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转录组学变化和肠道免疫反应与长双歧杆菌BAA2573在改善葡聚糖硫酸钠诱导的结肠炎中的关联。

Association of alterations in transcriptomics and intestinal immune responses with Bifidobacterium longum BAA2573 in improving dextran sulfate sodium-induced colitis.

作者信息

Hao Wujuan, Gu Lan, Zhou Renmin, Huang Cuilan, Wang Xuyang, Liu Yanshan, Lin Qiong

机构信息

Department of Digestive, Affiliated Children's Hospital of Jiangnan University, Wuxi, Jiangsu, China.

Nanjing Medical University, Nanjing, Jiangsu, China.

出版信息

BMC Gastroenterol. 2025 Aug 1;25(1):551. doi: 10.1186/s12876-025-04116-2.

DOI:10.1186/s12876-025-04116-2
PMID:40750856
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12317558/
Abstract

BACKGROUND

Preliminary studies have demonstrated the potential of Bifidobacterium longum (B. longum) BAA2573 in alleviating dextran sulfate sodium (DSS)-induced colitis; however, the underlying mechanisms are still unclear.

OBJECTIVE

To investigate the intestinal immune responses and molecular changes upon B. Longum BAA2573 treatment.

METHODS

C57BL/6 J mice (6-8 weeks) were divided into three groups, control (CON), DSS, and B. longum BAA2573 intervention group (B + DSS). The B + DSS group was pretreated with B. longum BAA2573 for six days before induction with DSS. The body weight, stool characteristics, and disease activity index were recorded daily. After the 12-day intervention, the colonic tissues and serum from each group were collected for further analysis. Immunofluorescence assay was conducted to detect the infiltration of macrophages. qPCR and ELISA were used to analyze the expression of cytokines, RNA‑seq and subsequent qPCR were employed for the detection and validation of differentially expressed genes (DEGs), respectively. The crosstalk between DEGs and metabolites was also investigated.

RESULTS

B. longum BAA2573 treatment enhanced M2-macrophage infiltration in intestinal tissues. The levels of cytokine TNF-α and IL-6 in serum were decreased, while IL-10 and TGF-β1 were significantly increased after B. longum BAA2573 pretreatment. RNA-seq identified 202 DEGs between the DSS and B + DSS group, primarily enriched in the activation of the innate immune response and phagocytosis. B. longum BAA2573 may ameliorate immune disorders in colitis mice via regulating the PI3K-AKT and NK-κB signaling pathway. Four genes, Reg3b, Rnf213, Bcl2l15, and Chp2, were significantly associated with the therapeutic effect of B. longum BAA2573. Immune-related signaling were involved in the responses to metabolic disorders.

CONCLUSION

Pretreatment of B. longum BAA2573 demonstrated a promising anti-inflammatory effect in DSS-induced colitis. Supplementation of B. longum BAA2573 during UC development may represent a potential therapeutic approach by effectively maintaining intestinal immune and regulating inflammation-associated cytokines and pathways.

摘要

背景

初步研究已证明长双歧杆菌(B. longum)BAA2573在减轻葡聚糖硫酸钠(DSS)诱导的结肠炎方面具有潜力;然而,其潜在机制仍不清楚。

目的

研究长双歧杆菌BAA2573治疗后的肠道免疫反应和分子变化。

方法

将6-8周龄的C57BL/6 J小鼠分为三组,即对照组(CON)、DSS组和长双歧杆菌BAA2573干预组(B+DSS)。B+DSS组在DSS诱导前用长双歧杆菌BAA2573预处理6天。每天记录体重(body weight)、粪便特征和疾病活动指数。干预12天后,收集每组的结肠组织和血清进行进一步分析。进行免疫荧光分析以检测巨噬细胞的浸润情况。采用qPCR和ELISA分析细胞因子的表达,分别采用RNA测序(RNA-seq)和随后的qPCR检测和验证差异表达基因(DEGs)。还研究了差异表达基因与代谢物之间的相互作用。

结果

长双歧杆菌BAA2573治疗增强了肠道组织中M2巨噬细胞的浸润。长双歧杆菌BAA2573预处理后,血清中细胞因子TNF-α和IL-6水平降低,而IL-10和TGF-β1显著升高。RNA测序确定了DSS组和B+DSS组之间有202个差异表达基因,主要富集于先天免疫反应的激活和吞噬作用。长双歧杆菌BAA2573可能通过调节PI3K-AKT和NK-κB信号通路改善结肠炎小鼠的免疫紊乱。Reg3b、Rnf213、Bcl2l15和Chp2这四个基因与长双歧杆菌BAA2573的治疗效果显著相关。免疫相关信号参与了对代谢紊乱的反应。

结论

长双歧杆菌BAA2573预处理在DSS诱导的结肠炎中显示出有前景的抗炎作用。在溃疡性结肠炎(UC)发展过程中补充长双歧杆菌BAA2573可能是一种潜在的治疗方法,可通过有效维持肠道免疫和调节炎症相关细胞因子及信号通路来实现。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/05d8/12317558/5c7369c46264/12876_2025_4116_Fig7_HTML.jpg
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