暴露于粉尘的大鼠的肠道微生物组和代谢组学特征

IF 1.6 4区 医学 Q4 BIOCHEMICAL RESEARCH METHODS
Xi Shen, Miaomiao Wang, Shasha Pei, Shuyu Xiao, Kun Xiao, Jinlong Li, Xiaoming Li, Qingan Xia, Heliang Liu, Fuhai Shen
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引用次数: 0

摘要

背景:有限的矽肺治疗需要进一步研究尘肺病的特征和病理生理。本研究采用代谢组学研究代谢物的变化和鉴定生物标志物,以了解尘肺发病机制。方法:选取健康SPF雄性SD大鼠18只,分为对照组、煤尘组和二氧化硅组,通过肠道菌群的视角探讨尘肺发病机制。暴露于粉尘后,分析代谢物的变化,以确定代谢标志物和途径。我们评估了肠道菌群与矽肺的关系,旨在提供早期诊断证据。大鼠分别暴露于煤尘、二氧化硅或无菌生理盐水中8周,之后采集血液、肺组织和粪便。评估肺部病理,检测炎症因子(IL-6、IL-11)。采用16S rDNA测序和UHPLC-QTOFMS代谢组学分析肠道菌群和粪便代谢物。结果:与对照组相比,暴露于粉尘8周后,暴露于二氧化硅的大鼠体重明显减轻,血清IL-6和IL-11水平明显升高(P < 0.05)。肺组织病理学显示对照组肺泡结构正常,而硅组大鼠肺损伤,炎症加剧,硅结节形成。煤尘组大鼠肺组织出现成纤维细胞聚集改变。α多样性分析显示,煤粉组的Shannon指数降低,Simpson指数升高,二氧化硅组的Simpson指数降低,表明肠道菌群发生了改变。β多样性分析证实了粉尘暴露组和对照组之间肠道微生物群的显著差异。代谢组学鉴定出大鼠粪便中有11种差异代谢物,符合Fold change >2, VIP > 1标准,P < 0.05,表明暴露后代谢发生变化。结论:粉尘暴露会破坏肠道菌群和代谢状态,在煤尘组和二氧化硅组中都发现了潜在的代谢标志物,暗示煤尘暴露中果糖和甘露糖代谢,二氧化硅暴露中鞘脂代谢。本研究为尘肺病的发病机制和潜在的早期诊断生物标志物提供了新的见解。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
The Gut Microbiome and Metabolomics Profiles of Dust-exposed Rats.

Background: Limited treatments for silicosis necessitate further study of pneumoconiosis characteristics and pathophysiology. This study employs metabolomics to investigate metabolite changes and identify biomarkers for understanding pneumoconiosis pathogenesis.

Methods: We explored pneumoconiosis pathogenesis through the lens of intestinal flora, using 18 healthy SPF male SD rats divided into three groups: control, coal dust, and silica. After dust exposure, metabolite changes were analyzed to identify metabolic markers and pathways. We assessed the relationship between intestinal flora and silicosis, aiming to provide early diagnostic evidence. Rats were exposed to coal dust, silica, or sterile saline for 8 weeks, after which blood, lung tissue, and feces were collected. Lung pathology was assessed, and inflammatory factors (IL-6, IL-11) were measured. 16S rDNA sequencing and UHPLC-QTOFMS metabolomics were used to analyze intestinal flora and fecal metabolites.

Results: After 8 weeks of dust exposure, silica-exposed rats showed significantly reduced weight and elevated serum IL-6 and IL-11 levels compared to controls (P < 0.05). Lung tissue pathology revealed normal alveolar structure in controls, whereas silica group rats exhibited lung damage, intensified inflammation, and silicon nodule formation. Coal dust group rats showed lung tissue changes with fibroblast aggregation. α diversity analysis showed a decreased Shannon index and increased Simpson index in the coal dust group, and a decreased Simpson index in the silica group, suggesting altered intestinal flora. β diversity analysis confirmed significant differences in gut microbiota between dust-exposed groups and controls. Metabolomics identified 11 differential metabolites in rat feces, meeting criteria of Fold change > 2, VIP > 1, and P < 0.05, indicating metabolic changes post-exposure.

Conclusion: Dust exposure disrupts intestinal flora and metabolic state, with potential metabolic markers identified in both coal dust and silica groups, implicating fructose and mannose metabolism in coal dust exposure and sphingolipid metabolism in silica exposure. This study provides new insights into the pathogenesis of pneumoconiosis and potential biomarkers for early diagnosis.

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来源期刊
CiteScore
3.10
自引率
5.60%
发文量
327
审稿时长
7.5 months
期刊介绍: Combinatorial Chemistry & High Throughput Screening (CCHTS) publishes full length original research articles and reviews/mini-reviews dealing with various topics related to chemical biology (High Throughput Screening, Combinatorial Chemistry, Chemoinformatics, Laboratory Automation and Compound management) in advancing drug discovery research. Original research articles and reviews in the following areas are of special interest to the readers of this journal: Target identification and validation Assay design, development, miniaturization and comparison High throughput/high content/in silico screening and associated technologies Label-free detection technologies and applications Stem cell technologies Biomarkers ADMET/PK/PD methodologies and screening Probe discovery and development, hit to lead optimization Combinatorial chemistry (e.g. small molecules, peptide, nucleic acid or phage display libraries) Chemical library design and chemical diversity Chemo/bio-informatics, data mining Compound management Pharmacognosy Natural Products Research (Chemistry, Biology and Pharmacology of Natural Products) Natural Product Analytical Studies Bipharmaceutical studies of Natural products Drug repurposing Data management and statistical analysis Laboratory automation, robotics, microfluidics, signal detection technologies Current & Future Institutional Research Profile Technology transfer, legal and licensing issues Patents.
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