Toxic and essential metals: metabolic interactions with the gut microbiota and health implications

Abstract

Human exposure to heavy metals, which encompasses both essential and toxic varieties, is widespread. The intestine functions as a critical organ for absorption and metabolism of heavy metals. Gut microbiota plays a crucial role in heavy metal absorption, metabolism, and related processes. Toxic heavy metals (THMs), such as arsenic (As), mercury (Hg), lead (Pb), and cadmium (Cd), can cause damage to multiple organs even at low levels of exposure, and it is crucial to emphasize their potential high toxicity. Nevertheless, certain essential trace elements, including iron (Fe), copper (Cu), and manganese (Mn), play vital roles in the biochemical and physiological functions of organisms at low concentrations but can exert toxic effects on the gut microbiota at higher levels. Some potentially essential micronutrients, such as chromium (Cr), silicon (Si), and nickel (Ni), which were considered to be intermediate in terms of their essentiality and toxicity, had different effects on the gut microbiota and their metabolites. Bidirectional relationships between heavy metals and gut microbiota have been found. Heavy metal exposure disrupts gut microbiota and influences its metabolism and physiological functions, potentially contributing to metabolic and other disorders. Furthermore, gut microbiota influences the absorption and metabolism of heavy metals by serving as a physical barrier against heavy metal absorption and modulating the pH, oxidative balance, and concentrations of detoxification enzymes or proteins involved in heavy metal metabolism. The interactions between heavy metals and gut microbiota might be positive or negative according to different valence states, concentrations, and forms of the same heavy metal. This paper reviews the metabolic interactions of 10 common heavy metals with the gut microbiota and their health implications. This collated information could provide novel insights into the disruption of the intestinal microbiota caused by heavy metals as a potential contributing factor to human diseases.

Keywords: essential trace elements; gut microbiota; health implications; metabolites; toxic heavy metals.

Figure 1

The main physiological functions and potential toxic effects of heavy metals. Heavy metals are categorized into essential trace elements and toxic heavy metals according to whether there is a threshold for toxicity and their physiological functions in the human body. The toxicity and their possible molecular mechanisms are listed on the right side of the circle, while the main physiological functions of essential trace elements and their possible hazards caused by excessive amounts are listed on the left side of the circle.

Figure 2

Metal-gut microbiome interactions. The gut microbiota modulate metal toxicity through biotransformation (such as reduction, oxidation, methylations, or demethylations), alter the absorption and metabolism of HMs by modifying the PH and oxidative balance of the gut and the expression of detoxification enzymes or proteins involved in HM metabolism. Heavy metals exposure can alter the composition (abundance, diversity), and metabolic activities of gut microbiota. Dysbiosis and gut barrier disruption may activate the immune system, lead to metabolic and other disorders.