Organophosphates: Yet Another Environmental Toxin that Adversely Affects the Gut Biome and Health

Another popular request, courtesy of the survey I ran a couple of weeks ago, was for more information on how environmental toxins may affect the human biome.  I wrote about the herbicide, glyphosate (that’s found in Roundup), several months ago, and while the role that plays in human health and disease is still controversial (although less so every day), that is not the case of organophosphates (OPs), which are a family of insecticides, still commonly used in agriculture. They were also used in household products in the USA (including flea and tick collars for animals!), until the Environmental Protection Agency (EPA) banned them in 2001.  However, these chemicals are also still permitted to be used in the USA to combat mosquitoes in public areas. I am not sure about the laws concerning these chemicals in other countries.

So while the EPA recognized that the chronic exposure of these chemicals was extraordinarily toxic, especially to children, even today, “With the emergence of West Nile virus in the northeastern Unites States, programs of spraying have been implemented in large urban areas, in particular New York’s Central Park.”[i]

(Apparently, because no children play there. (Yes, I usually do try to refrain from editorializing but sometimes I can’t help it.  I am only human.))

The health effects and mechanism of action of heavy exposure to these chemicals is pretty well understood, and has to do with the alteration of the acetylcholine system in the body.  However, the health effects, and mechanism of action, of chronic low–level exposure is not.  The belief is growing that the detrimental effects of OP exposure are via the bacterial microbiome.[ii]

Because these chemicals are still in widespread use in agriculture, they easily make their way into our food and water supply at low levels:  “Consumption of these compounds affects several central nervous system functions,” as well as causing “… neonatal developmental abnormalities, endocrine disruption, neurodegeneration, neuroinflammation and cancer.  In addition, neurobehavioral and emotional deficits following OP exposure have been reported.”   That these chemicals are extraordinarily toxic is not actually controversial.  In fact, included in this family is the nerve gas, sarin. Heavy exposure can cause death.

As mentioned above, high-level, acute exposure causes an increase of the chemical messenger, acetylcholine, at the nerve synapses and neuromuscular junctions, leading to an overstimulation of the nerves and muscles.  This, in turn, leads to autonomic dysfunction (sweating, hyper salivation, diarrhea, etc.) and weakness, twitching, respiratory failure, convulsions, and possibly coma and death.

Chronic low level exposure is currently the subject of much research.  Various symptoms have been documented in both adults and children:  a more extensive list includes neurobehavioral problems (including executive functioning issues, working and visual memory, etc.), developmental neurotoxicity, cognitive changes, attention issues, anxiety, and learning problems.  Also seen are respiratory problems, metabolic issues (like obesity and diabetes), and neurodegenerative diseases like Alzheimer’s and Parkinson’s.  Animal studies indicate that exposure at levels too low to cause acetylcholine issues also appear toxic.  And this has led to great interest and investigation by the scientific community.

As I said earlier, the current thinking is that this effect is the result of OPs altering the gut bacteria, and evidence for this hypothesis is rapidly mounting:  “Emerging scientific evidence links gut microbiota dysbiosis with exposure to environmental agents such as OPs.”  One OP, chlorpyrifos (CPF), is the best studied.  Researchers find (in animal studies) that 99% of CPF is absorbed by the small intestine, and also, that it significantly alters the bacteria of the gut, lowering levels of Proteobacteria and increasing the proportions of Firmicutes and Lactobacillales.  Scientists have also found that, “…chronic CPF-exposure during critical pre- and postnatal periods causes morphological changes in the intestinal epithelium and increases intestinal permeability…”  That is, it causes leaky gut. In rats, it’s been shown to alter the pups’ microbiota, including increasing the abundance of Clostridium…and you’ve read many times on this blog (here’s just one example) about the detrimental effects of excessive propionic acid, the short-chain fatty acid produced by Clostridium.  “Collectively, these data suggest that prenatal and lactational exposure to CPF have both short-term and long-lasting impacts on the microbiota, indicating that exposure in infancy should be avoided.”

While studies into the microbiome effects of other OPs are scarce, what we do have indicates that they too have adverse effects.  For example, in mice, the OP, malathion, greatly altered the gut biome, including increasing Clostridum.

These authors conclude that, “The research above shows that several Ops, such as CPF, caused dysbiosis both in childhood and adulthood…Therefore, gut  microbiota dysbiosis should be taken into consideration when evaluating the neurotoxicity of these compounds.”

There is limited evidence to date of ways to manipulate the gut bacteria to alleviate the effects of exposure to OPs. However, the prebiotic, inulin, has shown some promise. In one rat study, in which the animals were exposed to CPF, those who also received inulin showed less loss of biome diversity and less loss of SCFA production.  In an in vitro model, “…the dysbiosis and metabolic imbalance in the intestinal environment observed after CPF exposure could be prevented by co-treatment with inulin.”

Probiotics have also shown some good initial results.  Lactobacillus bacteria bind to OPs and reduce intestinal absorption, in vitro.  In an animal model (Drosophila, which are fruit flies commonly used in scientific studies), pre-treating with Lactobacillus rhamnosus reduced mortality and growth deficits.

So to summarize, it appears that avoiding exposure to these chemicals is key…but since it appears we may not be able to fully do so, once again, protecting our gut bacteria via the intake of pre- and possibly probiotics may be helpful.  As I always say to you at the conclusions of these kinds of post – I’ll keep an eye out for any new developments!

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[i] https://emedicine.medscape.com/article/1175139-overview

[ii] Roman, P, Cardona, D, Sempere, L, Carvajal, F. Microbiota and organophasphates. NeuroToxicology. 2019;75:200-208.   doi: 10.1016/j.neuro.2019.09.013.