The Role of the Human Microbiome in Chemical Toxicity

Abstract

There is overwhelming evidence that the microbiome must be considered when evaluating the toxicity of chemicals. Disruption of the normal microbial flora is a known effect of toxic exposure, and these disruptions may lead to human health effects. In addition, the biotransformation of numerous compounds has been shown to be dependent on microbial enzymes, with the potential for different host health outcomes resulting from variations in the microbiome. Evidence suggests that such metabolism of environmental chemicals by enzymes from the host's microbiota can affect the toxicity of that chemical to the host. Chemical-microbial interactions can be categorized into two classes: Microbiome Modulation of Toxicity (MMT) and Toxicant Modulation of the Microbiome (TMM). MMT refers to transformation of a chemical by microbial enzymes or metabolites to modify the chemical in a way that makes it more or less toxic. TMM is a change in the microbiota that results from a chemical exposure. These changes span a large magnitude of effects and may vary from microbial gene regulation, to inhibition of a specific enzyme, to the death of the microbes. Certain microbiomes or microbiota may become associated with different health outcomes, such as resistance or susceptibility to exposure to certain toxic chemicals, the ability to recover following a chemical-induced injury, the presence of disease-associated phenotypes, and the effectiveness of immune responses. Future work in toxicology will require an understanding of how the microbiome interacts with toxicants to fully elucidate how a compound will affect a diverse, real-world population.

Species Differences in in vitro and Estimated in vivo Kinetics for Intestinal Microbiota Mediated Metabolism of Acetyl‐deoxynivalenols

“…Evidence is accumulating on the efficient conversion of acetylated forms of DON to DON by intestinal microbiota. [ 9,10,19 ] However, so far, to the best of our knowledge, kinetics of this process by microbiota from different host species have not been defined. Hence the present study aimed to assess the interspecies deacetylation kinetic constants for conversion of the major food‐borne acetyl‐DONs, i.e., 3‐Ac‐DON and 15‐Ac‐DON.…”

Targeting gut microbiota for precision medicine: Focusing on the efficacy and toxicity of drugs

“…In vitro and in vivo studies have demonstrated that gut microbiota can modulate the toxicity of arsenic via direct metabolism of arsenic (including oxidative methylation and glutathione conjugation), and this process also increases the bioavailability of arsenic 65 , 66 . In addition to arsenic, it has been proven that gut microbiota can metabolize other heavy metals such as mercury and chromium, and thus change their bioavailability 67 .…”

Role of the Microbiome as the First Metal Detoxification Mechanism

“…These occur in the liver and kidney, but various biotransformation reactions in the intestine can also be carried out through the microbiota. In this context, there is evidence at the preclinical level in cell cultures and in animal models that the microbiota performs various chemical reactions that can modify the toxicity of heavy metals; since heavy metals when distributed in the body can be concentrated in the bile and subsequently enter the enterohepatic circuit, or during their journey through the gastrointestinal system they may be susceptible to being biotransformed by the microbiota enzymes to less or more compounds toxic to the individual and even to the microbiota itself [35,36]. This is a new issue that is changing the approach to toxicokinetics and toxicodynamics of heavy metals and other environmental toxins.…”