Additive Effect of Multi-strain Mixtures of Dead Bacterial Strains on Human Gut Microbiota in an In Vitro Model of Human Intestinal Microbiota
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PROVIDER: PRJEB71990 | ENA |
REPOSITORIES: ENA
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Project description:Humans are regularly exposed to mixtures of BPA alternative chemicals through their diets, consumer products and other sources. Like BPA, many alternatives perturb nuclear hormone receptors and are considered endocrine disrupting chemicals. We used high-throughput transcriptomics (HTTr) to evaluate the potency and potential modes of action of seven mixtures of BPA alternatives, along with their 12 individual components, in MCF-7 breast cancer cells. Our primary aim was to explore whether alternatives present in mixtures act additively. MCF-7 cells were exposed to chemicals (0.001 – 50 µM) for 48 h in serum-free conditions and TempO-Seq (BioSypder Inc.) was used to determine global and estrogen receptor alpha (ERα)-specific transcriptomic changes. Transcriptomic points of departure were derived using benchmark concentration (BMC) modelling. We first identified the concentration at which global transcriptional activity was robustly altered. Then, a novel ERα transcriptomic biomarker was used to identify ERα agonists and model a predicted ERα activation point of departure. Mixtures modelling was employed to predict potency of BPA alternatives and test for additive effects in vitro. Ingenuity Pathway Analysis (IPA; Qiagen) was used to identify upstream regulators and canonical pathways from genes fitting BMCs. All seven mixtures had additive effects across all transcriptomic points of departure modelled. BPAF was the most potent individual chemical tested overall, followed by BPA and BPC. The ERα transcriptomic biomarker classified all mixtures as ERα activators along with several individual BPA alternatives. Pathway analysis revealed that all mixtures and most individual components perturbed similar upstream regulators and pathways, suggesting common modes of action. These data support the use of HTTr as part of new approach methodologies to assess the toxicological potency of mixtures in vitro.
2025-06-30 | GSE276869 | GEO
Project description:High-throughput transcriptomics screening of mixtures of BPA alternatives reveal additive effects in vitro
| PRJNA1159318 | ENA
Project description:Adult female three-spined stickleback fish (Gasterosteus aculeatus) were exposed to 10 individual chemicals, 26 mixtures of these chemicals, or control conditions in a flow-through system for 4 days. Transcriptomics was performed on liver samples by microarray. The main aims were to determine molecular signatures induced by these chemicals in the three-spined stickleback, discover whether these persisted in chemical mixtures and identify non-additive molecular responses in chemical mixtures exposures.
2018-03-01 | E-MTAB-5581 | biostudies-arrayexpress
Project description:The diets of industrialized countries reflect the increasing use of processed foods, often with the inclusion of novel food additives. Xanthan gum is a complex polysaccharide with unique rheological properties that have established its use as a widespread stabilizer and thickening agent. Xanthan gum’s chemical structure is distinct from the host and dietary polysaccharides that are more commonly expected to transit the gastrointestinal tract, and little is known about its direct interaction with the gut microbiota, which plays a central role in digestion of other dietary fiber polysaccharides. Here, we show that the ability to digest xanthan gum is surprisingly common in industrialized human gut microbiomes and appears contingent on a single uncultured bacterium in the family Ruminococcaceae. Our data reveal that this primary degrader cleaves the xanthan gum backbone before processing the released oligosaccharides using additional enzymes. Surprisingly, some individuals harbor a Bacteroides intestinalis that is incapable of consuming polymeric xanthan gum but grows on oligosaccharide products generated by the Ruminococcaceae. Feeding xanthan gum to germfree mice colonized with a human microbiota containing the uncultured Ruminococcaceae supports the idea that this additive can drive expansion of this primary degrader along with exogenously introduced Bacteroides intestinalis. Our work demonstrates the existence of a potential xanthan gum food chain involving at least two members of different phyla of gut bacteria and provides an initial framework to understand how widespread consumption of a recently introduced food additive influences human microbiomes.
2022-02-28 | PXD031522 | Pride
Project description:The recent development of a custom cDNA microarray platform for one of thé standard organisms in aquatic toxicology, Daphnia magna, opened up new ways to mechanistic insights of toxicological responses. In this study, gene expression and (sub)organismal responses (Cellular Energy Allocation, growth) were assayed after short-term waterborne metal exposure. Microarray analysis of Ni-exposed daphnids revealed several affected functional gene classes, of which the largest ones were involved in different metabolic processes (mainly protein and chitin related processes), cuticula turnover, transport and signal transduction. Furthermore, genes involved in oxygen transport and heme metabolism (hemoglobin, δ-aminolevilunate synthase) were down-regulated. Applying a Partial Least Squares regression on nickel fingerprints and biochemical (sub)organismal parameters revealed a set of co-varying genes (hemoglobin, RNA terminal phosphate cyclase, a ribosomal protein and an “unknown” gene fragment). An inverse relationship was seen between the mRNA expression levels of different cuticula proteins and available energy reserves. In addition to the nickel exposure, daphnids were exposed to binary mixtures of nickel and cadmium or nickel and lead. Using multivariate analysis techniques, the mixture gene expression fingerprints (Ni2++Cd2+, Ni2++Pb2+) were compared to those of the single metal treatments (Ni2+, Cd2+, Pb2+). It was hypothesized that the molecular fingerprints of the mixtures would be additive combinations of the gene expression profiles of the individual compounds present in the mixture. However, our results clearly showed additionally affected pathways after mixture treatment (e.g. additional affected genes involved in carbohydrate catabolic processes and proteolysis), indicating interactive molecular responses which are not merely the additive sum of the individual metals. These findings, although indicative of the complex nature of mixture toxicity evaluation, underline the potential of a toxicogenomics approach in gaining more mechanistic information on the effects of single compounds and mixtures.
2009-02-27 | GSE13866 | GEO
Project description:Sparus aurata gut microbiota (control and additive diet) Metagenome
| PRJNA701881 | ENA
Project description:Expression profiling analyses for 5 maize inbreds and 4 hybrids, chosen to represent diversity in genotypes and heterosis responses, revealed a correlation between genetic diversity and transcriptional variation. The majority of differentially expressed genes in each of the different hybrids exhibited additive expression patterns, and ~25% exhibited statistically significant non-additive expression profiles. Among the non-additive profiles, ~80% exhibited hybrid expression levels between the parental levels, ~20% exhibited hybrid expression levels at the parental levels and ~1% exhibited hybrid levels outside the parental range. These findings indicate that the frequencies of additive and non-additive expression patterns are very similar across a range of hybrid lines. Keywords: Genotype comparison series
2008-01-26 | GSE10236 | GEO
Project description:Synthetic mixtures of Campylobacter jejuni strains
| PRJEB55470 | ENA
Project description:Mine-tailing soil mixtures Raw sequence reads
| PRJNA484825 | ENA
Project description:Background: Organophosphate esters (OPEs), used as flame retardants and plasticizers, are present ubiquitously in the environment. Previous studies suggested that exposure to OPEs may be detrimental to female fertility in humans. However, no experimental information is available on the effects of OPE mixtures on ovarian granulosa cells, which play essential roles in female reproduction. Objectives: The goal of this study was to elucidate the effects of OPE mixtures representative of those found in Canadian house dust on ovarian granulosa cells. Methods: We used high-content imaging to investigate the effects an environmentally relevant OPE mixtures on KGN human granulosa cell phenotypes. Perturbation to steroidogenesis was assessed using ELISA and qRT-PCR. A high-throughput transcriptomic approach, TempO-Seq, was used to identify transcriptional changes in a targeted panel of genes. Effects on lipid homeostasis were explored using cholesterol assay and global lipidomic profiling. Results: OPE mixtures with distinct structural characteristics altered multiple phenotypic features of KGN cells with different potencies. The mixtures increased basal production of steroid hormones; this was mediated by significant changes in the expression of critical transcripts involved in steroidogenesis. Further, the total-OPE mixture disrupted cholesterol homeostasis and the composition of intracellular lipid droplets. Discussion: Exposure to house dust-derived mixtures of OPEs may adversely affect female reproductive health by altering a multitude of phenotypic and functional endpoints in granulosa cells. This study provides novel insights into the mechanisms of actions underlying the toxicity induced by OPE mixtures and highlights the need to examine the effects of human relevant chemical mixtures.
2024-07-03 | GSE247310 | GEO