Department of Biological Sciences, Advanced Environmental Research Institute, University of North Texas, EESAT - 215, 1704 W. Mulberry, Denton, TX, 76203, USA.
BioDiscovery Institute, Department of Biological Sciences, University of North Texas, Denton, TX, 76203, USA.
Part Fibre Toxicol. 2022 Feb 9;19(1):10. doi: 10.1186/s12989-022-00452-3.
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 × 10 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.
肠道微生物群在宿主稳态中起着至关重要的作用，与炎症和心血管疾病 (CVD) 风险有关。颗粒物 (PM) 的暴露是炎症和 CVD 风险的已知介质，据报道可促进肠道菌群失调和肠道完整性降低。然而，吸入交通产生的 PM 对肠道微生物组及其相应的全身影响的作用尚不清楚。因此，我们假设暴露于吸入的柴油废气颗粒 (DEP) 会改变肠道微生物组，并促进与微生物相关的炎症和 CVD 生物标志物。4-6 周龄的雄性 C57Bl/6 小鼠分别在低脂 (LF，10%脂肪) 或高脂 (HF，45%脂肪) 饮食下，通过口咽部抽吸暴露于 35μg DEP 悬浮在 35μl 盐水中或仅生理盐水 (CON) 中，每周 2 次，共 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，一部分高脂饮食的动物在整个研究过程中每天口服 0.3g (~7.5×10 CFU/天) 的 Winclove Ecologic® Barrier 益生菌。
我们的结果表明，吸入 DEP 暴露改变了肠道微生物群的特征，包括减少放线菌和扩大厚壁菌门和变形菌门。我们观察到循环 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-Selectin、血栓调节蛋白和 PECAM) 在 DEP 暴露和/或 HF 饮食的小鼠中发生改变。此外，益生菌减轻了 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。益生菌减轻了循环细胞因子 (IL-3、IL-13、G-CSF、RANTES 和 TNF-α) 和 CVD 生物标志物 (siCAM、PAI-1、sP-Selectin、血栓调节蛋白和 PECAM) 与 DEP 暴露和/或 HF 饮食有关。
这项研究的主要发现是，吸入 DEP 暴露改变了小肠微生物群，这些微生物群在全身炎症和早期 CVD 生物标志物中发挥作用。在这项研究中，益生菌治疗对于了解吸入 DEP 对微生物组及其相关全身炎症和 CVD 生物标志物的作用至关重要。
