Impact of air pollution on intestinal redox lipidome and microbiome

Highlights

• Air pollution exposure is associated with the incidence of intestinal disease.

• Air pollution promotes the production of pro-inflammatory oxidative lipids.

• Air pollution alters the composition/diversity of gut microbiota.

• Air pollution-mediated alterations of microbiome might affect lipid metabolism.

Abstract

Air pollution is a rising public health issue worldwide. Cumulative epidemiological and experimental studies have shown that exposure to air pollution such as particulate matter (PM) is linked with increased hospital admissions and all-cause mortality. While previous studies on air pollution mostly focused on the respiratory and cardiovascular effects, emerging evidence supports a significant impact of air pollution on the gastrointestinal (GI) system. The gut is exposed to PM as most of the inhaled particles are removed from the lungs to the GI tract via mucociliary clearance. Ingestion of contaminated food and water is another common source of GI tract exposure to pollutants. Recent studies have associated air pollution with intestinal diseases, including appendicitis, colorectal cancer, and inflammatory bowel disease. In addition to the liver and adipose tissue, intestine is an important organ system for lipid metabolism, and the intestinal redox lipids might be tightly associated with the intestinal and systematic inflammation. The gut microbiota modulates lipid metabolism and contributes to the initiation and development of intestinal disease including inflammatory bowel disease. Recent data support microbiome implication in air pollution-mediated intestinal and systematic effects. In this review, the associations between air pollution and intestinal diseases, and the alterations of intestinal lipidome and gut microbiome by air pollution are highlighted. The potential mechanistic aspects underlying air pollution-mediated intestinal pathology will also be discussed.

Introduction

Air pollution has long been recognized as a risk factor for multiple diseases, increasing hospital admissions and all-cause mortality [1]. The World Health Organization ranks it as the 13th leading cause of worldwide mortality [2]. Cumulative evidence over the last two decades has linked air pollution with respiratory diseases such as asthma [3], cardiovascular diseases such as myocardial infarction and stroke [4], metabolic disorders such as obesity and diabetes [5], and cancers [6]. Air pollution is composed of a number of substances including gaseous components (e.g., carbon monoxide, carbon dioxide, ozone, nitric oxide, and sulfur dioxide), volatile organic compounds (e.g., benzene, acetone, and ethyl acetate), and particulate matter (PM), each of which has deleterious effects on human health [7]. The specific composition of air pollution varies across different locations, which results in great difficulties in the standardization of air pollution components and study design. The two most studied air pollutants are ozone and PM. Ozone-induced inflammation and tissue damage lead to the breakdown of tight junction integrity and increased cell permeability, which has been observed in both humans and animal models [8]. PM, the major component of adverse health effects by air pollution, contains a mixture of pollen, sulfates, nitrates, organic carbon, mineral dust, polycyclic aromatic hydrocarbons (PAHs), metals, ions, microbial particles, and spores, etc [9]. Sources of PM range from the combustion of fossil fuels (e.g., diesel exhaust, industrial emissions) to road dust and windblown soil [9]. According to the particle diameter, PM can be sub-classified into three categories, ultrafine particles (UFP, diameter <100 nm), fine particles (PM_2.5, diameter < 2.5 μm), and coarse particles (PM₁₀, diameter < 10 μm) [9]. PM with different sizes appears to possess different abilities to cause harmful effects. There is increasing evidence that particles with a smaller size pose a higher risk because of their high content of organic chemicals and pro-oxidative potential [10]. For example, UFP-exposed mice seem to develop accelerated atherosclerosis as compared to the PM_2.5-mice [11].

In comparison to a plethora of studies investigating air pollution-mediated respiratory and cardiovascular diseases, there remains a paucity of literature examining the impact of air pollution on the intestinal system. With increasing epidemiological studies linking air pollution with pathologies of the gastrointestinal (GI) tract, how air pollutants exert their effects on the intestinal system has gained more attention in recent years. The GI tract is readily exposed to air pollutants through direct or indirect routes. Inhaled particles are quickly cleared from the lungs to the intestine by mucociliary transport [12]. After the initial inhalation, the localization of the inhaled particles varies depending on their size. Larger particles are more likely sequestered in the upper respiratory tract or the conducting lower airway, while smaller particles, especially those with an average diameter of less than 2.5 μm, could be engulfed by macrophage in the bronchioles and alveolar spaces [13]. The particles sequestered by the macrophages adsorbed in the mucus layer of the lower airways are then transported back to the oropharynx and consequently swallowed into the GI tract [14]. Another mechanism whereby PM gains access to the GI tract is by the direct dietary ingestion of food and water contaminated with urban and industrial air pollutants [15]. Within a typical Western diet, an individual consumes nearly 10¹²-10¹⁴ particles per day [16,17]. In addition, gaseous pollutants can also exert an impact on the GI tract through the induction of systematic inflammation [18]. Thus, the GI tract might be an important organ system in which air pollution incurs local inflammatory and redox responses, along with changes in the microbiota diversity (dysbiosis) to release cytokines and lipid metabolites to the systematic circulation. In this review, we introduce the links between air pollution and intestinal diseases, followed by highlighting the impact of air pollution on intestinal lipidome and microbiome.