长期接触细颗粒物(PM2.5)对胃肠道和呼吸系统造成伤害,归因于肺肠轴。然而,串扰机制仍不清楚。这里,我们试图在环境水平下建立暴露于PM2.5的小鼠的肺-肠轴反应网络。雄性Balb/c小鼠暴露于从成都采集的PM2.5(剂量为0.1、0.5和1.0mg/kg),中国10周,通过气管内滴注,研究了PM2.5对小鼠肺功能的影响。测定不同组小鼠肺部和肠道菌群变化及代谢谱。此外,我们对多组学的结果进行了联合分析,以阐明导致PM2.5暴露的肺和肠道中的主要微生物和相关代谢产物.因此,建立了肺-肠轴之间的串扰网络和关键通路.结果表明,暴露于0.1mg/kg的PM2.5会引起小鼠肺部明显的炎症,而肺气肿的浓度为1.0mg/kg。代谢物鸟苷的水平,次黄嘌呤,暴露组肺部HepoxilinB3增加可能导致肺部炎症。对于肺部的微生物,PM2.5暴露显著降低了盐单胞菌和乳酸菌的比例。同时,肠道中的代谢产物,包括L-色氨酸,血清素,亚精胺在暴露组中上调,这与肠道中螺旋体和螺杆菌的减少有关。通过肺肠轴,包括色氨酸代谢在内的途径的激活,ABC运输商,血清素能突触,和亚油酸代谢有助于PM2.5介导的小鼠肺和肠组织之间的串扰。总之,包括乳酸菌在内的微生物,螺旋体,和副杆菌属,和代谢物包括hepoxilinB3,鸟苷,次黄嘌呤,L-色氨酸,亚精胺是主要驱动因素。在这项肺-肠轴研究中,我们阐明了肺和肠道微环境中的一些益生菌和益生元导致了PM2.5暴露对肺功能的不利影响.
Long-term exposure to fine particulate matter (PM2.5) posed injury for gastrointestinal and respiratory systems, ascribing with the lung-gut axis. However, the cross-talk mechanisms remain unclear. Here, we attempted to establish the response networks of lung-gut axis in mice exposed to PM2.5 at environmental levels. Male Balb/c mice were exposed to PM2.5 (dose of 0.1, 0.5, and 1.0 mg/kg) collected from Chengdu,
China for 10 weeks, through intratracheally instillation, and examined the effect of PM2.5 on lung functions of mice. The changes of lung and gut microbiota and metabolic profiles of mice in different groups were determined. Furthermore, the results of multi-omics were conjointly analyzed to elucidate the primary microbes and the associated metabolites in lung and gut responsible for PM2.5 exposure. Accordingly, the cross-talk network and key pathways between lung-gut axis were established. The results indicated that exposed to PM2.5 0.1 mg/kg induced obvious inflammations in mice lung, while emphysema was observed at 1.0 mg/kg. The levels of metabolites guanosine, hypoxanthine, and hepoxilin B3 increased in the lung might contribute to lung inflammations in exposure groups. For microbiotas in lung, PM2.5 exposure significantly declined the proportions of Halomonas and Lactobacillus. Meanwhile, the metabolites in gut including L-tryptophan, serotonin, and spermidine were up-regulated in exposure groups, which were linked to the decreasing of Oscillospira and Helicobacter in gut. Via lung-gut axis, the activations of pathways including Tryptophan metabolism, ABC transporters, Serotonergic synapse, and Linoleic acid metabolism contributed to the cross-talk between lung and gut tissues of mice mediated by PM2.5. In summary, the microbes including Lactobacillus, Oscillospira, and Parabacteroides, and metabolites including hepoxilin B3, guanosine, hypoxanthine, L-tryptophan, and spermidine were the main drivers. In this lung-gut axis study, we elucidated some pro- and pre-biotics in lung and gut microenvironments contributed to the adverse effects on lung functions induced by PM2.5 exposure.