凝结芽孢杆菌-乳果糖合生元对DSS诱导的溃疡性结肠炎小鼠肠道健康的影响  

Effect of synbiotic containing Bacillus coagulans and lactulose on gut health in mice with DSS-induced ulcerative colitis

作　　者：刘日亮 乔羽 黄桂青 钱薇 熊佳利 王新宇 郑卫江[1] 姚文[1] LIU Riliang;QIAO Yu;HUANG Guiqing;QIAN Wei;XIONG Jiali;WANG Xinyu;ZHENG Weijiang;YAO Wen(Jiangsu Key Laboratory of Gastrointestinal Nutrition and Animal Health,Laboratory of Gastrointestinal Microbiology,Nanjing Agricultural University,Nanjing 210095,Jiangsu,China)

机构地区：[1]南京农业大学消化道微生物实验室,江苏省消化道营养与动物健康重点实验室,江苏南京210095

出　　处：《微生物学报》2022年第3期869-881,共13页Acta Microbiologica Sinica

基　　金：国家级大学生创新创业训练计划(202010307025Z)。

摘　　要：【目的】旨在探究凝结芽孢杆菌-乳果糖合生元对葡聚糖硫酸钠(dextransodiumsulfate,DSS)诱导的溃疡性结肠炎小鼠临床体征、肠道形态和肠道菌群结构的影响。【方法】选取24只初始体重为(22.96±1.87) g的7周龄雄性C57/BL6小鼠,随机分为4组,每组6只,即CON组、DSS组(连续5 d饮用2.5%DSS水)、SYN-P组(合生元预防组,造模前7 d每日灌胃1次合生元)和SYN-T组(合生元治疗组,造模后7 d每日灌胃1次合生元)。适应期7 d,试验期19 d,随后实施安乐死采样。【结果】第10天DSS造模后,除CON组外其余3组小鼠体重开始下降,其中DSS组小鼠体重下降速度最快且疾病活动指数(DAI)最高;第14天停止饮用DSS后,SYN-P和SYN-T组体重逐渐恢复正常,而DSS组未能恢复。与CON组相比,DSS组小鼠结肠长度显著降低(P<0.05),单位体重的肝脏和脾脏重量显著增加(P<0.05),SYN-T组小鼠单位体重的肝脏重量显著增加(P<0.05)。组织形态学分析表明:CON组结肠绒毛高度显著高于DSS和SYN-P组(P<0.05),DSS组结肠隐窝深度显著高于其他三组(P<0.05),DSS组结肠绒毛隐窝比显著低于SYN-P和SYN-T组(P<0.05)。盲肠菌群分析表明:菌群多样性指数显著改变(ACE、Chao1、Shannon和Anova,P<0.05);门水平上,相较于DSS组,SYNP组Desulfobacterota和脱铁杆菌门(Deferribacteres)相对丰度显著下降(P<0.05),SYNT组脱铁杆菌门(Deferribacteres)相对丰度显著下降(P<0.05);属水平上,肠球菌属(Enterococcus)等13个优势菌属相对丰度发生改变。PICRUSt分析表明:相较于CON和DSS组,SYN-P和SYN-T组碳水化合物代谢KEGG通路显著上调(P<0.05);另外果糖和甘露糖代谢等11条3级代谢通路受到影响。【结论】乳果糖和凝结芽孢杆菌合生元通过预防和治疗两种方式可缓解DSS所诱导的溃疡性结肠炎小鼠相关临床症状,改善肠道组织形态,减少肠道内引发炎症反应的Desulfobacterota和脱铁杆菌门(Deferribacteres)相对丰度。[Objective] To investigate the effect of synbiotic containing Bacillus coagulans and lactulose on clinical symptoms, intestinal morphology and microbiota in mice with dextran sodium sulfate(DSS)-induced ulcerative colitis. [Methods] A total of 24 7-week-old male C57/BL6 mice with initial body weight of(22.96±1.87) g were randomized into 4 groups(6 in each): control group(CON),DSS group(2.5% DSS in water for 5 days), SYN-P group(gastric gavage of oral synbiotic once a day for 7 days before DSS administration), and SYN-T group(gastric gavage of oral synbiotic once a day for 7 days after DSS administration). After 7-day pre-feeding period and 19-day experimental period,the mice were euthanized and samples were collected. [Results] On the 10 th day in the experimental period, except CON group, mice began to lose weight, among which DSS group had the fastest weight loss and the highest disease activity index(DAI). After DSS treatment was terminated(14 th day), the body weight of SYN-P and SYN-T groups gradually returned to normal level, while that of DSS group did not. Compared with CON group, DSS group showed decrease in colon length(P<0.05) and increase in liver and spleen indexes(liver or spleen weight/body weight)(P<0.05), while SYN-T group demonstrated rise of liver index(P<0.05). As for the histomorphology, the height of colon villi in CON group was larger than that in DSS and SYN-P groups(P<0.05), and colonic crypt depth in DSS group was larger than that in the other three groups(P<0.05). The villus height-to-crypt depth ratio in DSS group was significantly smaller than that in SYN-P and SYN-T groups(P<0.05). As to the caecal microflora, the diversity indexes(ACE, Chao1, Shannon, and Anova) of microflora changed(P<0.05).At the phylum level, the relative abundance of Desulfobacterota and Deferribacteres in SYN-P group decreased(P<0.05) and that of Deferribacteres in SYN-T group reduced(P<0.05) compared with that in DSS group. At the genus level, the relative abundance of 13 dominant genera such as Enterococcus

关 键 词：凝结芽孢杆菌 乳果糖 DSS 肠道菌群 

分 类 号：R574.62[医药卫生—消化系统]