Toxicomicrobiomics: Narrowing the Gap Between Environmental and Medicinal Toxicogenomics

To the Editor:

We live in exciting times for microbiome research and diagnostic innovation in microbiology, pharmacology, and toxicology. I had the opportunity to highlight some of the emerging outlooks in this context, thanks to the OMICS editor for the thought-provoking questions in the interview published earlier this year (Aziz, 2018) about the crystallization of pharmacomicrobiomics as a distinct field of systems pharmacology. In the interview, and then during subsequent discussions with colleagues worldwide, the question emerged on the future and sequels of pharmacomicrobiomics, and how it overlaps with systems toxicology.

One of the possible developments of the systematic study of drug/microbiome interactions is the special focus on adverse drug effects, or more broadly, adverse effects of health interventions ranging from drugs and vaccines to nutrition, and how they vary between persons and populations according to the microbiome composition and metabolic capability [metabotype (Li et al., 2008)].

Precision medicine is aimed at stratifying patients to allow therapeutic innovations that are more efficacious, safer, less costly, and with fewer toxic effects. Consequently, the study of how patients are differentially susceptible to adverse effects has gained momentum, notably in anticancer drugs and drugs used for life-treating chronic diseases.

Toxicogenomics studies how human genome variations affect the metabolism of xenobiotics and the extent of drug toxicity. It emphasizes the side of toxicology in which a drug is viewed as a controlled poison used for treatment by administering at the right dose in the right clinical context. However, toxicology has a much wider scope as it deals with xenobiotics as a large group of chemicals, be they drugs, plant/food components, or simply environmental poisons/pollutants (Nuwaysir et al., 1999). Not surprisingly, depending on whether one adopts an ecological or an anthropocentric view, it could be debated whether toxicology is a branch of pharmacology or vice versa.

The two sciences, toxicology and pharmacology, certainly overlap, and the extent of their overlap is a function of the gap between ecology and medicine, between viewing humans (Homo sapiens) as distinct organisms that need to be studied in a privileged way or, alternatively, viewing the human holobiont as a supraorganism, an ecosystem of its own. Indeed, such a dichotomy has been challenged by the emergence of microbiome research (Ley et al., 2007) and is reflected in scientific communities and conferences merging environmental, medical, and biological topics under the umbrellas of biology and One Health approaches.

Thus, as the term toxicomicrobiomics emerged this year, first in OMICS (Aziz, 2018) and then in an review article (Aziz et al., 2018), it immediately triggered the question whether toxicomicrobiomics should be confined to drug adverse effects and human response to xenobiotics, or whether it should be more inclusive by studying the fate of all xenobiotics, from biotic or abiotic origins, not only in the human body but in any environment as well. Such scope is not far from the initial toxicogenomics literature at the turn of the millennium (Nuwaysir et al., 1999).

As the Earth Microbiome project is sequencing and analyzing all DNA-based entities in biotic and abiotic ecosystems, environmental toxicomicrobiomics could strongly benefit from the wealth of sequence data from every possible sample of the Earth biome. For example, the bioremediation of environmental pollutants may shed light on drug detoxification in the human body. Likewise, the biodegradation of pharmaceuticals in wastewater by microbial consortia can benefit tremendously from studies on drug metabolism by the human microbiome.

In conclusion, a specific term, toxicomicrobiomics, for the interactions between the microbiome and toxins/xenobiotics is not spurious but rather much needed. The distinction of this term from pharmacomicrobiomics will widen the scope of xenobiotics being studied, and will enrich both systems pharmacology and toxicology.