Ambient air pollution by particulate matters, including diesel exhaust particles (DEP), is a major cause of cardiovascular and metabolic mortality worldwide. The mechanisms by which DEP cause these adverse outcomes are not completely understood. Because the gut microbiota controls cardiovascular and metabolic health, we hypothesized that the fraction of inhaled DEP which reach the gut after mucociliary clearance and swallowing might induce gut dysbiosis and, in turn, contribute to aggravate or induce cardiovascular and metabolic diseases. Female ApoE−/− mice fed a Western diet, and wild-type (C57Bl/6) mice fed standard diet were gavaged with DEP (SRM2975) doses corresponding to mucociliary clearance from inhalation exposure (200 or 1000 ng/day, 3 times a week for 3 months; and 40, 200 or 1000 ng/day, 3 times a week for 6 months, respectively). No mortality, overt systemic or digestive toxicity was observed. A dose-dependent alteration of the gut microbiota was recorded in both strains. In ApoE−/−, β-diversity was modified by DEP, but no significant modification of the relative abundance of the phyla, families or genera was identified. In C57BL/6 mice, DEP reduced α-diversity (Shannon and Simpson indices), and modified β-diversity, including a reduction of the Proteobacteria and Patescibacteria phyla, and an increase of the Campylobacterota phylum. In both mouse models, perturbation of the gut microbiota composition was associated with a dose-dependent reduction of bacterial short chain fatty acids (butyrate and propionate) in cecal content. However, DEP ingestion did not aggravate (ApoE−/−), or induce (C57BL/6 mice) atherosclerotic plaques, and no metabolic alteration (glucose tolerance, resistance to insulin, or lipidemia) was recorded. We show here that oral exposure to DEP, at doses relevant for human health, changes the composition and function of the gut microbiota. These modifications were, however, not translated into ultimate atherosclerotic or metabolic outcomes.

中文翻译：

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柴油废气颗粒改变小鼠亚慢性口服后肠道微生物群的特征和功能

包括柴油机尾气颗粒 (DEP) 在内的颗粒物造成的环境空气污染是全球心血管和代谢死亡的主要原因。DEP 导致这些不良结果的机制尚不完全清楚。由于肠道微生物群控制心血管和代谢健康，我们假设在黏液纤毛清除和吞咽后到达肠道的吸入 DEP 部分可能会导致肠道菌群失调，进而导致加重或诱发心血管和代谢疾病。喂食西方饮食的雌性 ApoE-/- 小鼠和喂食标准饮食的野生型 (C57Bl/6) 小鼠灌胃 DEP (SRM2975) 剂量，对应于吸入暴露后的粘液纤毛清除率（200 或 1000 ng/天，每天 3 次） 3 个月，每周 3 次；40、200 或 1000 ng/天，每周 3 次，持续 6 个月）。没有观察到死亡率、明显的全身或消化毒性。在这两种菌株中都记录了肠道微生物群的剂量依赖性改变。在 ApoE-/- 中，β-多样性被 DEP 修改，但没有发现门、科或属的相对丰度的显着改变。在 C57BL/6 小鼠中，DEP 降低了 α-多样性（香农和辛普森指数），并改变了 β-多样性，包括变形杆菌和 Patescibacteria 门的减少，以及弯曲杆菌门的增加。在这两种小鼠模型中，肠道微生物群组成的扰动与盲肠内容物中细菌短链脂肪酸（丁酸和丙酸）的剂量依赖性降低有关。然而，摄入 DEP 不会加重（ApoE-/-）或诱导（C57BL/6 小鼠）动脉粥样硬化斑块，并且没有记录到代谢改变（葡萄糖耐量、胰岛素抵抗或血脂）。我们在此表明​​，以与人类健康相关的剂量口服暴露于 DEP 会改变肠道微生物群的组成和功能。然而，这些修改并未转化为最终的动脉粥样硬化或代谢结果。