粪菌移植影响砷染毒子代大鼠神经行为及肠道菌群的初步研究  

Preliminary study on the effect of fecal microbiota transplantation on neurobehavior and gut microbiota of offspring rats exposed to arsenic

作　　者：赵倩[1] 郝岩 杨晓倩 阎小艳 仇玉兰[1] Zhao Qian;Hao Yan;Yang Xiaoqian;Yan Xiaoyan;Qiu Yulan(Department of Health Toxicology,School of Public Health,Shanxi Medical University,Taiyuan 030001,China)

机构地区：[1]山西医科大学公共卫生学院卫生毒理学教研室,太原030001

出　　处：《中华劳动卫生职业病杂志》2023年第1期14-20,共7页Chinese Journal of Industrial Hygiene and Occupational Diseases

基　　金：国家自然科学基金青年项目(82103961);国家自然科学基金面上项目(81773405);山西省自由探索类青年科学研究项目(20210302124297)。

摘　　要：目的探讨粪菌移植(FMT)对砷染毒子代大鼠神经行为及肠道菌群的影响。方法于2021年4月,选择36只8周龄SPF级SD大鼠,根据大鼠体重按随机区组法将其分为对照组、砷染毒组(As组)、砷+生理盐水组(As+NaCl组)和As+FMT组,各组中雌鼠6只、雄鼠3只;选取对照组大鼠粪便作为粪菌液供体。大鼠饮用含75 mg/L亚砷酸钠的自来水1周后进行合笼,至子代大鼠出生终止砷暴露。雌鼠出现阴栓后在神经发育致畸窗口期进行粪菌液灌胃,灌胃体积为1 ml/100 g,间隔2 d 1次,共3次。子代大鼠断乳后每周记录体重变化,出生第6周后,采用水迷宫试验检测大鼠的学习记忆能力,旷场试验观察大鼠自主探索行为与紧张度的神经行为表现;采用16S rDNA测序技术检测As组和As+FMT组大鼠粪便样本中菌群多样性变化情况。结果与对照组比较,As组大鼠在目标象限的游泳距离比和停留时间比,以及穿越平台的次数均明显下降,且大鼠在中心区的运动路程、进入次数和跨格数均明显降低(P<0.05);与As组比较,As+FMT组大鼠在目标象限的停留时间比,在中心区的运动路程和进入次数均明显升高(P<0.05)。肠道菌群多样性分析显示,As+FMT组大鼠粪便菌群在门水平上拟杆菌门相对丰度高于As组(68.34%比60.55%),厚壁菌门相对丰度低于As组(28.02%比33.48%);在属水平上,As+FMT组普氏菌相对丰度明显高于As组,成为优势菌属(42.08%比21.78%)。此外,对比As组,As+FMT组大鼠粪便菌群中有22个上升的菌属,21个下降的菌属(P<0.05)。LEfSe法分析结果显示,As+FMT组差异菌属中的优势菌为普氏菌和UCG005,其相对丰度明显高于As组(P<0.05)。结论FMT可能缓解砷染毒子代大鼠的学习记忆能力受损和焦虑样行为,改善紊乱肠道菌群。Objective To explore the effects of fecal microbiota transplantation(FMT)on neurobehavior and gut microbiota of arsenic-exposed offspring rats.Methods In April 2021,Thirty-six SPF SD rats aged 8 weeks were seleted,rats were ranked by weight and divided into four groups according to randomized block design,namely control group,arsenic exposure group(As group),arsenic+normal saline group(As+NaCl group)and As+FMT group,6 females and 3 males in each group.Fecal microbiota fluid were provided by feces of rats in control group.Rats drank tap water containing 75 mg/L sodium arsenite for one week and then were caged together.The arsenic exposure was terminated until the pups were born.Female rats with vaginal plug were treated with fecal microbiota fluid via gavage during neurodevelopmental teratogenic window period.The volume of gavage was 1 ml/100 g with once every two days,for a total of three times.Weight alterations of offspring rats were recorded every week after weaning,and when offspring rats grew up for 6 weeks,Morris test and open field experiment was used to observe learning and memory abilities,as well as neurobehavioral performance of autonomous exploration and tension,respectively.16S rDNA sequencing technology was used to detect microbiota diversities in fecal samples of rats in As group and As+FMT group.Results Compared with the control group,the ratio of swimming distance and staying time in the target quadrant and the times of crossing the platform of rats in As group decreased significantly,and the motor distance,times entering central zone and the number of grid crossing of rats decreased significantly(P<0.05).Compared with As group,the ratio of swimming distance in target quadrant,the motor distance in central zone and times entering central zone of rats in As+FMT group were evidently increased(P<0.05).The analysis of fecal microbiota diversities showed that,at the phyla level,the relative abundance of Bacteroidetes in feces of rats in As+FMT group was higher than that in As group(68.34%vs 60.55%),wh

关 键 词：大鼠 子代 砷 粪菌移植 神经行为 肠道菌群 

分 类 号：R114[医药卫生—卫生毒理学]