Growing evidence suggests physiological and pathological functions of lung and gut microbiomes in various pathologies. Epidemiological and experimental data associate air pollution exposure with host microbial dysbiosis in the lungs and gut. Air pollution through increased reactive oxygen species generation, the disruption of epithelial barrier integrity, and systemic inflammation modulates microbial imbalance. Microbiome balance is crucial in regulating inflammation and metabolic pathways to maintain health. Microbiome dysbiosis is proposed as a potential mechanism for the air-pollution-induced modulation of pulmonary and systemic disorders. Microbiome-based therapeutic approaches are increasingly gaining attention and could have added value in promoting lung health. This review summarizes and discusses air-pollution-mediated microbiome alterations in the lungs and gut in humans and mice and elaborates on their role in health and disease. We discuss and summarize the current literature, highlight important mechanisms that lead to microbial dysbiosis, and elaborate on pathways that potentially link lung and lung microbiomes in the context of environmental exposures. Finally, we discuss the lung–liver–gut axis and its potential pathophysiological implications in air-pollution-mediated pathologies through microbial dysbiosis.

Oxidation of engineered nanomaterials during application in various industrial sectors can alter their toxicity. Oxidized nanomaterials also have widespread industrial and biomedical applications. In this study, we evaluated the cardiopulmonary hazard posed by these nanomaterials using oxidized carbon black (CB) nanoparticles (CB_ox) as a model particle.

Air pollution poses a significant threat to public health. It is a mixture of particulate matter, gaseous substances, and other secondary substances. Despite epidemiological research indicating the interactive effects of various components of air pollution, existing studies and regulatory limits often focus on single-exposure scenarios. The emerging understanding of the microbiome’s role in regulating immune response, metabolism, and pathophysiology of various diseases points towards interactions between environmental exposures and microbial dysbiosis. In this dissertation, mice were exposed to relevant deposited doses of carbon black (CB) and ozone (O3), and lung inflammation as well as the lung-gut axis of the microbiome alterations were studied. We also studied the role of nucleotide-biding oligomerization domainlike receptor X1 (NLRX1) in mechanistically modulating immune response and microbial balance. Our project involved inhalation exposures, a unique mouse model (NLRX1 knock out), flow cytometric analysis of immune cells, 16s rRNA sequencing, and absolute bacterial load analysis using QIAcuity digital PCR. We demonstrated significant induction of pulmonary inflammatory response after acute CB+O3 co-exposure coupled with reduced diversity indices and a pathogenic bacterial enrichment in the lung microbiome. In contrast, a significant increase in gut bacterial load, abundance of beneficial bacteria, and induction of microbiome-derived secondary metabolites in the systemic circulation indicated a homeostatic shift. Sub-chronic exposure to CB+O3 did not show significant alterations in the inflammatory response and microbiome balance. However, aggravated inflammatory response and microbiome alterations were observed when lungs were challenged with bleomycin post-exposure. A significant role of genetics, exposure, and sex was observed that changed dynamically at different post-exposure time points. In summary, these studies improved the current understanding of particle and gas mixed exposures in terms of their impacts on immune cell profiling, oxidative stress, and microbiome regulation. Furthermore, our project highlighted the role of microbiome alterations in the air pollution-induced exacerbation of lung inflammation and injury identifying a potential role of the lung-gut axis.