The gut microbiota: A key player in cadmium toxicity - implications for disease, interventions, and combined toxicant exposures.

Cadmium (Cd) is a highly toxic heavy metal contaminant found in soil and water due to human activities such as mining and industrial discharge. Cd can accumulate in the body, leading to various health risks such as organ injuries, osteoporosis, renal dysfunction, Type 2 diabetes (T2DM), reproductive diseases, hypertension, cardiovascular diseases, and cancers. The gut is particularly sensitive to Cd toxicity as it acts as the primary barrier against orally ingested Cd. Even at low concentrations, Cd can cause oxidative stress, inflammation, and intestinal bleeding. Cd also disrupts the gut microbiota, affecting its structure, taxonomic composition, and metabolic functions. Cd exposure alters the structure of the gut microbial community, reducing diversity and upregulating certain phyla and genera. This disturbance can lead to physiological and metabolic imbalances, including disruptions in energy homeostasis, amino acid, lipid, nucleotide, and short-chain fatty acid (SCFAs) metabolism. The effects of Cd on the gut microbiota depend on the duration of exposure, the dose of Cd, and can vary based on sex and age. Cd-induced gut dysbiosis has been linked to various diseases, including diabetes, adiposity, atherosclerosis, liver damage, infections, cancer, and neurodegenerative diseases. Interventions targeting the gut microbiota, such as probiotics, specific diets, melatonin, selenium, vitamin D3, and certain compounds, have shown potential in reducing the health risks associated with Cd exposure. However, combined exposure to Cd and other toxicants, such as microplastics (MPs), heavy metals, and antibiotics, can amplify the toxicity and dysbiosis in the gut microbiota.