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[粪菌移植对砷暴露子代大鼠神经行为及肠道菌群影响的初步研究]

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

作者信息

Zhao Q, Hao Y, Yang X Q, Yan X Y, Qiu Y L

机构信息

Department of Health Toxicology, School of Public Health, Shanxi Medical University, Taiyuan 030001, China.

出版信息

Zhonghua Lao Dong Wei Sheng Zhi Ye Bing Za Zhi. 2023 Jan 20;41(1):14-20. doi: 10.3760/cma.j.cn121094-20220311-00125.

DOI:10.3760/cma.j.cn121094-20220311-00125
PMID:36725289
Abstract

To explore the effects of fecal microbiota transplantation (FMT) on neurobehavior and gut microbiota of arsenic-exposed offspring rats. 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. 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 (<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 (<0.05) . The analysis of fecal microbiota diversities showed that, at the phyla level, the relative abundance of in feces of rats in As+FMT group was higher than that in As group (68.34% 60.55%) , while the relative abundance of was lower than that in As group (28.02% 33.48%) . At the genus level, the relative abundance of in As+FMT group was significantly higher than that in As group, becoming the dominant genus (42.08% 21.78%) . Additionally, compared with As group, a total of 22 genus were increased with 21 decreased genus in As+FMT group (<0.05) . LEfSe analysis showed that dominant genuses in As+FMT group were and , and their relative abundance was significantly higher than that of As group (<0.05) . FMT may alleviate the impaired learning and memory ability and anxiety like behavior of the offspring rats exposed to arsenic, and improve the disrupted gut microbiota.

摘要

探讨粪菌移植(FMT)对砷暴露子代大鼠神经行为及肠道菌群的影响。2021年4月,选取36只8周龄的SPF级SD大鼠,按体重排序,根据随机区组设计分为四组,即对照组、砷暴露组(As组)、砷+生理盐水组(As+NaCl组)和As+FMT组,每组6只雌性和3只雄性。对照组大鼠粪便提供粪菌液。大鼠饮用含75 mg/L亚砷酸钠的自来水一周后合笼饲养。砷暴露持续至幼崽出生。有阴栓的雌性大鼠在神经发育致畸窗口期经口灌胃给予粪菌液。灌胃量为1 ml/100 g,每两天一次,共三次。断奶后每周记录子代大鼠体重变化,子代大鼠生长至6周龄时,分别采用Morris试验和旷场实验观察学习记忆能力以及自主探索和紧张的神经行为表现。采用16S rDNA测序技术检测As组和As+FMT组大鼠粪便样本中的菌群多样性。与对照组相比,As组大鼠在目标象限的游泳距离和停留时间比例以及穿越平台次数显著降低,运动距离、进入中央区域次数和穿越格数显著减少(<0.05)。与As组相比,As+FMT组大鼠在目标象限的游泳距离比例、中央区域的运动距离和进入中央区域次数明显增加(<0.05)。粪便菌群多样性分析显示,在门水平上,As+FMT组大鼠粪便中 的相对丰度高于As组(68.34% 对60.55%),而 的相对丰度低于As组(28.02% 对33.48%)。在属水平上,As+FMT组中 的相对丰度显著高于As组,成为优势菌属(42.08% 对21.78%)。此外,与As组相比,As+FMT组共有22个属增加,21个属减少(<0.05)。LEfSe分析显示,As+FMT组的优势菌属为 和 ,其相对丰度显著高于As组(<0.05)。粪菌移植可能减轻砷暴露子代大鼠受损的学习记忆能力和类焦虑行为,并改善肠道菌群紊乱。

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