As these GEITP pages continue to emphasize, a trait (phenotype; e.g. height, weight, green eyes, blood pressure, a disease such as schizophrenia or obesity, adverse response to a drug) reflects the contribution of: genetics (DNA sequence differences in genes), epigenetic effects (DNA-sequence independent RNA-interference, DNA-methylation, histone modifications, chromatin remodeling), environmental factors (e.g. diet, lifestyle, smoking history), endogenous influences (e.g. cardiopulmonary or kidney disease), and each person’s unique microbiome. This comprehensive review [attached] updates some of the massive literature on the interaction of environmental factors and the microbiome.
Authors state that humans are exposed to hundreds of chemicals — as evidenced by the fact that more than 300 environmental chemicals and/or their metabolites have been measured in human biological samples. Human exposure to these environmental chemicals is constant, and some of these chemicals have long half-lives in the body and environment. Chemicals such as bisphenols, phthalates, pesticides, persistent organic pollutants (POPs; e.g. polychlorinated biphenyls, polycyclic aromatic hydrocarbons, dioxins), and heavy metals (e.g. lead, mercury, arsenic) have endocrine-disrupting effects that can alter hormonal metabolism. Many of these environmental chemicals are associated with adverse health outcomes, including male and female reproductive and developmental defects, type-2 diabetes, cardiovascular disease, liver disease, obesity, thyroid disorders, and immune dysfunction. Because the gut microbiome influences host metabolism, authors suggest these parent chemicals and metabolites may mediate some of the toxic effects of environmental chemicals by way of the microbiome. With chronic exposure to a mixture of environmental chemicals, authors suggest that it is vital to understand how the gut microbial community might be altered — in response to environmental chemical exposures, and the implications of such changes on health outcomes. Reviewing the literature, authors state that the effects of the environmental chemicals on gut microbiota highly depend on sex and age.
These GEITP pages would conclude that, although it is a wide-ranging review, “importance of the dose” of chemicals is not emphasized. In other words, the fact that “more than 300 environmental chemicals have been measured in human biological samples” largely reflects the ability of new instrumentation to detect such chemicals at increasingly lower levels of concentration. Detection of a chemical in a patient — and associating that with a clinical effect — are two different things. Most of the >160 references cited are studies in various animals using large doses. As Paracelsus wrote (in 1538 AD), “Alle Dinge sind Gift, und nichts ist ohne Gift; allein die dosis machts, daß ein Ding kein Gift sei.” (“All things are poison (toxic) and there is nothing that is not toxic; it is the dose alone that makes something toxic or not toxic”). 😊
Toxicol Sci Aug 2020; 176: 253–284