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1009924对葡聚糖硫酸钠(DSS)诱导的肠道炎症的缓解作用。

The mitigative effects of 1009924 on DSS-induced intestinal inflammation.

作者信息

Chen Yishu, Ma Yan, Leng Yang, Li Xiaoling, Qin Sishi, Li Xiaoyan, Zhang Zhao, Yu Huajun

机构信息

Laboratory Animal Center, Guangdong Medical University, Zhanjiang, China.

Guangdong Longseek Testing Co., Ltd., Guangzhou, China.

出版信息

Front Microbiol. 2025 Aug 8;16:1560441. doi: 10.3389/fmicb.2025.1560441. eCollection 2025.

DOI:10.3389/fmicb.2025.1560441
PMID:40862149
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12370734/
Abstract

INTRODUCTION

The gut microbiota plays a crucial role in the treatment of inflammatory bowel disease (IBD). Recent studies have shown that the abundance of is associated with host inflammatory bowel disease (IBD), yet its specific mechanism of action remains to be further investigated.

METHODS

The strain 1009924 ( 1009924) was isolated from fresh fecal samples, and its biological characteristics and genomic features were analyzed. In this study, a zebrafish intestinal inflammation model was established by induction with 0.5% dextran sulfate sodium (DSS) for 72 h to evaluate the effect of 1009924 on alleviating intestinal inflammation.

RESULTS

This strain 1009924 is a strict anaerobe, forming circular, off-white colonies on BHI medium. It is Gram-positive, arranged in chains, and field emission scanning electron microscopy revealed abundant surface folds and pilus structures, along with excellent acid and bile salt tolerance. Whole-genome sequencing showed a total gene length of 6.05 Mb, a GC content of 45.72%, and 5,214 coding genes with no virulence genes. KEGG database annotation indicated that its gene functions are mainly enriched in metabolic pathways, environmental information processing, and genetic information processing, with abundant gene clusters involved in lipid metabolism and short-chain fatty acid (SCFA) metabolic pathways. Compared with the DSS-induced enteritis model group, 1009924 inhibited reactive oxygen species (ROS) production and neutrophil accumulation in zebrafish intestines. Histopathological analysis confirmed that it alleviated DSS-induced intestinal tissue damage, such as increasing goblet cell numbers and improving intestinal villus architecture. Real-time quantitative polymerase chain reaction (RT-qPCR) analysis demonstrated that 1009924 suppressed the activation of the TLR4/NF-κB signaling pathway by downregulating the expression of TLR4, MyD88, and NF-κB genes, thereby reducing the expression of pro-inflammatory factors (IL-6, IL-12) and the immune factor IL-10. Additionally, metabolomic analysis revealed that 1009924 regulated intestinal metabolism by increasing SCFA levels, including butyric acid and isovaleric acid.

CONCLUSION

1009924 significantly alleviates DSS-induced intestinal inflammation in zebrafish by regulating ROS levels, inhibiting excessive immune and inflammatory responses, and improving SCFA metabolism, highlighting its potential as a candidate strain for IBD treatment.

摘要

引言

肠道微生物群在炎症性肠病(IBD)的治疗中起着关键作用。最近的研究表明,[菌株名称]的丰度与宿主炎症性肠病(IBD)相关,但其具体作用机制仍有待进一步研究。

方法

从新鲜粪便样本中分离出菌株1009924([菌株名称]1009924),并分析其生物学特性和基因组特征。在本研究中,通过用0.5%硫酸葡聚糖钠(DSS)诱导72小时建立斑马鱼肠道炎症模型,以评估[菌株名称]1009924对减轻肠道炎症的作用。

结果

该菌株1009924是严格厌氧菌,在BHI培养基上形成圆形、灰白色菌落。它是革兰氏阳性菌,呈链状排列,场发射扫描电子显微镜显示其表面有丰富的褶皱和菌毛结构,且具有出色的耐酸和耐胆盐能力。全基因组测序显示总基因长度为6.05 Mb,GC含量为45.72%,有5214个编码基因且无毒力基因。KEGG数据库注释表明其基因功能主要富集在代谢途径、环境信息处理和遗传信息处理方面,有丰富的基因簇参与脂质代谢和短链脂肪酸(SCFA)代谢途径。与DSS诱导的肠炎模型组相比,[菌株名称]1009924抑制了斑马鱼肠道中活性氧(ROS)的产生和中性粒细胞的积累。组织病理学分析证实它减轻了DSS诱导的肠道组织损伤,如增加杯状细胞数量和改善肠绒毛结构。实时定量聚合酶链反应(RT-qPCR)分析表明,[菌株名称]1009924通过下调TLR4、MyD88和NF-κB基因的表达抑制TLR4/NF-κB信号通路的激活,从而降低促炎因子(IL-6、IL-12)和免疫因子IL-10的表达。此外,代谢组学分析显示,[菌株名称]1009924通过增加SCFA水平(包括丁酸和异戊酸)来调节肠道代谢。

结论

1009924通过调节ROS水平、抑制过度的免疫和炎症反应以及改善SCFA代谢,显著减轻了DSS诱导的斑马鱼肠道炎症,突出了其作为IBD治疗候选菌株的潜力。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f690/12370734/00b22f3bf2d6/fmicb-16-1560441-g0006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f690/12370734/2567c434b46d/fmicb-16-1560441-g0001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f690/12370734/ab053ba609c8/fmicb-16-1560441-g0002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f690/12370734/048127c88c1f/fmicb-16-1560441-g0003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f690/12370734/222cf1abb69d/fmicb-16-1560441-g0004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f690/12370734/d1e94bdff579/fmicb-16-1560441-g0005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f690/12370734/00b22f3bf2d6/fmicb-16-1560441-g0006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f690/12370734/2567c434b46d/fmicb-16-1560441-g0001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f690/12370734/ab053ba609c8/fmicb-16-1560441-g0002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f690/12370734/048127c88c1f/fmicb-16-1560441-g0003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f690/12370734/222cf1abb69d/fmicb-16-1560441-g0004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f690/12370734/d1e94bdff579/fmicb-16-1560441-g0005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f690/12370734/00b22f3bf2d6/fmicb-16-1560441-g0006.jpg

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