The Ramazzini Institute 13-week pilot study on glyphosate and Roundup administered at human-equivalent dose to Sprague Dawley rats: effects on the microbiome

Abstract

BackgroundGlyphosate-based herbicides (GBHs) are broad-spectrum herbicides that act on the shikimate pathway in bacteria, fungi, and plants. The possible effects of GBHs on human health are the subject of an intense public debate for both its potential carcinogenic and non-carcinogenic effects, including its effects on microbiome. The present pilot study examines whether exposure to GBHs at doses of glyphosate considered to be “safe” (the US Acceptable Daily Intake - ADI - of 1.75 mg/kg bw/day), starting from in utero, may modify the composition of gut microbiome in Sprague Dawley (SD) rats.MethodsGlyphosate alone and Roundup, a commercial brand of GBHs, were administered in drinking water at doses comparable to the US glyphosate ADI (1.75 mg/kg bw/day) to F0 dams starting from the gestational day (GD) 6 up to postnatal day (PND) 125. Animal feces were collected at multiple time points from both F0 dams and F1 pups. The gut microbiota of 433 fecal samples were profiled at V3-V4 region of 16S ribosomal RNA gene and further taxonomically assigned and assessed for diversity analysis. We tested the effect of exposure on overall microbiome diversity using PERMANOVA and on individual taxa by LEfSe analysis.ResultsMicrobiome profiling revealed that low-dose exposure to Roundup and glyphosate resulted in significant and distinctive changes in overall bacterial composition in F1 pups only. Specifically, at PND31, corresponding to pre-pubertal age in humans, relative abundance for Bacteriodetes (Prevotella) was increased while the Firmicutes (Lactobacillus) was reduced in both Roundup and glyphosate exposed F1 pups compared to controls.ConclusionsThis study provides initial evidence that exposures to commonly used GBHs, at doses considered safe, are capable of modifying the gut microbiota in early development, particularly before the onset of puberty. These findings warrant future studies on potential health effects of GBHs in early development such as childhood.Electronic supplementary materialThe online version of this article (10.1186/s12940-018-0394-x) contains supplementary material, which is available to authorized users.

Glyphosate and glyphosate‐based herbicide exposure during the peripartum period affects maternal brain plasticity, maternal behaviour and microbiome

“…Although the precise role of each of these bacteria phyla for brain physiology is, to our knowledge, far from understood, a few studies have suggested that a dysregulation of Bacteroidetes or Firmicutes populations is associated with mental health disorders, including autism and Alzheimer's disease . To support our findings, other studies conducted not only in rats, but also in bees, report similar changes in Bacteroidetes and/or Firmicutes following Glyphosate or Glyphosate‐based herbicide exposure . Similarly, the population of the genera Alloprevotella is increased in the present study, whereas other studies have found an association between Parkinson and Alzheimer's disease and a reduced population of the family of Prevotellaceae .…”

“…132,133 To support our findings, other studies conducted not only in rats, but also in bees, report similar changes in Bacteroidetes and/ or Firmicutes following Glyphosate or Glyphosate-based herbicide exposure. 40,48,127,128 Similarly, the population of the genera Alloprevotella is increased in the present study, whereas other studies have found an association between Parkinson and Alzheimer's disease and a reduced population of the family of Prevotellaceae. [134][135][136][137] It is obviously important to note that these studies are only correlational and the precise consequences of the 69 revealed that low (5 mg kg -1 ), medium (50 mg kg -1 ) or high doses (500 mg kg -1 ) of Glyphosate altered levels of Zn 2+ and Fe 2+ in the liver, spleen and kidney in a dose dependent-way in adult male rat.…”

“…The effect of glyphosate or glyphosate based herbicide on bacterial population is not completely unexpected. A few studies, not only mostly on soil bacteria, but also in animal species, from insects to reptiles and mammals, have investigated the effect of the pesticide on microorganism ecology. Although the precise role of each of these bacteria phyla for brain physiology is, to our knowledge, far from understood, a few studies have suggested that a dysregulation of Bacteroidetes or Firmicutes populations is associated with mental health disorders, including autism and Alzheimer's disease .…”

Quantification of glyphosate and aminomethylphosphonic acid from microbiome reactor fluids

“…A recent study showed that glyphosate affects honey bees by altering their microbial community composition, and this may be a threat to bee health due to a greater susceptibility to pathogens . For the mammalian microbiome, Lozano et al found a gender‐specific effect on the composition of intestinal microbiota in rats and Mao et al revealed effects in rats on the bacterial composition in the F1 generation …”

“…9 For the mammalian microbiome, Lozano et al found a gender-specific effect on the composition of intestinal microbiota in rats 10 and Mao et al revealed effects in rats on the bacterial composition in the F1 generation. 11 Apart from the inhibitory effect of glyphosate on EPSPS, some microorganisms are able to metabolize glyphosate. The first biodegradation route relies on the cleavage of the C&bond;P bond by carbon-phosphorus lyase, resulting in sarcosine and inorganic phosphorus.…”