Living with a Microbiome: Role of Toxic Exposures in Shaping “The Completed Self”

“The Completed Self” model for formation of the human-microbial superorganism in early life posits that: 1) symbiotic self completion is a critical step in the developmental programming of later-life health vs. disease, 2) the immune definition of self includes our internal microbial ecosystem, and 3) commensal-driven host metabolism and immune maturation are critical factors in subsequent tissue homeostasis. A consideration of humans as beyond-mammalian would be likely to alter our prevailing views of toxicity, health hazards, and preventive measures as well as the tools we employ for effective safety assessment. Commensal microbes of the skin, oral cavity, airways, gut and urogenital tract effectively connect us to our external environment and are on the front line of environmental exposures via the inhalation, oral and dermal routes. The composition of these microbes and their capacity: 1) to handle, sequester, exclude and metabolize specific dietary factors and xenobiotics and, also, 2) to direct developing immune and other host cells in their maturation and environmental responses are critical in programming later-life health vs. disease.  Prenatal, postnatal and even transgenerational epigenetic factors have the capacity to either support or interfere with the establishment of the microbiome and/or immune-microbiome interactions.  Lack of self completion appears to be an important route to metabolic disorders, immune dysfunction, misregulated inflammation, tissue pathologies and both non-communicable and infectious diseases. Environmental risk factors (e.g., environmental chemicals, drugs, diet, physical and lifestyle factors) during development are considered in light of the goals of self completion in the child and a fully-developed immune system to support the newly-formed, human-microbial symbiont.