THIRD WORLD NETWORK BIOSAFETY INFORMATION SERVICE
Dear Friends and Colleagues
Glyphosate and Roundup Disrupt Gut Microbiome and Blood Chemistry in Rats
Glyphosate is the world’s most widely used herbicide, and its use has accelerated with the advent of GM herbicide-tolerant crops. A new study (Item 1) is the first to describe a mechanism by which glyphosate and Roundup affect the function of the gut microbiome (bacterial populations and biochemical function) in rats. The study found that glyphosate disrupts the rat gut microbiome through the same route by which it kills weeds – inhibition of the shikimate biochemical pathway – even at low doses that regulators claim to be safe (Item 2). Although humans and animals do not have the shikimate pathway, some strains of gut bacteria do. Imbalances in gut bacteria have been linked to an ever-growing array of diseases.
In the study, glyphosate and Roundup doses were delivered through the drinking water provided to the animals at levels representing the acceptable daily intakes considered safe by European and U.S. regulators (Item 3). All the doses tested were found to cause adverse effects but stronger effects were seen with Roundup than from glyphosate. The Roundup formulation tested (MON 52276, marketed as Roundup BioFlow) was found to be more disruptive than glyphosate alone. Rats consuming this Roundup formulation developed signs of oxidative (reactive oxygen) stress in their blood, which was not as evident with glyphosate alone. This is a concern as oxidative stress can not only damage cells and organs, but also DNA, which can lead to serious disease such as cancer.
The study was able to reveal these adverse effects even over the relatively short exposure period of 90 days because the researchers used cutting-edge molecular analytical techniques known as “omics” to measure the composition of the blood and contents of the gut. These techniques are more sensitive than the standard toxicity tests performed by industry to support regulatory approvals of pesticides. As such, the study calls into question the adequacy of existing standard toxicity tests and regulatory safety limits for glyphosate intake.
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Item 1
USE OF SHOTGUN METAGENOMICS AND METABOLOMICS TO EVALUATE THE IMPACT OF GLYPHOSATE OR ROUNDUP MON 52276 ON THE GUT MICROBIOTA AND SERUM METABOLOME OF SPRAGUE-DAWLEY RATS
Robin Mesnage et al.
Environmental Health Perspectives Vol. 129 No. 1
27 January 2021
https://doi.org/10.1289/EHP6990
https://ehp.niehs.nih.gov/doi/10.1289/EHP6990
ABSTRACT
Background:
There is intense debate on whether glyphosate can inhibit the shikimate pathway of gastrointestinal microorganisms, with potential health implications.
Objectives:
We tested whether glyphosate or its representative EU herbicide formulation Roundup MON 52276 affects the rat gut microbiome.
Methods:
We combined cecal microbiome shotgun metagenomics with serum and cecum metabolomics to assess the effects of glyphosate [0.5, 50, 175mg/kg body weight (BW) per day] or MON 52276 at the same glyphosate-equivalent doses, in a 90-d toxicity test in rats.
Results:
Glyphosate and MON 52276 treatment resulted in ceca accumulation of shikimic acid and 3-dehydroshikimic acid, suggesting inhibition of 5-enolpyruvylshikimate-3-phosphate synthase of the shikimate pathway in the gut microbiome. Cysteinylglycine, γ-glutamylglutamine, and valylglycine levels were elevated in the cecal microbiome following glyphosate and MON 52276 treatments. Altered cecum metabolites were not differentially expressed in serum, suggesting that the glyphosate and MON 52276 impact on gut microbial metabolism had limited consequences on physiological biochemistry. Serum metabolites differentially expressed with glyphosate treatment were associated with nicotinamide, branched-chain amino acid, methionine, cysteine, and taurine metabolism, indicative of a response to oxidative stress. MON 52276 had similar, but more pronounced, effects than glyphosate on the serum metabolome. Shotgun metagenomics of the cecum showed that treatment with glyphosate and MON 52276 resulted in higher levels of Eggerthella spp., Shinella zoogleoides, Acinetobacter johnsonii, and Akkermansia muciniphila. Shinella zoogleoides was higher only with MON 52276 exposure. In vitro culture assays with Lacticaseibacillus rhamnosus strains showed that Roundup GT plus inhibited growth at concentrations at which MON 52276 and glyphosate had no effect.
Discussion:
Our study highlights the power of multi-omics approaches to investigate the toxic effects of pesticides. Multi-omics revealed that glyphosate and MON 52276 inhibited the shikimate pathway in the rat gut microbiome. Our findings could be used to develop biomarkers for epidemiological studies aimed at evaluating the effects of glyphosate herbicides on humans.
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Item 2
GLYPHOSATE AND ROUNDUP DISTURB GUT MICROBIOME AND BLOOD BIOCHEMISTRY AT DOSES THAT REGULATORS CLAIM TO BE SAFE
GM Watch
27 Jan 2021
www.gmwatch.org/en/news/latest-news/19677
Glyphosate and the glyphosate-based herbicide Roundup disrupt the gut microbiome by the same mechanism by which the chemical acts as a weedkiller, and these effects happen even at low doses that regulators claim to be safe, a newly published study has found.[1]
The new study was conducted by an international team of scientists based in London, France, Italy, and the Netherlands, led by Dr Michael Antoniou of King’s College London. It is published today in the journal Environmental Health Perspectives.
The study is the first to describe a mechanism by which glyphosate and Roundup affect the function of the gut microbiome (bacterial populations and biochemical function) in rats, which are the standard model that regulators use for assessing the human health risks of chemicals. The study found that glyphosate disrupts the rat gut microbiome through the same route by which it kills weeds – inhibition of the shikimate biochemical pathway.
Humans and animals do not have the shikimate pathway, enabling industry and regulators to claim that glyphosate is nontoxic to humans.[2] However, some strains of gut bacteria do have this pathway, leading the researchers on the new study to investigate whether Roundup and glyphosate could affect the gut microbiome. Imbalances in gut bacteria have been linked to an ever-growing array of diseases, including cancer, type 2 diabetes, obesity, and depression.
The researchers found that both Roundup and glyphosate affected the microbiome at all doses tested, causing shifts in bacterial populations.
Moreover, by measuring molecular composition profiles in the blood and gut, the new study also showed that the Roundup formulation tested (MON 52276, marketed as Roundup BioFlow) was more disruptive than glyphosate alone. Rats consuming this Roundup formulation developed signs of oxidative (reactive oxygen) stress in their blood, which was not as evident with glyphosate alone.
This is a concern as oxidative stress can not only damage cells and organs, but also DNA, which can lead to serious disease such as cancer.
“Safe” doses not safe after all
In the study, glyphosate and Roundup (at the same glyphosate-equivalent dose) were fed to the rats in their drinking water to give a daily intake of 0.5 mg/kg, 50 mg/kg and 175 mg/kg of 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 ADI is the dose that regulators judge safe to ingest on a daily basis over a lifetime and the NOAEL is the dose that is claimed to show no visible adverse effects in industry tests submitted to regulators.
The study reveals those assumptions to be unreliable, in that the doses tested were found to cause adverse effects. Some of these effects were found at all doses, though in general, stronger effects were seen with Roundup than from glyphosate, especially on the blood.
Importance of “omics”
The study was able to reveal adverse effects even over the relatively short exposure period of 90 days because the researchers used cutting-edge molecular analytical techniques known as “omics” to measure the composition of the blood and contents of the gut.
These techniques are more sensitive than the standard toxicity tests performed by industry to support regulatory approvals of pesticides.
The standard tests have come in for criticism from scientists for being outdated and not sensitive enough to show certain types of risk, especially those related to low doses.
Lead author of the study Dr Antoniou believes that “omics” analysis can make an important contribution to chemicals risk assessments: “Our study demonstrates the need for regulators to urgently adopt these methods as part of their risk assessments in order to more accurately evaluate the toxicity of chemical pollutants and thus better protect public health. Also, the molecular composition profiles found in this study can serve as signatures to measure the effects of glyphosate and Roundup in people.”
Roundup more toxic than glyphosate alone
More severe oxidative stress responses were found from exposure to the Roundup formulation than to glyphosate alone. However, pesticide regulators worldwide only look at the long-term toxicity of glyphosate in isolation rather than the toxicity of the formulated products.
Dr Antoniou says this approach fails to protect health and the environment: “Our results highlight the importance of investigating the long-term toxicity not just of glyphosate alone, but also the chemical mixtures that make up commercial Roundup formulations, to which we are all exposed.”
Protecting ourselves
While we wait for regulators to embrace up-to-date science, is there anything that we can all do to protect ourselves? Dr Antoniou says, “Our study calls into question the regulatory safety limits for glyphosate intake. So while that question remains, people should avoid exposure to glyphosate weedkiller and other pesticides as much as possible. This means eating organic and avoiding using pesticides in our gardens. This is a sensible precautionary approach to safeguard our own and our loved ones’ well-being.”
Notes
1. Mesnage R, Teixeira M, Mandrioli D, Falcioni L, Ducarmon QR, Zwittink RD, Mazzacuva F, Caldwell A, Halket J, Amiel C, Panoff J-M, Belpoggi F, Antoniou MN (2021) Use of shotgun metagenomics and metabolomics to evaluate the impact of glyphosate or Roundup MON 52276 on the gut microbiota and serum metabolome of Sprague-Dawley rats. Environmental Health Perspectives. https://ehp.niehs.nih.gov/doi/full/10.1289/EHP6990
2. In the Final addendum to the Renewal Assessment Report on glyphosate (October 2015), p23, rapporteur Member State Germany and co-rapporteur Member State Slovakia state, based on industry claims, “Action at the shikimic acid pathway is unique to glyphosate and the absence of this pathway in animals is an important factor of its low vertebrate toxicity.”
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Item 3
NEW STUDY FINDS GLYPHOSATE-RELATED ALTERATIONS IN GUT MICROBIOME
Carey Gillam
U.S. Right to Know
27 Jan 2021
https://usrtk.org/pesticides/new-study-finds-glyphosate-related-alterations-in-gut-microbiome/
A new animal study by a group of European researchers has found that low levels of the weed killing chemical glyphosate and the glyphosate-based Roundup product can alter the composition of the gut microbiome in ways that may be linked to adverse health outcomes.
The paper, published Wednesday in the journal Environmental Health Perspectives, is authored by 13 researchers, including study lead Dr. Michael Antoniou, head of the Gene Expression and Therapy Group within the Department of Medical and Molecular Genetics at King’s College in London, and Dr. Robin Mesnage, a research associate in computational toxicology within the same group. Scientists from the Ramazzini Institute in Bologna, Italy, participated in the study as did scientists from France and the Netherlands.
The effects of glyphosate on the gut microbiome were found to be caused by the same mechanism of action by which glyphosate acts to kill weeds and other plants, the researchers said.
The microbes in the human gut include a variety of bacteria and fungi that impact immune functions and other important processes, and a disruption of that system can contribute to a range of diseases, the researchers said.
“Both the glyphosate and the Roundup did have an effect on gut bacterial population composition,” Antoniou said in an interview. “We know that our gut is inhabited by thousands of different types of bacteria and a balance in their composition, and more important in their function, is crucial for our health. So anything that disturbs, negatively disturbs, the gut microbiome… has the potential of causing ill health because we go from balanced functioning that is conducive to health to imbalanced functioning that may lead to a whole spectrum of different diseases.”
The authors of the new paper said they determined that, contrary to some assertions by critics of glyphosate use, glyphosate did not act as an antibiotic, killing off necessary bacteria in the gut.
Instead, they found – for the first time, they said – that the pesticide interfered in a potentially worrisome way with the shikimate biochemical pathway of the gut bacteria of the animals used in the experiment. That interference was highlighted by changes in specific substances in the gut. Analysis of gut and blood biochemistry revealed evidence that the animals were under oxidative stress, a condition associated with DNA damage and cancer.
The researchers said it was not clear if the disturbance within the gut microbiome influenced the metabolic stress.
The indication of oxidative stress was more pronounced in experiments using a glyphosate-based herbicide called Roundup BioFlow, a product of Monsanto owner Bayer AG, the scientists said.
The study authors said they were conducting more studies to try to decipher if the oxidative stress they observed was also damaging DNA, which would raise the risk of cancer.
The authors said more research is needed to truly understand the health implications of glyphosate inhibition of the shikimate pathway and other metabolic disturbances in the gut microbiome and blood but the early findings could be used in the development of bio-markers for epidemiological studies and to understand if glyphosate herbicides can have biological effects in people.
In the study, female rats were given glyphosate and the Roundup product. The doses were delivered through the drinking water provided to the animals and were given at levels representing the acceptable daily intakes considered safe by European and U.S. regulators.
Antoniou said the study results build on other research that makes it clear regulators are relying on outdated methods when determining what constitutes “safe” levels of glyphosate and other pesticides in food and water. Residues of pesticides used in agriculture are commonly found in a range of regularly consumed foods.
“Regulators need to come into the twenty-first century, stop dragging their feet… and embrace the types of analyses that we have done in this study,” Antoniou said. He said molecular profiling, part of a branch of science known as “OMICS,” is revolutionizing the base of knowledge about the impacts chemical exposures have on health.
The rat study is but the latest in a series of scientific experiments aimed at determining if glyphosate and glyphosate-based herbicides – including Roundup – can be harmful to humans, even at levels of exposure regulators assert are safe.
Several such studies have found an array of concerns, including one published in November by researchers from the University of Turku in Finland who said that they were able to determine, in a “conservative estimate,” that approximately 54 percent of species in the core of the human gut microbiome are “potentially sensitive” to glyphosate.
As researchers increasingly look to understand the human microbiome and the role it plays in our health, questions about potential glyphosate impacts on the gut microbiome have been the subject not only of debate in scientific circles, but also of litigation.
Last year, Bayer agreed to pay $39.5 million to settle claims that Monsanto ran misleading advertisements asserting glyphosate only effected an enzyme in plants and could not similarly impact pets and people. The plaintiffs in the case alleged glyphosate targeted an enzyme found in humans and animals that bolsters the immune system, digestion and brain function.
Bayer, which inherited Monsanto’s glyphosate-based herbicide brand and its glyphosate-tolerant genetically engineered seed portfolio when it bought the company in 2018, maintains that an abundance of scientific study over decades confirms that glyphosate does not cause cancer. The U.S. Environmental Protection Agency and many other international regulatory bodies also do not consider glyphosate products to be carcinogenic.
But the World Health Organization’s International Agency for Research on Cancer in 2015 said a review of scientific research found ample evidence that glyphosate is a probable human carcinogen.
Since that time, Bayer has lost three out of three trials brought by people who blame their cancers on exposure to Monsanto’s herbicides, and Bayer last year said it would pay roughly $11 billion to settle more than 100,000 similar claims.