Glyphosate and the Gut Microbiome

1. Glyphosate and Glycine

Contrary to the hypothesis that glyphosate destroys glycine or substitutes for it in human proteins, rigorous scientific evidence confirms that glyphosate does not incorporate into polypeptide chains. 

• No Protein Substitution: A definitive 2019 proteomics study on actively dividing mammalian cells found no direct evidence that glyphosate replaces glycine during protein synthesis. Statistical analysis of global proteome changes revealed that all candidate peptides suggesting substitution were false discoveries.
  • Source: Antoniou et al. (2019). “Glyphosate does not substitute for glycine in proteins of actively dividing mammalian cells.” BMC Research Notes.
• Metabolic Breakdown: Rather than being destroyed, glyphosate is metabolized by environmental microbes into aminomethylphosphonic acid (AMPA) and glycine, effectively releasing glycine rather than consuming it.
• Competitive Inhibition: While glyphosate is a structural analogue of glycine, its primary risk regarding glycine homeostasis lies in potential competitive inhibition for absorption or enzyme binding, not chemical destruction or protein misfolding. 

2. Effects on Plant Glycine and Metabolism

Glyphosate does not directly target glycine in plants but causes indirect metabolic disruption through the inhibition of the shikimate pathway. 

• Primary Mechanism (EPSPS Inhibition): Glyphosate specifically inhibits the enzyme 5-enolpyruvylshikimate-3-phosphate synthase (EPSPS).  This blocks the synthesis of aromatic amino acids (tryptophan, tyrosine, phenylalanine) and causes a toxic accumulation of shikimic acid.
  • Source: Amrhein et al. (1980). “The Site of the Inhibition of the Shikimate Pathway by Glyphosate.” Plant Physiology.
• Indirect Glycine Suppression: The resulting metabolic imbalance depletes phosphoenolpyruvate (PEP), a carbon substrate required for the de novo synthesis of non-aromatic amino acids, potentially suppressing glycine production from serine.
• Microbial Degradation in Soil: In the rhizosphere, glyphosate is degraded by soil microbes into AMPA and glycine. Thus, the breakdown of the herbicide in the soil environment actually contributes glycine rather than destroying it.
  • Source: van Bruggen et al. (2018). “Indirect Effects of the Herbicide Glyphosate on Plant, Animal and Human Health Through its Effects on Microbial Communities.” Frontiers in Environmental Science. 

3. Impact on the Gut Microbiome

Glyphosate affects the gut microbiome by selectively inhibiting the shikimate pathway in susceptible bacteria, leading to dysbiosis (microbial imbalance). While human cells lack this pathway, many gut bacteria rely on it for survival. 

Selective Pressure: Beneficial vs. Pathogenic Bacteria

• Susceptible Beneficial Bacteria: Genera such as Lactobacillus, Bifidobacterium, Enterococcus, and Bacillus often possess Class I EPSPS enzymes, which are highly sensitive to glyphosate. Exposure suppresses their growth and reduces the production of short-chain fatty acids (SCFAs).
  • Source: Shehata et al. (2013). “The effect of glyphosate on potential pathogens and beneficial members of poultry microbiota in vitro.” Current Microbiology. (Cited in Mesnage et al. (2021))
• Resistant Pathogens: Opportunistic pathogens, including Clostridium species (e.g., C. botulinum, C. perfringens), Salmonella, and Escherichia coli, frequently possess Class II EPSPS enzymes or other resistance mechanisms, allowing them to overgrow when competition is removed.
  • Source: Samsel & Seneff (2013). “Glyphosate’s Suppression of Cytochrome P450 Enzymes and Amino Acid Biosynthesis by the Gut Microbiome.” Entropy. 

Metabolic Disruption and Biomarkers

• Shikimate Accumulation: Inhibition of EPSPS causes a buildup of shikimic acid and 3-dehydroshikimic acid in the gut.  This accumulation serves as a definitive biomarker that the shikimate pathway is blocked in the microbiome.
  • Source: Mesnage et al. (2021). “Use of Shotgun Metagenomics and Metabolomics to Evaluate the Impact of Glyphosate… on the Gut Microbiota.” Environmental Health Perspectives.
• Metabolite Depletion: The blockade prevents the synthesis of aromatic amino acids, potentially leading to reduced levels of tryptophan (a precursor for serotonin) and other compounds essential for host immune and neurological health. 
• Limited Degradation: The human gut microbiota has negligible capacity to degrade glyphosate into AMPA. Consequently, glyphosate passes through the gut largely unchanged, maintaining its inhibitory potential throughout the intestinal tract. 

Health Implications

The resulting dysbiosis is linked to several downstream effects observed in animal models:

• Intestinal Permeability: Loss of beneficial bacteria can compromise the gut barrier, leading to “leaky gut” and systemic inflammation. 
• Immune and Neurological Effects: Alterations in the microbiota-gut-brain axis and reduced anti-inflammatory metabolites may contribute to immune dysfunction. 
• Antibiotic Resistance: The selective pressure exerted by glyphosate may co-select for antibiotic resistance traits in surviving pathogenic bacteria.
• Loss of beneficial organisms we rely on to produce certain nutrients will lead to deficiencies in those nutrients.
• Loss of organisms responsible for digesting certain foods will lead to incomplete digestion.

We know too little about the role of our microbiomes to be able to even know the full extent of the harm that glyphosate (or any other biocide) does.