Biology subjects

Antoniou, M. N.

Publications and source records attributed to Antoniou, M. N..

4 recordsLinked to original sources

bioRxiv2021

Glyphosate and its formulations Roundup Bioflow and RangerPro alter bacterial and fungal community composition in the rat caecum microbiome

The potential health consequences of glyphosate-induced gut microbiome alterations have become a matter of intense debate. As part of a multifaceted study investigating toxicity, carcinogenicity and multigenerational effects of glyphosate and its commercial herbicide formulations, we assessed changes in bacterial and fungal populations in the caecum microbiota of rats exposed prenatally until adulthood (13 weeks after weaning) to three doses of glyphosate (0.5, 5, 50 mg/kg body weight/day), or to the formulated herbicide products Roundup Bioflow and RangerPro at the same glyphosate-equivalent doses. Caecum bacterial microbiota were evaluated by 16S rRNA sequencing whilst the fungal population was determined by ITS2 amplicon sequencing. Results showed that both fungal and bacterial diversity were affected by the Roundup formulations in a dose-dependent manner, whilst glyphosate alone significantly altered only bacterial diversity. At taxa level, a reduction in Bacteroidota abundance, marked by alterations in the levels of Alloprevotella, Prevotella and Prevotellaceae UCG-003, was concomitant to increased levels of Firmicutes (e.g., Romboutsia, Dubosiella, Eubacterium brachy group or Christensenellaceae) and Actinobacteria (e.g., Enterorhabdus, Adlercreutzia, or Asaccharobacter). Treponema and Mycoplasma also had their levels reduced by the pesticide treatments. Analysis of fungal composition indicated that the abundance of the rat gut commensal Ascomycota Kazachstania was reduced while the abundance of Gibberella, Penicillium, Claviceps, Cornuvesica, Candida, Trichoderma and Sarocladium were increased by exposure to the Roundup formulations, but not to glyphosate. Altogether, our data suggest that glyphosate and its Roundup RangerPro and Bioflow caused profound changes in caecum microbiome composition by affecting the fitness of major commensals, which in turn reduced competition and allowed opportunistic fungi to grow in the gut, in particular in animals exposed to the herbicide formulations. This further indicates that changes in gut microbiome composition might influence the long-term toxicity, carcinogenicity and multigenerational effects of glyphosate-based herbicides.

pharmacology and toxicology↗

bioRxiv2021

In-depth comparative toxicogenomics of glyphosate and Roundup herbicides: histopathology, transcriptome and epigenome signatures, and DNA damage

Whether glyphosate-based herbicides (GBHs) are more potent than glyphosate alone at activating cellular mechanisms, which drive carcinogenesis remains controversial. As GBHs are more cytotoxic that glyphosate, we reasoned they may also be more capable of activating carcinogenic pathways. We tested this hypothesis by comparing the effects of glyphosate with Roundup GBHs both in vitro and in vivo. First, glyphosate was compared with representative GBHs namely MON 52276 (EU), MON 76473 (UK) and MON 76207 (USA) using the mammalian stem cell-based ToxTracker system. Here, MON 52276 and MON 76473, but not glyphosate and MON 76207, activated oxidative stress and unfolded protein responses. Second, molecular profiling of liver was performed in female Sprague-Dawley rats exposed to glyphosate or MON 52276 (both at 0.5, 50, 175 mg/kg bw/day glyphosate) for 90 days. MON 52276 but not glyphosate increased hepatic steatosis and necrosis. MON 52276 and glyphosate altered the expression of genes in liver reflecting TP53 activation by DNA damage and circadian rhythm regulation. Genes most affected in liver were similarly altered in kidneys. Small RNA profiling in liver showed decreased amounts of miR-22 and miR-17 from MON 52276 ingestion. Glyphosate decreased mir-30 while miR-10 levels were increased. DNA methylation profiling of liver revealed 5,727 and 4,496 differentially methylated CpG sites between the control and glyphosate and MON 52276 exposed animals respectively. Apurinic/apyrimidinic DNA damage formation in liver was increased with glyphosate exposure. Altogether, our results show that Roundup formulations cause more biological changes linked with carcinogenesis than glyphosate.

pharmacology and toxicology↗

bioRxiv2019

Relationship between faecal microbiota and plasma metabolome in rats fed NK603 and MON810 GM maize from the GMO90+ study

Safety concerns arising from the consumption of foods derived from genetically modified (GM) crops remains a highly debated and controversial subject. We report here a faecal microbiota compositional analysis in Wistar rats from the GMO90+ study, which fed glyphosate-tolerant NK603 (+/- Roundup application during cultivation) and Bt toxin MON810 GM maize for 6 months (at 11 and 33% composition of the feed) in comparison to their closest non-GM isogenic lines. We first integrated the faecal microbiota compositional data with results from plasma metabolomics to establish a baseline allowing us to understand which bacterial species can influence host metabolism. Coriobacteriaceae and Acetatifactor significantly predicted plasma metabolic profile in males, while Bifidobacterium and Ruminococcus were able to predict female plasma metabolites. We then investigated the differences in fecal microbiota composition between group of rats fed MON810 or NK603 GM maize varieties in comparison to their respective isogenic lines. Bacterial community richness was not altered by the test diets. There were no statistically significant differences in taxa abundance in the rat faecal microbiota that we could attribute to the consumption of either MON810 or NK603 GM maize varieties. In conclusion, we show that the consumption of the widely cultivated GM maize varieties NK603 and MON810 even up to 33% of the total diet had no effect on the status of the faecal microbiota compared to non-GM near isogenic lines.

molecular biology↗

bioRxiv2017

Transcriptome profiling reveals bisphenol A alternatives activate estrogen receptor alpha in human breast cancer cells

BackgroundPlasticizers with estrogenic activity, such as bisphenol A (BPA), have been reported to have potential adverse health effects in humans. Due to mounting evidence of these health effects and public pressure, BPA is being phased out by the plastics manufacturing industry and replaced by other bisphenol variants in \"BPA-free\" products.\n\nObjectivesWe have compared estrogenic activity of BPA to 6 bisphenol analogues (bisphenol S, BPS; bisphenol F, BPF; bisphenol AP, BPAP; bisphenol AF, BPAF; bisphenol Z, BPZ; bisphenol B, BPB) in three human breast cancer cell lines.\n\nMethodsEstrogenicity was assessed by cell growth in an estrogen receptor (ER)-mediated cell proliferation assay, and by the induction of estrogen response element (ERE)-mediated transcription in a luciferase assay. Gene expression profiles were determined in MCF-7 human breast cancer cells by microarray analysis and confirmed by Illumina-based RNA sequencing.\n\nResultsAll bisphenols showed estrogenic activity in promoting cell growth and inducing ERE-mediated transcription. BPAF was the most potent bisphenol, followed by BPB > BPZ ~ BPA > BPF ~ BPAP > BPS. The addition of ICI 182,780 antagonized the activation of ERs by bisphenols. Data mining of ToxCast high-throughput screening assays confirms our results but also shows divergence in the sensitivities of the assays. The comparison of transcriptome profile alterations resulting from BPA alternatives with an ER gene expression biomarker further indicates that all BPA alternatives act as ER agonists in MCF-7 cells. These results were confirmed by RNA sequencing.\n\nConclusionIn conclusion, BPA alternatives are not necessarily less estrogenic in a human breast cancer cell model. Three bisphenols (BPAF, BPB, and BPZ) were more estrogenic than BPA. The relevance of human exposure to BPA alternatives in hormone-dependent breast cancer risk should be investigated.

pharmacology and toxicology↗