Ackermann et al., 2015
Ackermann, W., Coenen, M., Schrodl, W., Shehata, A. A., & Kruger, M.; “The influence of glyphosate on the microbiota and production of botulinum neurotoxin during ruminal fermentation;” Current Microbiology, 2015, 70(3), 374-382; DOI: 10.1007/s00284-014-0732-3.
ABSTRACT:
The aim of the present study is to investigate the impact of glyphosate on the microbiota and on the botulinum neurotoxin (BoNT) expression during in vitro ruminal fermentation. This study was conducted using two DAISY(II)-incubators with four ventilated incubation vessels filled with rumen fluid of a 4-year-old non-lactating Holstein-Friesian cow. Two hundred milliliter rumen fluid and 800 ml buffer solution were used with six filter bags containing 500 mg concentrated feed or crude fiber-enriched diet. Final concentrations of 0, 1, 10, and 100 microg/ml of glyphosate in the diluted rumen fluids were added and incubated under CO2-aerated conditions for 48 h. The protozoal population was analyzed microscopically and the ruminal flora was characterized using the fluorescence in situ hybridization technique. Clostridium botulinum and BoNT were quantified using most probable number and ELISA, respectively. Results showed that glyphosate had an inhibitory effect on select groups of the ruminal microbiota, but increased the population of pathogenic species. The BoNT was produced during incubation when inoculum was treated with high doses of glyphosate. In conclusion, glyphosate causes dysbiosis which favors the production of BoNT in the rumen. The global regulations restrictions for the use of glyphosate should be re-evaluated. FULL TEXT
Shehata et al., 2013
Shehata, A. A., Schrodl, W., Aldin, A. A., Hafez, H. M., & Kruger, M.; “The effect of glyphosate on potential pathogens and beneficial members of poultry microbiota in vitro;” Current Microbiology, 2013, 66(4), 350-358; DOI: 10.1007/s00284-012-0277-2.
ABSTRACT:
The use of glyphosate modifies the environment which stresses the living microorganisms. The aim of the present study was to determine the real impact of glyphosate on potential pathogens and beneficial members of poultry microbiota in vitro. The presented results evidence that the highly pathogenic bacteria as Salmonella Entritidis, Salmonella Gallinarum, Salmonella Typhimurium, Clostridium perfringens and Clostridium botulinum are highly resistant to glyphosate. However, most of beneficial bacteria as Enterococcus faecalis, Enterococcus faecium, Bacillus badius, Bifidobacterium adolescentis and Lactobacillus spp. were found to be moderate to highly susceptible. Also Campylobacter spp. were found to be susceptible to glyphosate. A reduction of beneficial bacteria in the gastrointestinal tract microbiota by ingestion of glyphosate could disturb the normal gut bacterial community. Also, the toxicity of glyphosate to the most prevalent Enterococcus spp. could be a significant predisposing factor that is associated with the increase in C. botulinum-mediated diseases by suppressing the antagonistic effect of these bacteria on clostridia. FULL TEXT
Tremlett et al, 2017
Tremlett, H., Bauer, K. C., Appel-Cresswell, S., Finlay, B. B., & Waubant, E.; “The gut microbiome in human neurological disease: A review;” Annals of Neurology, 2017, 81(3), 369-382; DOI: 10.1002/ana.24901.
ABSTRACT:
Almost half the cells and 1% of the unique genes found in our bodies are human, the rest are from microbes, predominantly bacteria, archaea, fungi, and viruses. These microorganisms collectively form the human microbiota, with most colonizing the gut. Recent technological advances, open access data libraries, and application of high-throughput sequencing have allowed these microbes to be identified and their contribution to neurological health to be examined. Emerging evidence links perturbations in the gut microbiota to neurological disease, including disease risk, activity, and progression. This review provides an overview of the recent advances in microbiome research in relation to neuro(auto)immune and neurodegenerative conditions affecting humans, such as multiple sclerosis, neuromyelitis optica spectrum disorders, Parkinson disease, Alzheimer disease, Huntington disease, and amyotrophic lateral sclerosis. Study design and terminology used in this rapidly evolving, highly multidisciplinary field are summarized to empower and engage the neurology community in this “newly discovered organ.” FULL TEXT
Rodgaard et al., 2019
Rodgaard, E. M., Jensen, K., Vergnes, J. N., Soulieres, I., & Mottron, L.; “Temporal Changes in Effect Sizes of Studies Comparing Individuals With and Without Autism: A Meta-analysis;” JAMA Psychiatry, 2019; DOI: 10.1001/jamapsychiatry.2019.1956.
ABSTRACT:
IMPORTANCE:
The definition and nature of autism have been highly debated, as exemplified by several revisions of the DSM (DSM-III, DSM-IIIR, DSM-IV, and DSM-5) criteria. There has recently been a move from a categorical view toward a spectrum-based view. These changes have been accompanied by a steady increase in the prevalence of the condition. Changes in the definition of autism that may increase heterogeneity could affect the results of autism research; specifically, a broadening of the population with autism could result in decreasing effect sizes of group comparison studies.
OBJECTIVE:
To examine the correlation between publication year and effect size of autism-control group comparisons across several domains of published autism neurocognitive research.
DATA SOURCES:
This meta-analysis investigated 11 meta-analyses obtained through a systematic search of PubMed for meta-analyses published from January 1, 1966, through January 27, 2019, using the search string autism AND (meta-analysis OR meta-analytic). The last search was conducted on January 27, 2019.
STUDY SELECTION:
Meta-analyses were included if they tested the significance of group differences between individuals with autism and control individuals on a neurocognitive construct. Meta-analyses were only included if the tested group difference was significant and included data with a span of at least 15 years.
DATA EXTRACTION AND SYNTHESIS: Data were extracted and analyzed according to the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) reporting guideline using fixed-effects models.
MAIN OUTCOMES AND MEASURES:
Estimated slope of the correlation between publication year and effect size, controlling for differences in methods, sample size, and study quality.
RESULTS:
The 11 meta-analyses included data from a total of 27723 individuals. Demographic data such as sex and age were not available for the entire data set. Seven different psychological and neurologic constructs were analyzed based on data from these meta-analyses. Downward temporal trends for effect size were found for all constructs (slopes: -0.067 to -0.003), with the trend being significant in 5 of 7 cases: emotion recognition (slope: -0.028 [95% CI, -0.048 to -0.007]), theory of mind (-0.045 [95% CI, -0.066 to -0.024]), planning (-0.067 [95% CI, -0.125 to -0.009]), P3b amplitude (-0.048 [95% CI, -0.093 to -0.004]), and brain size (-0.047 [95% CI, -0.077 to -0.016]). In contrast, 3 analogous constructs in schizophrenia, a condition that is also heterogeneous but with no reported increase in prevalence, did not show a similar trend.
CONCLUSIONS AND RELEVANCE:
The findings suggest that differences between individuals with autism and those without the diagnosis have decreased over time and that possible changes in the definition of autism from a narrowly defined and homogenous population toward an inclusive and heterogeneous population may reduce our capacity to build mechanistic models of the condition. FULL TEXT
Patterson et al., 2018
Patterson, E. L., Pettinga, D. J., Ravet, K., Neve, P., & Gaines, T. A.; “Glyphosate Resistance and EPSPS Gene Duplication: Convergent Evolution in Multiple Plant Species;” Journal of Heredity, 2018, 109(2), 117-125; DOI: 10.1093/jhered/esx087.
ABSTRACT:
One of the increasingly widespread mechanisms of resistance to the herbicide glyphosate is copy number variation (CNV) of the 5-enolpyruvylshikimate-3-phosphate synthase (EPSPS) gene. EPSPS gene duplication has been reported in 8 weed species, ranging from 3 to 5 extra copies to more than 150 extra copies. In the case of Palmer amaranth (Amaranthus palmeri), a section of >300 kb containing EPSPS and many other genes has been replicated and inserted at new loci throughout the genome, resulting in significant increase in total genome size. The replicated sequence contains several classes of mobile genetic elements including helitrons, raising the intriguing possibility of extra-chromosomal replication of the EPSPS-containing sequence. In kochia (Kochia scoparia), from 3 to more than 10 extra EPSPS copies are arranged as a tandem gene duplication at one locus. In the remaining 6 weed species that exhibit EPSPS gene duplication, little is known about the underlying mechanisms of gene duplication or their entire sequence. There is mounting evidence that adaptive gene amplification is an important mode of evolution in the face of intense human-mediated selection pressure. The convergent evolution of CNVs for glyphosate resistance in weeds, through at least 2 different mechanisms, may be indicative of a more general importance for this mechanism of adaptation in plants. CNVs warrant further investigation across plant functional genomics for adaptation to biotic and abiotic stresses, particularly for adaptive evolution on rapid time scales. FULL TEXT
de Melo et al., 2019
de Melo, M. S., Nazari, E. M., Joaquim-Justo, C., Muller, Y. M. R., & Gismondi, E.; “Effects of low glyphosate-based herbicide concentrations on endocrine-related gene expression in the decapoda Macrobrachium potiuna;” Environmental Science and Pollution Research International, 2019, 26(21), 21535-21545; DOI: 10.1007/s11356-019-05496-1.
ABSTRACT:
Glyphosate-based herbicides (GBH) are the most used herbicides worldwide and are considered as endocrine-disrupting compounds (EDC) for non-target organisms. However, effects of GBH on their endocrine systems remain poorly understood. Thus, the aim of this study was to assess the effects of low concentrations of Roundup WG(R) on growth and reproduction process molecules in both males and females of the decapod crustacean Macrobrachium potiuna, by the relative transcript expression levels of the ecdysteroid receptor (EcR), the molt-inhibiting hormone (MIH), and the vitellogenin (Vg) genes. Prawns were exposed to three concentrations of GBH (0.0065, 0.065, and 0.28 mg L(-1)) for 7 and 14 days. The results revealed that only in males the three genes transcript levels were influenced by the GBH concentration, time of exposure, and the interaction between the concentrations and time of exposure, suggesting that males were more sensitive to GBH than females. For males, after 7 days of exposure at 0.065 mg L(-1), EcR and MIH were over-expressed, while the Vg expression was only over-expressed after 14 days. The present study highlighted that GBH impacted endocrine systems of M. potiuna. Moreover, EcR and MIH gene expressions could be promising EDC biomarkers of exposure in crustaceans. These results also indicate that GBH concentrations, considered secure by regulatory agencies, should be reviewed to minimize the effects on non-target organisms. FULL TEXT
Duforestel et al., 2019
Duforestel, Manon, Nadaradjane, Arulraj, Bougras-Cartron, Gwenola, Briand, Joséphine, Olivier, Christophe, Frenel, Jean-Sébastien, Vallette, François M., Lelièvre, Sophie A., & Cartron, Pierre-François; “Glyphosate Primes Mammary Cells for Tumorigenesis by Reprogramming the Epigenome in a TET3-Dependent Manner;” Frontiers in Genetics, 2019, 10; DOI: 10.3389/fgene.2019.00885.
ABSTRACT:
The acknowledgment that pollutants might influence the epigenome raises serious concerns regarding their long-term impact on the development of chronic diseases. The herbicide glyphosate has been scrutinized for an impact on cancer incidence, but reports demonstrate the difficulty of linking estimates of exposure and response analysis. An approach to better apprehend a potential risk impact for cancer is to follow a synergistic approach, as cancer rarely occurs in response to one risk factor. The known influence of glyphosate on estrogen-regulated pathway makes it a logical target of investigation in breast cancer research. We have used nonneoplastic MCF10A cells in a repeated glyphosate exposure pattern over 21 days. Glyphosate triggered a significant reduction in DNA methylation, as shown by the level of 5-methylcytosine DNA; however, in contrast to strong demethylating agent and cancer promoter UP peptide, glyphosate-treated cells did not lead to tumor development. Whereas UP acts through a DNMT1/PCNA/UHRF1 pathway, glyphosate triggered increased activity of ten-eleven translocation (TET)3. Combining glyphosate with enhanced expression of microRNA (miR) 182-5p associated with breast cancer induced tumor development in 50% of mice. Culture of primary cells from resected tumors revealed a luminal B (ER+/PR-/HER2-) phenotype in response to glyphosate-miR182-5p exposure with sensitivity to tamoxifen and invasive and migratory potentials. Tumor development could be prevented either by specifically inhibiting miR 182-5p or by treating glyphosate-miR 182-5p-cells with dimethyloxallyl glycine, an inhibitor of TET pathway. Looking for potential epigenetic marks of TET-mediated gene regulation under glyphosate exposure, we identified MTRNR2L2 and DUX4 genes, the hypomethylation of which was sustained even after stopping glyphosate exposure for 6 weeks. Our findings reveal that low pressure but sustained DNA hypomethylation occurring via the TET pathway primes cells for oncogenic response in the presence of another potential risk factor. These results warrant further investigation of glyphosate-mediated breast cancer risk. FULL TEXT
Chiu et al., 2018
Chiu, Y. H., Williams, P. L., Gillman, M. W., Gaskins, A. J., Minguez-Alarcon, L., Souter, I., Toth, T. L., Ford, J. B., Hauser, R., Chavarro, J. E., & Team, Earth Study; “Association Between Pesticide Residue Intake From Consumption of Fruits and Vegetables and Pregnancy Outcomes Among Women Undergoing Infertility Treatment With Assisted Reproductive Technology;” JAMA Internal Medicine, 2018, 178(1), 17-26; DOI: 10.1001/jamainternmed.2017.5038.
ABSTRACT:
IMPORTANCE:
Animal experiments suggest that ingestion of pesticide mixtures at environmentally relevant concentrations decreases the number of live-born offspring. Whether the same is true in humans is unknown. Objective: To examine the association of preconception intake of pesticide residues in fruits and vegetables (FVs) with outcomes of infertility treatment with assisted reproductive technologies (ART).
DESIGNT, SETTING, AND PARTICIPANTS:
This analysis included 325 women who completed a diet assessment and subsequently underwent 541 ART cycles in the Environment and Reproductive Health (EARTH) prospective cohort study (2007-2016) at a fertility center at a teaching hospital. We categorized FVs as having high or low pesticide residues using a validated method based on surveillance data from the US Department of Agriculture. Cluster-weighted generalized estimating equations were used to analyze associations of high- and low-pesticide residue FV intake with ART outcomes.
MAIN OUTCOMES AND MEASURES:
Adjusted probabilities of clinical pregnancy and live birth per treatment cycle.
RESULTS:
In the 325 participants (mean [SD] age, 35.1 [4.0] y; body mass index, 24.1 [4.3]), mean (SD) intakes of high- and low-pesticide residue FVs were 1.7 (1.0) and 2.8 (1.6) servings/d, respectively. Greater intake of high-pesticide residue FVs was associated with a lower probability of clinical pregnancy and live birth. Compared with women in the lowest quartile of high-pesticide FV intake (<1.0 servings/d), women in the highest quartile (>/=2.3 servings/d) had 18% (95% CI, 5%-30%) lower probability of clinical pregnancy and 26% (95% CI, 13%-37%) lower probability of live birth. Intake of low-pesticide residue FVs was not significantly related to ART outcomes.
CONCLUSIONS AND RELEVANCE:
Higher consumption of high-pesticide residue FVs was associated with lower probabilities of pregnancy and live birth following infertility treatment with ART. These data suggest that dietary pesticide exposure within the range of typical human exposure may be associated with adverse reproductive consequences. FULL TEXT
Pandey et al., 2019
Pandey, A., Dhabade, P., & Kumarasamy, A.; “Inflammatory Effects of Subacute Exposure of Roundup in Rat Liver and Adipose Tissue;” Dose Response, 2019, 17(2), 1559325819843380; DOI: 10.1177/1559325819843380.
ABSTRACT:
Roundup is a popular herbicide containing glyphosate as an active ingredient. The formulation of Roundup is speculated to have critical toxic effects, one among which is chronic inflammation. The present study analyzed adverse inflammatory effects in the liver and adipose tissue of rats after a subacute exposure of Roundup. Adult male rats were exposed to various doses of Roundup (0, 5, 10, 25, 50, 100 and 250 mg/kg bodyweight [bw] glyphosate) orally, everyday for 14 days. On day 15, liver and adipose tissues from dosed rats were analyzed for inflammation markers. C-reactive protein in liver, cytokines IL-1beta, TNF-alpha, IL-6, and inflammatory response marker, and prostaglandin-endoperoxide synthase were upregulated in liver and adipose of rats exposed to higher (100 and 250 mg/kg bw/d) doses of Roundup. Cumulatively, our data suggest development of inflammation in lipid and hepatic organs upon exposure to Roundup. Furthermore, liver histological studies showed formation of vacuoles, fibroid tissue, and glycogen depletion in the groups treated with doses of higher Roundup. These observations suggest progression of fatty liver disease in Roundup-treated adult rats. In summary, our data suggest progression of multiorgan inflammation, liver scarring, and dysfunction post short-term exposure of Roundup in adult male rats. FULL TEXT
Mills et al., 2019
Mills, P. J., Caussy, C., & Loomba, R.; “Glyphosate Excretion is Associated With Steatohepatitis and Advanced Liver Fibrosis in Patients With Fatty Liver Disease;” Clinical Gastroenterology and Hepatology, 2019; DOI: 10.1016/j.cgh.2019.03.045.
ABSTRACT:
Nonalcoholic fatty liver disease (NAFLD) is currently the most common chronic liver disease in developed countries.(1) Patients with nonalcoholic steatohepatitis (NASH) are considered to be at a higher risk of fibrosis progression and development to cirrhosis and hepatocellular carcinoma.
Among potential environmental contributors to the pathophysiology of NAFLD are exposure to pesticides and herbicides. Glyphosate, the primary weed-killing ingredient in Roundup (Monsanto, St Louis, MO), is sprayed on genetically modified crops and on many non–genetically modified grain crops and is found in these crops at harvest.
Rodents chronically fed with a low dosage of glyphosate exhibit signs of hepatotoxicity, liver congestion, necrosis, and DNA damage of the liver cells. This study examined excretion levels of glyphosate and its primary metabolite aminomethylphosphonic acid (AMPA) in a well-characterized and prospectively recruited cohort of patients with biopsy-proven NAFLD. FULL TEXT