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超细颗粒以性别特异性方式改变肥胖小鼠模型中的肠道微生物种群和代谢特征。

Ultrafine particles altered gut microbial population and metabolic profiles in a sex-specific manner in an obese mouse model.

机构信息

Department of Chemistry and Biochemistry, Miami University, Oxford, OH, 45056, USA.

Department of Biology, Miami University, Oxford, OH, 45056, USA.

出版信息

Sci Rep. 2021 Mar 25;11(1):6906. doi: 10.1038/s41598-021-85784-4.

DOI:10.1038/s41598-021-85784-4
PMID:33767227
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7994449/
Abstract

Emerging evidence has highlighted the connection between exposure to air pollution and the increased risk of obesity, metabolic syndrome, and comorbidities. Given the recent interest in studying the effects of ultrafine particle (UFP) on the health of obese individuals, this study examined the effects of gastrointestinal UFP exposure on gut microbial composition and metabolic function using an in vivo murine model of obesity in both sexes. UFPs generated from light-duty diesel engine combustion of petrodiesel (B0) and a petrodiesel/biodiesel fuel blend (80:20 v/v, B20) were administered orally. Multi-omics approaches, including liquid chromatography-mass spectrometry (LC-MS) based targeted metabolomics and 16S rRNA gene sequence analysis, semi-quantitatively compared the effects of 10-day UFP exposures on obese C57B6 mouse gut microbial population, changes in diversity and community function compared to a phosphate buffer solution (PBS) control group. Our results show that sex-specific differences in the gut microbial population in response to UFP exposure can be observed, as UFPs appear to have a differential impact on several bacterial families in males and females. Meanwhile, the alteration of seventy-five metabolites from the gut microbial metabolome varied significantly (ANOVA p < 0.05) across the PBS control, B0, and B20 groups. Multivariate analyses revealed that the fuel-type specific disruption to the microbial metabolome was observed in both sexes, with stronger disruptive effects found in females in comparison to male obese mice. Metabolic signatures of bacterial cellular oxidative stress, such as the decreased concentration of nucleotides and lipids and increased concentrations of carbohydrate, energy, and vitamin metabolites were detected. Furthermore, blood metabolites from the obese mice were differentially affected by the fuel types used to generate the UFPs (B0 vs. B20).

摘要

新出现的证据强调了暴露于空气污染与肥胖、代谢综合征和合并症风险增加之间的联系。鉴于最近人们对研究超细颗粒 (UFP) 对肥胖个体健康的影响产生了兴趣,本研究使用雄性和雌性肥胖动物体内模型,研究了胃肠道 UFP 暴露对肠道微生物组成和代谢功能的影响。使用轻负荷柴油发动机燃烧石油柴油 (B0) 和石油柴油/生物柴油燃料混合物 (80:20v/v,B20) 生成的 UFP 进行口服给药。采用基于液相色谱-质谱 (LC-MS) 的靶向代谢组学和 16S rRNA 基因序列分析等多组学方法,对 10 天 UFP 暴露对肥胖 C57B6 小鼠肠道微生物种群的影响进行了半定量比较,与磷酸盐缓冲溶液 (PBS) 对照组相比,多样性和群落功能的变化。我们的研究结果表明,UFP 暴露对肠道微生物种群的影响存在性别特异性差异,因为 UFP 似乎对雄性和雌性的几种细菌家族产生了不同的影响。同时,来自肠道微生物代谢组的七十五种代谢物的变化在 PBS 对照组、B0 组和 B20 组之间存在显著差异 (ANOVA p<0.05)。多元分析表明,在两性中都观察到了燃料类型对微生物代谢组的特异性破坏,与雄性肥胖小鼠相比,雌性的破坏作用更强。检测到细菌细胞氧化应激的代谢特征,如核苷酸和脂质浓度降低以及碳水化合物、能量和维生素代谢物浓度增加。此外,肥胖小鼠的血液代谢物受到用于生成 UFP 的燃料类型的影响而存在差异 (B0 与 B20)。

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