模型组（Mod组）和AFMT干预组（AFMT组）。采用单次腹腔注射AOM（10 mg/kg）并联合3轮DSS循环处理（3.5%DSS自由饮用7 d和纯净水恢复14 d）建立CAC模型；AFMT组于建模后第7天起隔日灌胃0.1 mL自体粪菌悬液，直至实验结束；其余组灌胃等量无菌生理盐水。实验结束后采集结直肠、脾脏、血清及粪便样本，通过HE染色评估结肠组织病理损伤及炎症细胞浸润程度。Western blot检测结肠组织中NF-κB p65和p-NF-κB p65蛋白表达；ELISA检测各组小鼠血清肿瘤坏死因子-α（tumor necrosis factor-α，TNF-α）水平；流式细胞术分析脾脏中CD8⁺ T和Treg（CD4

CD25

Foxp3

）的细胞比例，16S rRNA测序分析肠道菌群组成、α多样性与β多样性。

结果

与Con组比较，Mod组结肠HE染色显示杯状细胞减少，炎性细胞浸润明显，小鼠结肠组织中p-NF-κB p65与NF-κB p65的比例上升（

0.05），血清中TNF-α炎症因子水平升高（

0.001），脾脏组织中CD8

T细胞比例下降（

0.001），Treg细胞比例升高（

0.05），拟杆菌目（

Bacteroidales

）的相对丰度升高（

0.05），乳杆菌目（

Lactobacillales

）相对丰度下降（

0.05）。与Mod组相比，AFMT组结肠组织结构损伤较轻，炎性细胞浸润减少，结肠组织中p-NF-κB p65与NF-κB p65的比值下降（

0.01），TNF-α炎症因子水平下降（

0.01），CD8

T细胞比例升高（

0.05），Treg细胞比例降低（

0.05），

Bacteroidales

的相对丰度下降（

0.05），

Lactobacillales

相对丰度升高（

0.05）。

结论

AFMT干预后可能通过恢复

Lactobacillales

的丰度，增强肠道屏障/产生短链脂肪酸，抑制NF-κB炎症通路、降低TNF-α水平、调节T细胞免疫平衡，有效缓解CAC模型小鼠的疾病进展。

Abstract

Objective

To investigate the effects of autologous fecal microbiota transplantation (AFMT) on immune regulation and tumor suppression in a murine model of colitis-associated colorectal cancer (CAC) induced by azoxymethane (AOM)/dextran sulfate sodium (DSS)

with mechanistic emphasis on NF-κB pathway inhibition and CD8⁺ T cell/regulatory T cell (Treg) balance modulation.

Methods

Six-week-old female BALB/c mice [SPF grade

body weight (20±2) g

]

were randomly divided into 3 groups (

=5 per group): control group (Con)

CAC model group (Mod)

and AFMT intervention group (AFMT). The CAC model was established by a single intraperitoneal injection of AOM (10 mg/kg) followed by three cycles of DSS treatment (each cycle: 3.5%DSS in drinking water for 7 d plus 14 d of recovery with sterile water). Starting from day 7 post-modeling

the AFMT group received 0.1 mL of autologous fecal microbiota suspension

via

oral gavage every other day until the end of the experiment; control groups received equal volumes of sterile saline. At endpoint

colorectal tissues

spleen

serum

and fecal samples were collected. Colonic pathological injury and inflammatory cell infiltration were assessed by hematoxylin-eosin (HE) staining. NF-κB p65 and p-NF-κB p65 protein expression in colon tissue was detected by Western blot. Serum TNF-α levels were measured by ELISA.

Flow cytometry was used to analyze the proportions of CD8

T cells and regulatory T cells (Treg

defined as CD4

CD25

Foxp3

) in the spleen. Gut microbiota composition and diversity (α- and β-diversity) were analyzed by 16S rRNA sequencing.

Results

Compared with the Con group

the Mod group showed a reduction in goblet cells and significant inflammatory cell infiltration in HE-stained colon sections

an increased ratio of p-NF-κB p65 to NF-κB p65 in colon tissue (

0.05)

elevated serum TNF-α levels (

0.001)

a decreased proportion of CD8⁺ T cells in the spleen (

0.001)

an increased proportion of Treg cells (

0.05)

an increased relative abundance of

Bacteroidales

(

0.05)

and a decreased relative abundance of

Lactobacillales

(

0.05). Compared with the Mod group

the AFMT group showed milder structural damage and reduced inflammatory cell infiltration in the colon

a decreased ratio of p-NF-κB p65 to NF-κB p65 in colon tissue (

0.01)

reduced serum TNF-α levels (

0.01)

an increased proportion of CD8⁺ T cells in the spleen (

0.05)

a decreased proportion of Treg cells (

0.05)

a decreased relative abundance of

Bacteroidales

(

0.05)

and an increased relative abundance of

Lactobacillales

(

0.05).

Conclusion

AFMT intervention may alleviate disease progression in CAC model mice through multiple mechanisms: restoring the abundance of

Lactobacillales

enhancing the intestinal barrier function and promoting short-chain fatty acid production

inhibiting the NF-κB inflammatory pathway

reducing TNF-α levels

and regulating T-cell immune balance.

关键词

Keywords

references

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