丁酸梭菌缓解DNCB诱导小鼠特应性皮炎的作用机制研究  

Mechanism of Clostridium butyricum in alleviating DNCB-induced atopic dermatitis in mice

作　　者：王梓宁 何爽 张杭 张稼瑞 李蓉 Wang Zining;He Shuang;Zhang Hang;Zhang Jiarui;Li Rong(School of Medicine and Pharmacy,Ocean University of China,Qingdao 266000,China;Qingdao Medical College,Qingdao University,Qingdao 266000,China;Department of Pharmacy,Women and Children's Hospital Affiliated to Qingdao University,Qingdao 266000,China)

机构地区：[1]中国海洋大学医药学院,青岛266000 [2]青岛大学青岛医学院,青岛266000 [3]青岛大学附属妇女儿童医院药学部,青岛266000

出　　处：《中华微生物学和免疫学杂志》2025年第2期115-124,共10页Chinese Journal of Microbiology and Immunology

摘　　要：目的从免疫细胞、肠道菌群以及肠道菌群代谢物短链脂肪酸(short-chain fatty acids,SCFAs)这3个方面揭示丁酸梭菌缓解特应性皮炎(atopic dermatitis,AD)的可能机制,为临床上益生菌辅助治疗AD提供理论参考。方法采用BALB/c小鼠建立2,4-二硝基氯苯(2,4-dinitrochlorobenzene,DNCB)诱导AD模型,设置对照组、AD组以及丁酸梭菌干预组,每组20只。记录3组小鼠皮炎及搔抓评分、皮损部位皮肤病理学结果及肥大细胞浸润情况,以及血清中Th1/Th2、Th17/Treg相关细胞因子和IgE水平;16S rRNA测序检测小鼠肠道菌群;气相色谱质谱法检测小鼠粪便中SCFAs含量;Spearman相关性分析探究Th1/Th2和Th17/Treg相关细胞因子水平、肠道菌群组成、SCFAs含量之间的相关性。多组间比较采用单因素方差分析及Turkey事后检验校正。结果丁酸梭菌干预可以下调AD小鼠各项炎症指标并减轻病理变化,升高血清中IFN-γ(P<0.05)和IL-10水平(P<0.01),降低IL-4、IL-17、IgE水平(P<0.01),维持Th1/Th2(P<0.01)和Th17/Treg平衡(P<0.001);改善肠道菌群失调,降低Prevotellaceae_UCG-001等条件致病菌的丰度(P<0.01),提高Lachnospiraceae_NK4A136_group、norank_f_Oscillospiraceae等有益菌的丰度(P<0.05),增强SCFAs的产生(P<0.05)。相关性分析显示,过敏相关免疫细胞因子与肠道菌群组成及SCFAs的含量显著相关。结论丁酸梭菌可能通过下调肠道有害菌丰度和增加肠道有益菌丰度来调节菌群-SCFAs信号反应,从而提高SCFAs水平,降低促炎细胞因子数量,维持机体Th1/Th2、Th17/Treg平衡,进而缓解过敏性疾病。Objective To elucidate the mechanism by which Clostridium butyricum alleviates atopic dermatitis(AD)from three aspects:immune cells,gut microbiota,and the metabolites of gut microbiota,short-chain fatty acids(SCFAs),and provide a theoretical reference for clinical probiotic-assisted treatment of AD.MethodsA model of 2,4-dinitrochlorobenzene(DNCB)-induced AD was established using BALB/c mice.Three groups including control group,AD group,and Clostridium butyricum intervention group were set up with 20 mice in each group.The dermatitis score,scratching score,pathological conditions and mast cell infiltration at the lesion site,and the levels of cytokines related to Th1/Th2 and Th17/Treg as well as IgE levels in serum samples were analyzed.Gut microbiota was detected by 16S rRNA gene sequencing.The contents of SCFAs in mouse fecal samples were detected by gas chromatography-mass spectrometry.Spearman correlation analysis was performed to investigate the correlation between the cytokines related to Th1/Th2 and Th17/Treg,gut microbiota,and SCFAs.Comparisons between groups were performed using one-way analysis of variance with Turkey post hoc test correction.Results Clostridium butyricum intervention down-regulated various inflammatory indexes and alleviated pathological changes in AD mice,elevated the levels of IFN-γ(P<0.05)and IL-10(P<0.01),reduced the levels of IL-4,IL-17 and IgE(P<0.01),and maintained the balance of Th1/Th2(P<0.01)and Th17/Treg(P<0.001).Besides,the intervention improved intestinal dysbiosis by decreasing the abundance of conditionally pathogenic bacteria such as Prevotellaceae_UCG-001(P<0.01)and increasing the abundance of beneficial bacteria such as Lachnospiraceae_NK4A136_group and norank_f_Oscillospiraceae(P<0.05),and enhanced the production of SCFAs(P<0.05).Correlation analysis showed that allergy-associated immune cytokines were strongly correlated with the composition of gut microbiota and the content of SCFAs.Conclusions Clostridium butyricum may regulate the microbiota-SCFAs signaling respo

关 键 词：特应性皮炎 肠道菌群 丁酸梭菌 短链脂肪酸 TH1/TH2 TH17/TREG 

分 类 号：R28[医药卫生—中药学]