Nutritional interventions to prevent inflammatory diseases linked to exposure to environmental toxins in food

Abstract

The pathologies of many inflammatory diseases such as atherosclerosis are independently associated with genetic and lifestyle factors (Du & Ha, 2020; Jane et al., 2022; Li et al., 2023; Morgan et al., 2023), suggesting that potential biological interactions between chemical and nonchemical stressors and buffers will determine disease outcome. Chemical stressors include persistent organic pollutants (POPs) such as dioxin-like polychlorinated biphenyls (PCBs) or per- and polyfluoroalkyl substances (PFASs), as well as air pollutants and both gaseous and particulate matter, which all can contribute to changes in the cellular redox status and thus to inflammation (Lee et al., 2018; Peters et al., 2021). For example, human PFASs exposure appears to be associated with perturbation of key hepatic metabolic pathways in nonalcoholic fatty liver disease (Sen et al., 2022). In addition, a cross-sectional analysis revealed that long-chain PFASs were related to plaque occurrence (Lind et al., 2017). Mechanistic studies suggest that exposures to environmental pollutants could activate oxidative stress, resulting in inflammation by damaging the scavenging ability of antioxidant enzymes (e.g., superoxide dismutase or SOD) and thus causing the modification or dysregulation of downstream nuclear factor-κB (NF-κB)/tumor necrosis factor-α or Nrf2 signal pathways, as well as inducing the production of transcription of cytokines, chemokines, antimicrobial peptides, and antiapoptotic proteins (He et al., 2022; Mudway et al., 2020; Peters et al., 2021).

Major routes of exposure to environmental pollutants are through contaminated food and water (Guo et al., 2019; Saravanan et al., 2022), and many environmental pollutants or toxicants are ubiquitous with long half-lives. Environmental toxicants in food sources also are often derived from industrial sources and from processed and packaged foods, for example, through food processing, packaging, transportation, and storage. PFASs are an example of environmental pollutants found not only in processed food and grease-resistant packaging of food but also in equipment used to prepare such food products (van Asselt et al., 2013; Zabaleta et al., 2016). In addition, the use of soil and water contaminated with PFAS to grow crops and feed animals intended for human food consumption can lead to PFAS entering the food supply. Therefore, exposure to environmental pollutants, and in particular POPs, is often unavoidable and a major contributor to inflammatory diseases, such as cardiovascular disease, obesity, and diabetes (Guo et al., 2019).

Even though this commentary focuses on persistent environmental pollutants as a source of environmental toxins in foodstuffs, mycotoxins in contaminated foods can also contribute to serious health hazards in mammals (Kumar, et al., 2022a; Kumar et al., 2022b). Mycotoxins are secondary metabolites produced by fungi, for example, Aspergillus, Fusarium, Neurospora, Penicillium, and so on, mostly during milling and preparation of grain and grain products and during transportation and storage of these food products. Some mycotoxins have high stability and are difficult to remove from human food sources and animal feed, and thus can add significantly to diseases associated with exposure to environmental pollutants or toxins. For example, aflatoxin B1 is one of the most toxic mycotoxins that can lead to the development of hepatocellular carcinoma by promoting DNA adduct formation, inflammation, and oxidative stress (Cao et al., 2022).

It has become increasingly clear that the human gut microbiota plays a crucial role in host response to environmental insult, especially during pollutant exposure via ingestion of contaminated food products. Our data, including metabolomic, lipidomic, transcriptomic, and metagenomic analyses, suggest that gut microbiota is a major player in the pathology of POP-mediated inflammatory diseases, which may involve disturbances within multiple organ systems, including liver, adipose, and vascular tissues (Deng et al., 2019, 2020, 2022; Petriello et al., 2018). In addition, there is accumulating evidence suggesting that prebiotics and probiotics can modulate environmental pollutant-induced disease risks. For example, dietary fibers such as prebiotics (inulin or pectin) can protect against perfluorooctane sulfonic acid- and PCB 126-induced hepatic metabolism disturbances (Deng et al., 2022; Hoffman et al., 2020). Many environmental pollutants and proatherosclerotic diets can activate NF-ĸB signaling, leading to increased oxidative stress and inflammation (Wang et al., 2019). Antioxidant or anti-inflammatory nutrients, such as plant-derived phytochemicals (proanthocyanidins, sesamin, green tea extract, etc.), can decrease inflammation by activating Nrf2 signaling or by attenuating oxidative stress (Newsome et al., 2014; Ren et al., 2021; Zhang et al., 2021).

To decrease exposure to environmental pollutants or chemical/biological stressors, there is a need to reduce toxic chemicals in food sources, particularly in processed foods, and to explore intervention and/or prevention measures targeting gut and systemic inflammations (Figure 1). This could be through positive lifestyle changes such as healthful nutrition, which means an increase in the consumption of freshly prepared whole foods rich in protective bioactive phytochemicals and soluble fibers and a decrease in the consumption of processed and ready-to-eat packaged food, often contaminated with environmental toxicants. Of special interest are approaches of intervention/prevention by modulating the gut microbiome to improve gut health and lower disease outcome linked to complex interactions of chemical stressors with multiple organs.