中国比较医学杂志

自体粪菌移植对结肠肿瘤生长抑制及其紧密连接蛋白调控作用的实验研究

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任行 ¹ , 白净 ² , 张浚琪 ¹ , 叶学帅 ¹ , 檀梦天 ¹ , 孙宇航 ³ , 李磊 ⁴ , 付泽娴 ⁵^,^*

中国比较医学杂志 | 研究报告 2026,36(6): 31-40

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中国比较医学杂志 |研究报告 2026 , 36 (6) : 31 -40

自体粪菌移植对结肠肿瘤生长抑制及其紧密连接蛋白调控作用的实验研究

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任行¹, 白净², 张浚琪¹, 叶学帅¹, 檀梦天¹, 孙宇航³, 李磊⁴, 付泽娴⁵^,^*

作者信息

^1．河北工程大学临床医学院，河北邯郸 056038

^2．河北工程大学附属医院老年病科，河北邯郸 056002

^3．河北工程大学附属医院医学整形美容科，河北邯郸 056002

^4．河北工程大学附属医院普外中心，河北邯郸 056002

^5．河北工程大学医学院，河北邯郸 056038

通讯作者:

付泽娴（1980—），男，博士，副教授，硕士生导师，研究方向：胃肠道肿瘤免疫治疗，肠道菌群和肿瘤。E-mail: fuzexian@hebeu.edu.cn

作者简介:

任行（1998—），男，在读硕士研究生，研究方向：肠道菌群及胃肠肿瘤治疗。E-mail: 1443678414@qq.com

Experimental study on the inhibitory effect of autologous fecal microbiota transplantation on colon tumor growth and its regulatory effect on tight junction proteins

Hang REN¹, Jing BAI², Junqi ZHANG¹, Xueshuai YE¹, Mengtian TAN¹, Yuhang SUN³, Lei LI⁴, Zexian FU⁵^,^*

Affiliations

^1.School of Clinical Medicine, Hebei University of Engineering, Handan 056038, China

^2.Department of Geriatrics, Affiliated Hospital of Hebei University of Engineering, Handan 056002

^3.Medical Plastic Surgery and Cosmetic Center, Affiliated Hospital of Hebei University of Engineering, Handan 056002

^4.General Surgery Center, Affiliated Hospital of Hebei University of Engineering, Handan 056002

^5.School of Medicine, Hebei University of Engineering, Handan 056038

出版时间: 2026-03-30 doi: 10.3969/j.issn.1671-7856.2026.06.004

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摘要

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目的

通过自体粪菌移植（AFMT）干预，观察氧化偶氮甲烷（AOM）/葡聚糖硫酸钠（DSS）诱导的结肠炎相关结直肠癌（CAC）小鼠结肠肿瘤情况，探究AFMT通过影响紧密连接蛋白发挥的抑瘤作用及其机制。方法SPF级雌性BALB/c小鼠随机分为空白对照组、CAC模型组和AFMT干预组，每组8只。CAC模型组按照10 mg/kg腹腔注射AOM 1次，连续饮用3.5% DSS 7 d，连续饮用0% DSS 14 d，为1个循环，共计3个循环，构建CAC模型；AFMT干预组在构建CAC模型时同步给予0.1 mL自体菌液隔天灌胃至循环结束；空白对照组无特殊处理。观察小鼠基本情况并记录体质量。实验结束后测量结肠长度和记录肿瘤数目，进行结肠病理学检查，使用Western blot和RT-qPCR检测结肠组织Occludin（OCLN）、Claudin-1（CLDN1）的mRNA和蛋白表达水平，同时采用16S rRNA测序技术对各组小鼠粪便样本菌群进行鉴定分析。

结果

与空白对照组相比，CAC模型组结肠长度显著缩短（P<0.0001），肿瘤数目明显增多。经AFMT干预后，小鼠结肠长度缩短减轻（P<0.01），肿瘤数目减少（P<0.05）。小鼠结肠组织学检查可见CAC模型组结肠隐窝结构扭曲，杯状细胞减少，炎性细胞数量增加（P<0.01），经AFMT干预后，隐窝结构和杯状细胞有所改善，炎性细胞减少（P<0.05）。与空白对照组相比，CAC模型组小鼠结直肠肿瘤组织中Occludin和Claudin-1的蛋白表达水平显著降低（P<0.05，P<0.01），经AFMT干预后结直肠肿瘤组织中Occludin、Claudin-1的蛋白表达水平显著上升（P<0.05）。与空白对照组相比，CAC模型组中OCLN和CLDN1的mRNA表达水平显著下调（P<0.05）；经AFMT干预后，其mRNA表达水平显著回升（P<0.05）。与空白对照组相比，AFMT干预组厚壁菌门（Firmicutes）和拟杆菌门（Bacteroidota）相对丰度差异无统计学意义（P>0.05），CAC模型组Firmicutes相对丰度降低（P<0.05），Bacteroidota相对丰度增高（P<0.05）。结论AFMT干预可恢复肠道Firmicutes相对丰度，降低Bacteroidota相对丰度，有效改善肿瘤环境中紧密连接蛋白的异常表达，修复肠道屏障，从而调节肠道屏障功能，改善肠道炎症，有效缓解CAC病理进程。

关键词

自体粪菌移植 / 结肠炎相关结直肠癌 / 肠道菌群 / Occludin / Claudin-1

Abstract

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Objective

To observe colon tumor status in mice with azoxymethane/dextran sodium sulfate (AOM/DSS) -induced colitis-associated colorectal cancer (CAC) following autologous fecal microbiota transplantation (AFMT), and to investigate the anti-tumor effects and underlying mechanism of AFMT through its influence on tight junction proteins.

Methods

Female specific-pathogen-free BALB/c mice were divided randomly into blank control, CAC model, and AFMT intervention groups (n = 8 per group). CAC model mice received a single intraperitoneal injection of AOM (10 mg/kg), followed by drinking water containing 3.5% DSS for 7 days, followed by 0% DSS for 14 days, constituting one cycle; three cycles were performed to establish the CAC model. Mice in the AFMT group received daily AFMT (0.1 mL autologous fecal suspension) via gavage every other day concurrent with the CAC modeling protocol until cycle completion. Control mice received no special treatment. The general condition and body weight of the mice were monitored. Upon completion of the experiment, colon length was measured, tumor numbers were recorded, and colon pathology was examined. mRNA and protein expression levels of the tight junction proteins Occludin (OCLN) and Claudin-1 (CLDN1) in colorectal tumor tissue were detected by reverse transcription-polymerase chain reaction and Western blot, respectively. The fecal microbiota composition in each group was analyzed using 16S rRNA gene sequencing.

Results

Compared with the blank control group, the CAC model group showed significantly shortened colon length (P< 0.0001) and a marked increase in tumor number. After AFMT intervention, the shortening of colon length was alleviated (P<0.01), and the number of tumors was reduced (P<0.05). Histological examination of mouse colon tissues revealed distorted crypt structures, reduced goblet cells, and increased inflammatory cell infiltration in the CAC model group(P< 0.01). After AFMT intervention, the crypt structure and goblet cells improved, and inflammatory cells decreased (P<0.05). Compared with the blank control group, the protein expression levels of Occludin and Claudin-1 in colorectal tumor tissues of the CAC model group were significantly decreased (P<0.05, P<0.01). After AFMT intervention, the protein expression levels of Occludin and Claudin-1 in colorectal tumor tissues significantly increased (P<0.05). As compared to the blank control group, the mRNA expression levels of OCLN and CLDN1 in the CAC model group were significantly downregulated (P <0.05); after AFMT intervention, their mRNA expression levels significantly recovered (P< 0.05). Compared with the blank control group, there was no statistically significant difference in the relative abundance of Firmicutes and Bacteroidota in the AFMT intervention group (P < 0.05). In the CAC model group, the relative abundance of Firmicutes decreased (P<0.05), while the relative abundance of Bacteroidota increased (P<0.05). Conclusions AFMT intervention can restore the relative abundance of Firmicutes and reduce the relative abundance of Bacteroroidota in the gut, effectively improve the aberrant expression of tight junction proteins within the tumor microenvironment, repair the intestinal barrier, regulate intestinal barrier function, alleviate intestinal inflammation, and consequently mitigate the pathological progression of CAC.

Key words

autologous fecal microbiota transplantation / colitis-associated colorectal cancer / intestinal microbiota / Occludin / Claudin-1

引用本文

任行, 白净, 张浚琪, 叶学帅, 檀梦天, 孙宇航, 李磊, 付泽娴. 自体粪菌移植对结肠肿瘤生长抑制及其紧密连接蛋白调控作用的实验研究. 中国比较医学杂志, 2026 , 36 (6) : 31 -40 . DOI: 10.3969/j.issn.1671-7856.2026.06.004

Hang REN, Jing BAI, Junqi ZHANG, Xueshuai YE, Mengtian TAN, Yuhang SUN, Lei LI, Zexian FU. Experimental study on the inhibitory effect of autologous fecal microbiota transplantation on colon tumor growth and its regulatory effect on tight junction proteins[J]. Chinese Journal of Comparative Medicine, 2026 , 36 (6) : 31 -40 . DOI: 10.3969/j.issn.1671-7856.2026.06.004

基金

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河北省教育厅科学研究项目(ZD2022039)
河北省三三三人才工程项目(C20231057)

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2026年第36卷第6期

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doi: 10.3969/j.issn.1671-7856.2026.06.004

接收时间：2025-08-04
首发时间：2026-08-05
出版时间：2026-03-30

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收稿日期：2025-08-04

基金

河北省教育厅科学研究项目(ZD2022039)

河北省三三三人才工程项目(C20231057)

作者信息

^1．河北工程大学临床医学院，河北邯郸 056038

^2．河北工程大学附属医院老年病科，河北邯郸 056002

^3．河北工程大学附属医院医学整形美容科，河北邯郸 056002

^4．河北工程大学附属医院普外中心，河北邯郸 056002

^5．河北工程大学医学院，河北邯郸 056038

通讯作者:

付泽娴（1980—），男，博士，副教授，硕士生导师，研究方向：胃肠道肿瘤免疫治疗，肠道菌群和肿瘤。E-mail: fuzexian@hebeu.edu.cn

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https://castjournals.cast.org.cn/joweb/zgbjyxzz/CN/10.3969/j.issn.1671-7856.2026.06.004

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2种不同金属材料的力学参数

科 Family	属数 Number of genus	种数 Number of species	占总种数比例 Percentage of total species (%)	属 Genus	种数 Number of species	占总种数比例 Percentage of total species (%)
鹅膏菌科Amanitaceae	2	11	5.26	鹅膏菌属 Amanita	10	4.78
小菇科 Mycenaceae	2	12	5.74	丝盖伞属 Inocybe	5	2.39
多孔菌科 Polyporaceae	8	14	6.70	蜡蘑属 Laccaria	5	2.39
红菇科 Russulaceae	3	23	11.00	小皮伞属 Marasmius	6	2.87
				小菇属 Mycena	11	5.26
				光柄菇属 Pluteus	5	2.39
				红菇属 Russula	17	8.13
				栓菌属 Trametes	5	2.39

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