In environmental and occupational health we are accustomed to thinking about target organs for toxic exposures. We are concerned with effects on the lungs, kidney, and liver. We seldom think of the gastrointestinal tract because although it is subject to effects from ingesting foodborne hazards it is more often a route of entry than a target organ. Our perception has been that the “GI tract” and what is in it is a secondary issue, not front and center in environmental and occupational toxicology.
But is that really true? Our perception is based on ignorance, not evidence.Citation1,Citation2
Within the GI tract is a commensal universe, a highly structured microbial community which we only dimly understand. We are aware of its size (on the order of 100 trillion individual bacteria compared to about 75 trillion human body cells in its host), its mass (about 2 kg), its diversity (bacteria, viruses, bacteriophages, archaea, even the occasional eukaryote), and its information content (2 × 106 microbial genes compared to 10 × 104 human genes in the organism that is its host), and that the flora changes with illness, medication, and in new environments.
We know all these things with the certainty of someone watching from above a crowd forming on the street to watch a parade, with no idea where these people are coming from or where they are going, just specks on the street seemingly bystanders to what is passing them by. Until now, we have not thought to ask what the crowd is doing, what they are yelling, what they are snacking on, whether they are sitting in the sun or the shade, and what they will be doing when the parade is over.
We have only the dimmest idea of how the microbial biome varies along the gut and where the action takes place, because what we know is either based on fecal flora or what we have learned in disease. We also know that taking the direct approach to manipulating the gut flora, by fecal transplant (ingesting a capsule with a donor’s fecal flora) can be dangerous, as demonstrated by the death of an immunocompromised patient when one strain of Escherichia coli in the sample carried an antibiotic-resistance gene.Citation3 We know that there is some complex interplay between the microbial biome and immune function, built on colonization from the mother’s birth canal during birth.
But isn’t it a stretch to think that environmental and occupational hazards play a significant role in altering the gut microbiome? We need to find out but it is not a stretch that this may be an unappreciated target organ.
The route of exposure of most obvious concern is clearly oral and there are an abundance of ways that a food or water contaminant, a food additive or residue, or an inhaled and aspirated material might reach and affect the gut microbiome. Of course, they would have to get through the stomach and its acidity first. The stomach is normally almost sterile (in adults), except in serious disease and Helicobacter pylori infection. Once beyond the pylorus, however, there is little to impede further growth and the reservoir for the microbiome appears to be the cecum, a sac at the transition from the small intestine to the colon, where the appendix lies. Many xenobiotics are metabolized in the liver and excreted in bile, both organic compounds and metals. Many of these are of toxicological interest, such as organochlorine compounds and mercury. Iron, important in the inflammatory response, has long been known to be concentrated in bile.Citation4 The common bile duct carries the secreted bile to the duodenum, the first part of the small intestine, just downstream from this transition. At this point, xenobiotics concentrated from the circulation meet the microbiome by a route independent of ingestion.
The state of the art is such that microbiome research probably needs a bit more time to catch up to the question but we are learning more about our commensal passengers day by day. The potential certainly exists for an interaction between xenobiotics from ingestion or biliary excretion and the human microbiome. Would this be a big effect or nothing much? Is it an unexplored pathophysiological mechanism or a small detail? We will have no idea until we look.
At the same time, we need to exercise discretion in talking about the possibility. We have seen the abuse and harm that has been done resulting from theorizing without empirical validation in the false and dishearteningly invalid theories of autism based on such speculation. [References omitted by intent.] Hypotheses like this need to be tested in the laboratory or clinic before there is further discussion, not on social media.
We look forward to the first paper with evidence one way or the other.
Editor Emeritus
Archives of Environmental and Occupational Health[email protected]
References
- Usell LK, Metcalf JL, Parfrey LW, Knicght R. Defining the human microbiome. Nutr Rev.2012;70(Suppl 1):S38–S44. doi:10.1111/j.1753-4887.2012.00493.x.
- Lloyd-Price J, Abu-Ali G, Huttenhower C. The healthy human microbiome. Genome Med. 2016;8(1):51. Available at: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4848870/. Accessed 2 July 2019. doi:10.1186/s13073-016-0307-y.
- Soucheray S. FDA issues alert after fecal microbiota transplant death. CIDRAP (Center for Infectious Disease Research and Policy, University of Minnesota), 14 June 2019. Available at: http://www.cidrap.umn.edu/news-perspective/2019/06/fda-issues-alert-after-fecal-microbiota-transplant-death. Accessed 2 July 2019.
- Ishihara N, Matsushiro T. Biliary and urinary excretion of metals in humans. Arch Environ Health. 1986;41(5):324–330. doi:10.1080/00039896.1986.9936705.
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