Inhaled diesel exhaust particles result in microbiome-related systemic inflammation and altered cardiovascular disease biomarkers in C57Bl/6 male mice.
Inhaled diesel exhaust particles result in microbiome-related systemic inflammation and altered cardiovascular disease biomarkers in C57Bl/6 male mice.
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吸入柴油机尾气颗粒会导致 C57Bl/6 雄性小鼠与微生物组相关的全身炎症并改变心血管疾病生物标志物。
DOI：
10.1186/s12989-022-00452-3
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发表时间：
2022-02-09
影响因子：
10
通讯作者：
Lund AK
中科院分区：
文献类型：
--
作者：
Phillippi DT;Daniel S;Pusadkar V;Youngblood VL;Nguyen KN;Azad RK;McFarlin BK;Lund AK
肠道微生物群在宿主体内平衡中发挥着至关重要的作用，并与炎症和心血管疾病 (CVD) 风险相关。接触颗粒物 (PM) 是一种已知的炎症和心血管疾病介质，据报道会促进菌群失调和肠道完整性下降。然而，吸入交通产生的 PM 对肠道微生物群的作用及其相应的系统影响尚不清楚。因此，我们研究了这样的假设：暴露于吸入柴油机尾气颗粒 (DEP) 会改变肠道微生物组并促进微生物相关炎症和 CVD 生物标志物。采用低脂（LF，10% 脂肪）或高脂（HF，45% 脂肪）饮食的 4-6 周龄雄性 C57Bl/6 小鼠通过口咽抽吸暴露于悬浮在 35 μl 盐水中的 35 μg DEP 或仅盐水 (CON)，每周 2 次，持续 30 天。为了确定益生菌是否可以预防饮食或 DEP 暴露介导的肠道微生物组或全身结果的改变，在整个研究过程中，对 HF 饮食的一部分动物口服 0.3 g/天（~ 7.5 × 108 CFU/天）的 Winclove Ecologic® Barrier 益生菌。我们的结果表明，吸入 DEP 暴露会改变肠道微生物特征，包括减少放线菌和扩大疣微菌和变形菌。我们在 DEP 暴露和/或 HF 饮食小鼠中观察到循环 LPS 增加、循环细胞因子（IL-1α、IL-3、IL-13、IL-15、G-CSF、LIF、MIP-2 和 TNF-α）和 CVD 生物标志物（siCAM、PAI-1、sP-选择素、血栓调节蛋白和 PECAM）改变。此外，益生菌减弱了在 DEP 暴露和 HF 饮食小鼠中观察到的放线菌减少和变形菌扩张。益生菌可减轻 DEP 暴露和/或 HF 饮食中的循环细胞因子（IL-3、IL-13、G-CSF、RANTES 和 TNF-α）和 CVD 生物标志物（siCAM、PAI-1、sP-选择素、血栓调节蛋白和 PECAM）。这项研究的主要发现是，吸入 DEP 暴露会改变小肠微生物特征，而这些微生物特征在全身炎症和早期 CVD 生物标志物中发挥作用。本研究中的益生菌治疗对于了解吸入 DEP 对微生物组以及相关全身炎症和 CVD 生物标志物的作用至关重要。在线版本包含可在 10.1186/s12989-022-00452-3 获取的补充材料。
The gut microbiota plays a vital role in host homeostasis and is associated with inflammation and cardiovascular disease (CVD) risk. Exposure to particulate matter (PM) is a known mediator of inflammation and CVD and is reported to promote dysbiosis and decreased intestinal integrity. However, the role of inhaled traffic-generated PM on the gut microbiome and its corresponding systemic effects are not well-characterized. Thus, we investigated the hypothesis that exposure to inhaled diesel exhaust particles (DEP) alters the gut microbiome and promotes microbial-related inflammation and CVD biomarkers. 4–6-week-old male C57Bl/6 mice on either a low-fat (LF, 10% fat) or high-fat (HF, 45% fat) diet were exposed via oropharyngeal aspiration to 35 μg DEP suspended in 35 μl saline or saline only (CON) 2x/week for 30 days. To determine whether probiotics could prevent diet or DEP exposure mediated alterations in the gut microbiome or systemic outcomes, a subset of animals on the HF diet were treated orally with 0.3 g/day (~ 7.5 × 108 CFU/day) of Winclove Ecologic® Barrier probiotics throughout the study. Our results show that inhaled DEP exposure alters gut microbial profiles, including reducing Actinobacteria and expanding Verrucomicrobia and Proteobacteria. We observed increased circulating LPS, altered circulating cytokines (IL-1α, IL-3, IL-13, IL-15, G-CSF, LIF, MIP-2, and TNF-α), and CVD biomarkers (siCAM, PAI-1, sP-Selectin, thrombomodulin, and PECAM) in DEP-exposed and/or HF diet mice. Furthermore, probiotics attenuated the observed reduction of Actinobacteria and expansion of Proteobacteria in DEP-exposed and HF-diet mice. Probiotics mitigated circulating cytokines (IL-3, IL-13, G-CSF, RANTES, and TNF- α) and CVD biomarkers (siCAM, PAI-1, sP-Selectin, thrombomodulin, and PECAM) in respect to DEP-exposure and/or HF diet. Key findings of this study are that inhaled DEP exposure alters small intestinal microbial profiles that play a role in systemic inflammation and early CVD biomarkers. Probiotic treatment in this study was fundamental in understanding the role of inhaled DEP on the microbiome and related systemic inflammatory and CVD biomarkers. The online version contains supplementary material available at 10.1186/s12989-022-00452-3.
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影响因子：
4.6
作者：
Gulhane M;Murray L;Lourie R;Tong H;Sheng YH;Wang R;Kang A;Schreiber V;Wong KY;Magor G;Denman S;Begun J;Florin TH;Perkins A;Cuív PÓ;McGuckin MA;Hasnain SZ
通讯作者：
Hasnain SZ
影响因子：
10
作者：
Daniel S;Phillippi D;Schneider LJ;Nguyen KN;Mirpuri J;Lund AK
通讯作者：
Lund AK
影响因子：
6.8
作者：
Daniel S;Pusadkar V;McDonald J;Mirpuri J;Azad RK;Goven A;Lund AK
通讯作者：
Lund AK
影响因子：
7.3
作者：
Cristofori F;Dargenio VN;Dargenio C;Miniello VL;Barone M;Francavilla R
通讯作者：
Francavilla R
影响因子：
12.2
作者：
Ettinger G;MacDonald K;Reid G;Burton JP
通讯作者：
Burton JP