Toxins to treatments: Impact of environmental pollutants, gut microbiota, and natural compounds on non-alcoholic fatty liver disease progression

Non-alcoholic fatty liver disease (NAFLD) is the fastest-growing global contributor to the disease burden associated with the consequences of chronic liver disease, including cirrhosis and liver cancer. It is projected that more than fifty percent of the adult population, including women, smokers, and individuals without metabolic syndrome, will have NAFLD by 2040. Various mechanisms linking the gut microbiome to NAFLD and the consequent fibrosis have been discerned, which suggest the dysbiosis-induced impairment of gut endothelial barrier function, leading to hepatic inflammation through the translocation of bacterial components. NAFLD is progressively associated with environmental variables, especially exposure to heavy metals that impair liver metabolism, produce oxidative stress, and exacerbate inflammation, hence accelerating its progression. These toxicants also modify the composition of gut microbiota, hence intensifying liver damage. Comprehending the processes by which heavy metals contribute to NAFLD is essential for formulating tailored therapies. This review examines strategies to alleviate liver toxicity caused by heavy metals, including chelation therapy, dietary modifications (antioxidants and hepatoprotective nutrients), gut microbiome modulation via probiotics and postbiotics like short-chain fatty acids to restore intestinal barrier function and use of essential minerals like selenium, with potent antioxidant characteristics. Employing these measures may offer an integrated approach for addressing NAFLD in individuals subjected to heavy metal poisoning.