Non-neoplastic digestive system diseases (NNDSD) are non-cancerous digestive disorders, encompassing conditions such as gastroenteritis, gastroesophageal reflux disease (GERD), inflammatory bowel disease (IBD), irritable bowel syndrome (IBS), and liver diseases, among others (1, 2). There were 100,317 deaths related to non-malignant gastrointestinal diseases in the United States in 2019 (3). The incidence of digestive disorders has been increasing in China and other countries with Western societies (4). Research is increasingly revealing a pathogenic continuum between certain NNDSD and the emergence of malignant tumors of the gastrointestinal tract (5, 6). Millions worldwide suffer from these diseases, which also impose significant economic burdens, including high medical costs and lost work hours (7). Consequently, NNDSD represents a significant aspect of public health, and identifying risk factors for NNDSD is crucial for preventing and controlling NNDSD.

Industrialization, urbanization, and urban population growth have made air pollution one of the most critical environmental factors (8). Exposure to chronic air pollution [particulate matter with a diameter ≤ 2.5 μm (PM_2.5) or ≤10 μm (PM₁₀), sulfur dioxide (SO₂), nitrogen dioxide (NO₂), ozone (O₃), and carbon monoxide (CO)] has been associated with respiratory diseases, cardiometabolic diseases, and cancer (9–12). Air pollution has been linked to digestive disorders such as enteritis, appendicitis, IBD, liver disease, and peptic ulcers. An association has been established between air pollution exposure and a higher incidence of NNDSD in urban populations (13–15). Our methodology extends previous research by incorporating a broader spectrum of air pollutants and a larger sample size. Prior studies primarily focused on PM_2.5 and its impacts; our study included comprehensive pollutants such as PM₁₀, SO₂, NO₂, O₃, and CO, allowing for a more detailed analysis of air quality impacts on NNDSD. The effects of air pollution on digestive diseases have also been studied from a mechanistic perspective. Environmental exposure directly impacts epithelial cells, increases intestinal permeability, induces oxidative stress, triggers systemic inflammation, and alters gut microbiota (16–18). Despite their prevalence, the link between environmental factors, especially air pollution, and NNDSD remains largely unexplored. Particularly evident is this gap in China and other developing countries, where air pollution levels are high and large-scale population-based studies are lacking.

We conducted a national cross-sectional study to investigate the relationship between six major air pollutants (PM_2.5, PM₁₀, SO₂, NO₂, O₃, and CO) and NNDSD to develop feasible strategies for preventing and controlling the disease.

This study was one of the few national epidemiologic studies in China that investigated the relationship between continuous exposure to air pollutants and NNDSD. The purpose of this study was to investigate the effects of PM_2.5, PM₁₀, SO₂, NO₂, O₃, and CO on NNDSD among middle-aged and older adult Chinese residents. Our findings revealed significant associations between several common air pollutants and the risk of NNDSD, with varying strengths across different pollutants. Nearly the entire global population is exposed to airborne pollution, recognized as a significant environmental health risk (19). In terms of policymaking aimed at protecting the public health from air pollution, our findings supported the hypothesis that air pollution exposure adversely affects NNDSD.

PM_2.5 and PM₁₀ are particulate air pollutants. Our study revealed that PM_2.5 and PM₁₀ demonstrate the strongest correlation in Pearson correlation analysis. Current research established a significant association between PM₁₀ and NNDSD, persisting even after adjustment for confounding factors. Conversely, PM_2.5 showed significant associations only in crude and base models, failing to maintain statistical significance in the main model. There appeared to be a difference in impact between air pollution particles of different sizes on digestive system health, with PM₁₀ having a more pronounced effect in our study population than PM_2.5.

This observation was corroborated by prior research. A comprehensive cross-sectional analysis involving 90,086 participants in southwest China demonstrated a positive association between prolonged exposure to environmental particulate matter and metabolically associated fatty liver disease. Additionally, animal studies have identified a steatohepatitis-like phenotype and liver fibrosis associated with such exposures, reinforcing the broader implications of particulate pollutants on liver health (20, 21). According to a cross-sectional study conducted in the United States, hospitalized patients with higher ambient PM_2.5 exposure were more likely to develop non-alcoholic fatty liver disease (22). An extensive nationwide time-series study examined the adverse effects of short-term PM_2.5 exposure on various digestive disorders, including intestinal infections, esophageal disease, gastritis, appendicitis, liver disease, gastrointestinal bleeding, and non-infectious gastroenteritis (23). On cooler days, there has been a significant increase in peptic ulcer hospitalizations in Taipei with rising levels of PM₁₀ (24).

Research indicated that the impact of particulate air pollutants on the digestive system was primarily mediated through the ingestion of contaminants in food and water, as well as the direct effects of gaseous pollutants on the gastrointestinal tract during swallowing (25, 26). The deposition of air pollution particles in the lungs and the resultant epithelial cell responses, including the production of free radicals and inflammation, lead to the disruption of the alveolar barrier. These factors can subsequently enter the bloodstream, directly affecting intestinal epithelial cells and increasing intestinal permeability (27–30). Additionally, exposure to PM_2.5 was associated with elevated levels of cluster of differentiation and systemic inflammation (31, 32). Animal studies demonstrate that PM₁₀ exposure in mice leads to elevated pro-inflammatory cytokine levels in the small and large intestines, potentially stimulating alveolar macrophages to produce inflammatory factors present in the bloodstream during air pollution episodes (33, 34). Furthermore, studies have found that particulate air pollutants significantly altered the gut microbiota composition in both animals and humans, potentially increasing susceptibility to mucosal inflammation (17, 28, 30, 35).

We found a close association between SO₂ levels and an increased risk of NNDSD. In subgroup and interaction analysis, we observed that the impact of environmental air pollutant SO₂ on NNDSD was more pronounced among subjects with higher education. Residents near the Madin Dam in the State of Mexico showed a significant correlation between chronic exposure to SO₂ and liver function impairment. Specifically, individuals exposed to high levels of SO₂ exhibit elevated levels of lipid peroxidation products and oxidative stress markers in their blood, which are biomarkers indicating hepatocellular damage and dysfunction (36). In a study involving more than 2.7 million adults in Northwest China, each 10 μg/m³ increase in SO₂ concentration was associated with a 2.7-fold increase in the incidence risk of metabolically associated fatty liver disease (37). The increase in SO₂ levels have exacerbated inflammation and oxidative stress in the liver, both key drivers in the development of metabolically associated fatty liver disease. Research on pregnant women found that an increase in environmental SO₂ levels during the second trimester was associated with an increased risk of intrahepatic cholestasis of pregnancy (38). Long-term exposure to SO₂ may have increased pro-inflammatory cytokines such as IL-6 and IL-1β, and decreased hepatic bile transport proteins, leading to the accumulation of bile acids in the liver (39, 40).

A significant association between NO₂ levels and NNDSD was observed. In our main model, an increase in NO₂ exposure by one IQR was associated with a 30% increase in risk. An analysis of 8,566 older adult cases recorded between 2005 and 2010 by Tian et al. (41) found that a short-term increase in ambient NO₂ levels may have increased the risk of peptic ulcer bleeding and related hospitalizations in Hong Kong’s older adult population. In a large-scale cohort study that investigated the associations between air pollutants and the risk of 12 gastrointestinal diseases, positive correlations were observed between NO₂ and NOx with the risk of peptic ulcers and chronic gastritis (42). According to other studies, long-term exposures to NO₂ were associated with ulcerative colitis but not Crohn’s disease (43). Research involving 329,048 adults in Taiwan and Hong Kong between 2001 and 2018 demonstrated that rising concentrations of NO₂ were linked to an increased risk of Non-Alcoholic Fatty Liver Disease (NAFLD) and its associated advanced fibrosis (44). Empirical evidence on the relationship between NO₂ and digestive system diseases remained limited. As a component of traffic-related air pollution, NO₂ was also found to be associated with elevated levels of cytokeratin-18, which may be linked to liver damage (45). NO₂ swallowed through belching may trigger a nitrification reaction in the stomach, leading to redox interactions that disrupt the intestinal lining and promote gastrointestinal diseases (46).

Our study found that exposure to O₃ is significantly associated with NNDSD, especially among smokers and those who are married or cohabiting. One research has shown that for every one standard deviation increase in O₃ concentration, NAFLD decreases by 12%, and the incidence of advanced fibrosis decreases by 11%. This suggested that higher levels of O₃ might have a protective effect against these conditions (44). Conversely, a study from Northwest China indicated that elevated O₃ levels were linked to a slight increase in the risk of Metabolically Associated Fatty Liver Disease (37). Additionally, research from Korea reported a positive correlation between short-term exposure to O₃ and elevated levels of gamma-glutamyl transferase (47). An analysis of the 7-day cumulative average of terrestrial O₃ conducted by a Canadian researcher suggests that higher levels of environmental O₃ exposure may increase the risk of perforated appendicitis (48). Kaplan’s findings indicated that higher 5-day average ozone levels increased appendicitis rates, especially in summer, with a greater impact on younger individuals than older adults. The specific mechanisms by which O₃ influenced appendicitis incidence remained unclear, but inhaling or ingesting air pollutants likely triggered inflammatory responses in humans (49). Himuro (50) demonstrated that intrarectal administration of ozone gas causes transient epithelial cell damage, which is specifically caused by damage to DNA replication and cell cycle pathways. Exposure to O₃ stimulated the production of tumor necrosis factors IL-6 and IL-8 and promotes systemic inflammation in humans, which may be a key factor in the pathogenesis of these diseases (51, 52).

In our study, exposure to CO was associated with an increased risk of NNDSD. There is limited literature on the impact of CO on digestive system disorders. Chinese researchers found that CO levels were significantly elevated on days of outpatient visits for enterocolitis (53). A study in Yichang, China, demonstrated that for every 1 mg/m³ increase in CO levels, there is a 19.04% (95% CI: 8.39, 29.68%) rise in daily outpatient visits for gastrointestinal diseases. From 2002 through 2007, Seo et al. (54) found that CO may increase the risk of GERD based on medical utilization data from the National Health Insurance Institute of Korea. Short-term exposure to CO air pollution was associated with decreased microvascular endothelial function (55). Microvascular dysfunction may have contributed to poor mucosal healing, refractory inflammatory ulcers, and intestinal injury in IBD patients, resulting in diminished vasodilatory capacity and inadequate tissue perfusion (56). CO’s high affinity for myoglobin may cause weakness in the lower esophageal sphincter, potentially leading to myasthenia gravis (57).

Our findings underscored the broader public health implications, suggesting that reducing air pollution levels could alleviate the burden of digestive system diseases among adults, particularly in areas with high pollution. Although many epidemiological studies link sustained air pollutant exposure to NNDSD risk, the underlying biological mechanisms remain unclear (58, 59). A biological and epidemiological study will be necessary to elucidate the mechanisms by which air pollution affects cognitive function in the future.

There are several advantages to our study. Firstly, it is a nationwide study conducted in China, it offers a high level of generalizability. Secondly, this is the first study to investigate the relationship between air pollution exposure and NNDSD. Furthermore, we considered more air pollutants than previous studies, including the rarely considered NO₂. However, we also have some limitations to our study. While we used satellite-based spatio-temporal modeling to estimate air pollution levels, exposure assessments were based on community locations, which may not fully represent individual exposures. Additionally, many individuals were excluded due to missing data on the variables, which may have led to a selection bias. Lastly, the findings may be affected by questionnaire and recall bias among older subjects. A lack of detailed types of NNDSD in this study also prevented a detailed study of life environmental factors on specific subtypes of NNDSD.

Our study suggests that chronic exposure to ambient air pollution may increase the prevalence of NNDSD among adults aged 45 and older in China. Particulates and gaseous pollutants like PM_2.5, PM₁₀, SO₂, NO₂, O₃, and CO are significantly associated with NNDSD. This underscores the need for targeted air quality policies, which could reduce the NNDSD burden and prevent many cases.