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邻苯二甲酸二丁酯暴露小鼠肠道微生物群群落结构改变及相关免疫系统变化

Altered gut microbiota community structure and correlated immune system changes in dibutyl phthalate exposed mice.

作者信息

Almamoun Radwa, Pierozan Paula, Manoharan Lokeshwaran, Karlsson Oskar

机构信息

Science for Life Laboratory, Department of Environmental Science, Stockholm University, 11418, Stockholm, Sweden.

National Bioinformatics Infrastructure Sweden (NBIS), SciLifeLab, Department of Laboratory Medicine, Lund University, Lund, Sweden.

出版信息

Ecotoxicol Environ Saf. 2023 Aug 5;262:115321. doi: 10.1016/j.ecoenv.2023.115321.

Abstract

Di-n-butyl phthalate (DBP) is a ubiquitous environmental contaminant linked with various adverse health effects, including immune system dysfunction. Gut microbial dysbiosis can contribute to a wide range of pathogenesis, particularly immune disease. Here, we investigated the impact of DBP on the gut microbiome and examined correlations with immune system changes after five weeks oral exposure (10 or 100 mg/kg/day) in adult male mice. The fecal microbiome composition was characterized using 16S rRNA sequencing. DBP-treated mice displayed a significantly distinct microbial community composition, indicated by Bray-Curtis distance. Numerous amplicon sequence variants (ASVs) at the genus level were altered. Compared to the vehicle control group, the 10 mg/kg/day DBP group had 63 more abundant and 65 less abundant ASVs, while 60 ASVs were increased and 76 ASVs were decreased in the 100 mg/kg/day DBP group. Both DBP treatment groups showed higher abundances of ASVs assigned to Desulfovibrio (Proteobacteria phylum) and Enterorhabdus genera, while ASVs belonging to Parabacteroides, Lachnospiraceae UCG-006 and Lachnoclostridium were less common compared to the control group. Interestingly, an ASV belonging to Rumniniclostridium 6, which was less abundant in DBP-treated mice, demonstrated a negative correlation with the increased number of non-classical monocytes observed in the blood of DBP-treated animals. In addition, an ASV from Lachnospiraceae UCG-001, which was more abundant in the DBP-treated animals, showed a positive correlation with the non-classical monocyte increase. This study shows that DBP exposure greatly modifies the gut bacterial microbiome and indicates a potential contribution of microbial dysbiosis to DBP-induced immune system impairment, illustrating the importance of investigating how interactions between exposome components can affect health.

摘要

邻苯二甲酸二正丁酯(DBP)是一种普遍存在的环境污染物,与包括免疫系统功能障碍在内的各种不良健康影响有关。肠道微生物群失调可导致多种发病机制,尤其是免疫疾病。在此,我们研究了DBP对肠道微生物群的影响,并在成年雄性小鼠口服暴露五周(10或100毫克/千克/天)后,检查了其与免疫系统变化的相关性。使用16S rRNA测序对粪便微生物群组成进行了表征。经DBP处理的小鼠表现出明显不同的微生物群落组成,通过Bray-Curtis距离表示。属水平上的许多扩增子序列变体(ASV)发生了改变。与载体对照组相比,10毫克/千克/天DBP组的ASV丰度增加了63个,减少了65个,而100毫克/千克/天DBP组的ASV增加了60个,减少了76个。两个DBP处理组中,属于脱硫弧菌属(变形菌门)和肠栖菌属的ASV丰度较高,而与对照组相比,属于副拟杆菌属、毛螺菌科UCG-006和瘤胃梭菌属的ASV较少见。有趣的是,在经DBP处理的小鼠中丰度较低的一种属于瘤胃梭菌6的ASV,与在经DBP处理动物血液中观察到的非经典单核细胞数量增加呈负相关。此外,在经DBP处理的动物中丰度较高的来自毛螺菌科UCG-001的一种ASV,与非经典单核细胞增加呈正相关。这项研究表明,DBP暴露极大地改变了肠道细菌微生物群,并表明微生物失调可能对DBP诱导的免疫系统损害有潜在影响,说明了研究暴露组各成分之间的相互作用如何影响健康的重要性。

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