The Role of the Human Microbiome in Chemical Toxicity

From International Journal of Toxicology
Published in Association with American College of Toxicology

By Dr. Mary Beth Genter

“It has been reported that the human body contains more non-human cells than human cells! Who are these intruders, why are they there, and how do they respond to chemical exposures? And also importantly, how are chemicals affected by the presence of our most welcome intruders?

A recent International Journal of Toxicology (IJT) review article addressed some of these questions. As to the identity of the intruders, the human gastrointestinal tract is estimated to contain over 1,000 unique bacterial species, which not only affect levels of important metabolites in the human body, but also can biotransform orally-ingested materials (or other materials entering the gut via other routes, such as those contained in bile).

So these quick facts, in a very simple fashion, partially answer the “who” and the “what are they doing” questions, so we’ll now turn to the IJT article to learn the impact of chemicals on the microbiome, and the effects of the microbiome on chemicals. Chemical-microbial interactions can be categorized into two categories: Microbiome Modulation of Toxicity (MMT) and Toxicant Modulation of the Microbiome (TMM). These terms refer to biotransformation (metabolism) of a chemical by microbial enzymes to alter the chemical’s toxicity (MMT), and the change in the microbiota that results from chemical exposures (TMM). The concept of TMM is probably more familiar to most individuals, as we’re well aware of the uncomfortable gastrointestinal symptoms that may be precipitated by a course of oral antibiotics, which can have profound effects on the “bugs in your gut”.

In their IJT article, the authors provide a comprehensive list of biotransformation processes and drug toxicities that are affected by these biotransformation reactions. An example presented for MMT was that deacetylation by gut microbial enzymes of phenacetin, an analgesic drug that is now banned in the US, can form a metabolite that induces methemoglobinemia. In terms of TMM, the authors cite a study suggesting that the shilimate pathway, which is the target of the herbicide active ingredient glyphosate (a “week killer”), is also inhibited in bacteria, causing changes in the gut microbial composition in rats. The alteration in microbial composition was then associated with adverse outcomes such as depression- and anxiety-related behavior.

Altogether, Koontz and coauthors summarize a very large body of literature and nicely open the readers’ eyes to potential effects of chemicals on our microbiome and our microbiome on chemicals.“

Article details

The Role of the Human Microbiome in Chemical Toxicity
Jason M. Koontz, Blair C. R. Dancy, Cassandra L. Horton, Jonathan D. Stallings, Valerie T. DiVito, John A. Lewis,
First Published June 20, 2019 Review Article
DOI: 10.1177/1091581819849833
From International Journal of Toxicology

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