Glyphosate and Roundup found to disrupt gut microbiome by inhibiting shikimate pathway

Fatty liver disease and death of liver tissue were also confirmed in rats fed regulatory permitted and thus presumed safe doses of the weedkiller.

The primary mechanism of how glyphosate herbicides kill plants is by inhibiting an enzyme called EPSPS, which is part of a biochemical pathway known as the shikimate pathway. The shikimate pathway is responsible for the synthesis of certain aromatic amino acids that are vital for the production of proteins, the building blocks of life. Thus when the synthesis of the aromatic amino acids is blocked by glyphosate inhibition of EPSPS, the plant dies.

Humans and animals do not have the shikimate pathway, so industry and regulators have claimed that glyphosate is nontoxic to humans.[1] However, some strains of gut bacteria do have the shikimate pathway, leading to much debate about whether Roundup and glyphosate could affect the gut microbiome (bacterial populations). Imbalances in gut bacteria have been found to be linked with many diseases, including cancer, type 2 diabetes, obesity, and depression.

As many species of gut bacteria do have the shikimate pathway, scientists have hypothesised that glyphosate herbicides could inhibit the EPSPS enzyme of the shikimate pathway in these organisms, leading to imbalance in the microbiome, with potentially negative health consequences. Some have proposed that if glyphosate herbicides do disrupt the gut microbiome, EPSPS inhibition will be the primary mechanism through which this occurs.

However, proof that glyphosate herbicides can inhibit the EPSPS enzyme and the shikimate pathway in gut bacteria has been lacking. But a new study has proven beyond doubt that this does indeed happen.

The study in rats by an international team of scientists based in London, France, Italy, and the Netherlands, led by Dr Michael Antoniou of King’s College London and posted on the pre-peer-review site BioRxiv, has found that Roundup herbicide and its active ingredient glyphosate cause a dramatic increase in the levels of two substances, shikimic acid and 3-dehydroshikimic acid, in the gut, which are a direct indication that the EPSPS enzyme of the shikimic acid pathway has been severely inhibited.

In addition, the researchers found that both Roundup and glyphosate affected the microbiome at all dose levels tested, causing shifts in bacterial populations.

Levels tested were previously assumed to have no adverse effect

For the study, female rats (12 per group) were fed a daily dose of either glyphosate or a Roundup formulation approved in Europe, called MON 52276. Glyphosate and Roundup were administered via drinking water to give a glyphosate daily intake of 0.5 mg, 50 mg and 175 mg/kg body weight per day (mg/kg bw/day), which respectively represent the EU acceptable daily intake (ADI), the EU no-observed adverse effect level (NOAEL), and the US NOAEL.

The study found certain adverse effects at all doses tested, disproving regulators’ assumptions that these levels have no adverse effect…..

The researchers also saw other changes in the gut metabolome that were indicative of oxidative stress, a type of imbalance that can lead to mutations in DNA, damage to cells and tissues, and diseases such as cancer. Gut bacteria respond to oxidative stress by producing certain substances that combat it.[2]…

The study also revealed that Roundup, and to a lesser extent glyphosate, damaged the liver and kidneys of the rats, even over the relatively short study period of 90 days. Histopathological (microscopic) examination of the liver showed that the two higher doses of Roundup caused a statistically significant and dose-dependent increase in lesions, fatty liver disease changes, and necrosis (death of tissue)….

The fatty liver disease findings confirm and extend the observations of an earlier study from Dr Antoniou’s team. In this previous study, rats were given a dose of Roundup that was a staggering 125,000 times lower, based on the dose of glyphosate, than the lowest dose group in the new investigation. However, they were fed this dose over a longer-term period of two years. This lower dose also caused fatty liver disease. “We now know that a lower dose of Roundup over a longer time or a higher dose over a shorter time produce the same outcome,” said Dr Antoniou….

There were clear increases in kidney dysfunction – lesions, mineralisation and necrosis – in the Roundup and glyphosate groups, but they were mostly not statistically significant. This again may be because there were too few animals or the study was too short. Anyone wishing to replicate these effects in other studies should extend the length of the study and use larger numbers of animals to see if serious harm to the kidneys occurs over the long term….

https://www.gmwatch.org/en/news/latest-news/19261-glyphosate-and-roundup-proven-to-disrupt-gut-microbiome-by-inhibiting-shikimate-pathway

Roundup Killing Kidneys in Central America, India, Sri Lanka

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