食品科学 ›› 2025, Vol. 46 ›› Issue (13): 133-117.doi: 10.7506/spkx1002-6630-20241225-211

• 营养卫生 • 上一篇    

两歧双歧杆菌CCFM1389通过修复肠神经和肠道屏障调节肠道运动障碍

黄尹,李嘉臻,刘文续,薛伊凡,朱胜男,王琳琳,王刚   

  1. (江南大学食品学院,江苏 无锡 214122)
  • 发布日期:2025-06-13
  • 基金资助:
    国家自然科学基金面上项目(32472348)

Bifidobacterium bifidum CCFM1389 Regulates Intestinal Motility Disorder by Repairing the Enteric Nervous System and Intestinal Barrier

HUANG Yin, LI Jiazhen, LIU Wenxu, XUE Yifan, ZHU Shengnan, WANG Linlin, WANG Gang   

  1. (School of Food Science and Technology, Jiangnan University, Wuxi 214122, China)
  • Published:2025-06-13

摘要: 利用广谱抗生素(broad-spectrum antibiotics,ABX)构建伪无菌小鼠模型,探究其对小鼠肠道运动和肠神经系统(enteric nervous system,ENS)的影响。以两歧双歧杆菌CCFM1167为阳性菌株,另从4 株两歧双歧杆菌中筛选并评估不同菌株对的肠道功能障碍及ENS的调节作用。通过使用16S rDNA测序技术检测肠道微生物群的变化,运用苏木精-伊红染色和实时聚合酶链式反应技术表征ENS和肠屏障的损伤情况。研究结果表明,ABX处理显著影响小鼠肠道结构和功能,表现为肠道形态的改变、肠道蠕动减慢以及粪便含水率增加,且肠道微生态严重失衡,伴随着ENS和肠屏障的损伤。应用两歧双歧杆菌进行干预后,发现两歧双歧杆菌CCFM1389显著缩短了肠道转运时间,将粪便含水率调整至接近正常对照组,有效调节了肠道运动障碍。此外,CCFM1389显著提高了结肠神经元特异性标志物PGP9.5和肠神经胶质细胞特异性标志物S100β和GFAP的基因表达水平,表明其对ENS具有修复作用。CCFM1389还显著提高紧密连接蛋白基因(Occludin、Claudin-3、ZO-1)的表达水平,从而改善肠道屏障的损伤,且效果优于阳性菌株CCFM1167。肠道菌群分析结果显示,CCFM1389调节小鼠肠道微生物群的结构和组成,维护肠道微生态平衡。Spearman相关性分析表明,CCFM1389有效调节ABX诱导的肠道运动障碍,其机制可能是通过增加有益菌Akkermansia、Bifidobacterium、Lachnoclostridium的相对丰度,同时降低致病菌Escherichia_Shigella、Enterococcus的相对丰度,从而修复ENS和肠道屏障,调节肠道运动。

关键词: 肠道运动障碍;肠道菌群;两歧双歧杆菌;肠屏障;肠神经

Abstract: A pseudo-germ-free mouse model was constructed using broad-spectrum antibiotics (ABX) to investigate their effects on intestinal motility and the enteric nervous system (ENS) in mice. Bifidobacterium bifidum CCFM1167 was used as a positive strain, and another four B. bifidum strains were screened and evaluated for their regulatory effects on intestinal dysfunction and the ENS. 16S rDNA gene sequencing was used to detect changes in the gut microbiota, and hematoxylin-eosin (H&E) staining and real-time polymerase chain reaction (PCR) were employed to characterize the damage of the ENS and the intestinal barrier. The results showed that ABX treatment significantly affected the intestinal structure and function of mice, leading to altered intestinal morphology, slowed motility and increased fecal water content, accompanied by a severe imbalance in the gut microbiota and damage to the ENS and the intestinal barrier. After intervention with B. bifidum CCFM1389, a significant reduction in total intestinal transit time was observed, and fecal water content returned close to the normal level, along with the alleviation of intestinal motility disorders. Additionally, CCFM1389 significantly increased the gene expression levels of specific markers for colonic neurons (PGP9.5) and enteric glial cells (S100β and GFAP), indicating a repairing effect on the ENS. CCFM1389 also significantly elevated the gene expression of tight junction proteins (Occludin, Claudin-3 and ZO-1), alleviating intestinal barrier damage, and its effect was more pronounced than that of the positive strain CCFM1167. Furthermore, CCFM1389 regulated the structure and composition of the gut microbiota, maintaining intestinal microbial homeostasis. Spearman correlation analysis indicated that CCFM1389 effectively modulated ABX-induced intestinal motility disorders, possibly by increasing the increase in the relative abundance of beneficial bacteria such as Akkermansia, Bifidobacterium, and Lachnoclostridium while decreasing the relative abundance of pathogenic bacteria such as Escherichia_Shigella and Enterococcus, thereby repairing the ENS and the intestinal barrier and regulating intestinal motility.

Key words: intestinal motility disorder; intestinal flora; Bifidobacterium bifidum; intestinal barrier; enteric nerves

中图分类号: