Glyphosate influences the brain, maternal behaviour and microbiota in a rat model

In active form alone, or as a component of a commercial herbicide, glyphosate ingested by rats at a dose of 5mg/kg/day intensifies the maternal licking behaviour of young and changes communication between neurons (synapses) in the hippocampus and prefrontal cortex of the mother. Modifications of the intestinal microbiota with glyphosate were also shown in this study conducted by Irset researchers (UnivRennes1/EHESP/Inserm), in collaboration with the Micalis laboratory (INRA/AgroParisTech/UPSaclay), published in the Journal of Neuroendocrinology (7 May 2019).

Photo : Th G via Pixabay
  1. Changes in maternal care and brain physiology
  2. Microbiota modifications
  3. Possible effect of additives?
  4. Reference and financing

Glyphosate is used in many pesticides and is currently the most commonly used herbicide worldwide. Its impact on health, and more particularly on the development of cancer, is the subject of intense debate among experts, but some studies suggest that this herbicide could also affect the brain and behaviour. This is what research led by the Institut de recherche en santé, environnement, travail (Irset - Université de Rennes 1/Inserm/EHESP) has just explored.

This study shows that glyphosate, either as an active ingredient alone or as a commercial herbicide, influences the brain, maternal behaviour and microbiota.
Treatment was achieved by daily ingestion, during gestation and lactation, of wafers biscuits containing 5mg glyphosate/kg (animal weight)/day, with the maximum no observed adverse effect level currently set at 50mg/kg/day.

 

Summary of the study's conclusions - Glyphosate, well known for its action on plants but also on bacteria, affects the intestinal microbiota after ingestion of herbicides present in food. A change in the natural bacterial community of the intestines could explain the observed change in the functioning of the nervous system, leading to modulation of maternal behaviour (licking). © J. Dechartres et al./SMART - © J. Dechartres et al. / SMART

 

Changes in maternal care and brain physiology

The researchers observed that maternal licking behaviour, essential for offspring development, was significantly higher among mothers treated with Roundup 3 +® compared to controls. When the brains of these animals were subsequently analysed, specific areas associated with aspects of maternal behaviour, such as the hippocampus and prefrontal cortex, showed changes in communication between neurons (synapses) compared to control animals that were not exposed to these molecules.
 
In particular, a variation in the expression of synaptophysin, a protein involved in the proper functioning of synaptic vesicles which contain neurotransmitters, showed an increase in the hippocampus (memory, emotion) and a decrease in the prefrontal cortex (decision) following exposure to glyphosate alone or in as part of the herbicide.

However, only exposure to the commercial formulation of glyphosate led to an increase in the number of late-stage new neurons in the dorsal region of the hippocampus.
 

Microbiota modifications

In collaboration with the Micalis laboratory (INRA/AgroParisTech/UPSaclay), this study shows that one of the targets of these pesticides could be the intestinal microbiota, commonly called the "intestinal flora".

Glyphosate is a molecule that specifically targets an enzyme that is not produced by animals but is found in plants... and bacteria!
Ingestion of this compound could, therefore, alter the microbiota present in the digestive system and affect the brain and behaviour. Recent work has clearly shown that an alteration of this microbiota has an impact on the brain and behaviour. For example, many studies suggest that an alteration of certain bacterial communities such as Firmicutes and Bacteroides, the most important bacteria in number and diversity in vertebrates (including humans), is linked to various disorders and pathologies such as Alzheimer's, Parkinson's, or Autism Spectrum Disorder.

What is observed in this study is that exposure to Roundup 3+ ® increases the proportion of Bateroidetes but decreases the Firmicutes. Glyphosate alone affects the number of Bytyricicoccus or Ruminoccoaceae.

It cannot be excluded that ingestion of this herbicide, whose residues are found in the daily diet, may have an impact on the microbiota and consequently may modify brain function and behaviour. The causal link is extremely complex to prove. To confirm this, it will be necessary to treat rats, isolate their microbiota, transfer it to germ free animals (which do not have their own microbiota) and study the effects of the microbiota on the brain and behaviour.
 

Bacteroides fragilis  - Bacteroides of the fragilis group (here magnified 1000 times) are an essential component of the intestinal microbiota.  - © Public Health Image Library

Possible effect of additives?

This study also showed different effects between glyphosate alone (never used alone as a herbicide product) and the commercial formulation.
 
Commercial formulations all contain a series of additional compounds, such as tallowamines, which allow glyphosate to penetrate the plant.
These molecules, as such, may have an effect on vertebrates but may also interact with glyphosate to impact the microbiota, brain physiology and/or behaviour.
It is important to note here that the long-term consequences of glyphosate exposure are not known. There is still a lot of work to be done to determine how the different glyphosate-based pesticides may impact health.
 

Reference and financing

Glyphosate and Glyphosate-based herbicide exposure during the peripartum period affects maternal brain plasticity, maternal behavior and microbiome
Dechartres J, Pawluski JL, Gueguen MM, Jablaoui A, Maguin E, Rhimi M, Charlier TD
J. Neuroendocrinol. e12731. doi: 10.1111/jne.12731.

(Special Edition "Parental Brain" of the Journal of Neuroendocrinology).
 
This work was conducted as part of Julie Dechartres' doctoral thesis and was funded by the University of Rennes 1 (doctoral scholarship and "emerging challenge").
 
Most of the popularized text of this article was written by Professor Thierry Charlier.
Translation into English by co-author Jodi Pawluski.