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Microbiota dysbiosis associated with type 2 diabetes-like effects caused by chronic exposure to a mixture of chlorinated persistent organic pollutants in zebrafish [II]

ABSTRACT: Mixtures of chlorinated persistent organic pollutants (C-POPs-Mix) are chemically related risk factors for type 2 diabetes mellitus (T2DM); however, the effects of chronic exposure to C-POPs-Mix on microbial dysbiosis remain poorly understood. Herein, male and female zebrafish were exposed to C-POPs-Mix at a 1:1 ratio of five organochlorine pesticides and Aroclor 1254 at concentrations of 0.02, 0.1, and 0.5 μg/L for 12 weeks. We measured T2DM indicators in blood and profiled microbial abundance, richness, and evenness in the gut as well as transcriptomic and metabolomic alterations in the liver. Exposure to C-POPs-Mix significantly increased blood glucose levels while decreasing the abundance and alpha diversity of microbial communities only in females at concentrations of 0.02 and 0.1 μg/L. The majorly identified microbial contributors to microbial dysbiosis were Bosea minatitlanensis, Rhizobium tibeticum, Bifidobacterium catenulatum, B. adolescentis, and Collinsella aerofaciens. PICRUSt results suggested that altered pathways were associated with glucose and lipid production and inflammation, which are linked to changes in the transcriptome and metabolome of the zebrafish liver. Metagenomics outcomes revealed close relationships between intestinal and liver disruptions to T2DM-related molecular pathways. Thus, microbial dysbiosis in T2DM-triggered zebrafish occurred as a result of chronic exposure to C-POPs-Mix, indicating strong host–microbiome interactions.

ORGANISM(S): Danio rerio

PROVIDER: GSE233632 | GEO | 2023/06/01

REPOSITORIES: GEO

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Microbiota dysbiosis associated with type 2 diabetes-like effects caused by chronic exposure to a mixture of chlorinated persistent organic pollutants in zebrafish [I]

Project description:Mixtures of chlorinated persistent organic pollutants (C-POPs-Mix) are chemically related risk factors for type 2 diabetes mellitus (T2DM); however, the effects of chronic exposure to C-POPs-Mix on microbial dysbiosis remain poorly understood. Herein, male and female zebrafish were exposed to C-POPs-Mix at a 1:1 ratio of five organochlorine pesticides and Aroclor 1254 at concentrations of 0.02, 0.1, and 0.5 μg/L for 12 weeks. We measured T2DM indicators in blood and profiled microbial abundance, richness, and evenness in the gut as well as transcriptomic and metabolomic alterations in the liver. Exposure to C-POPs-Mix significantly increased blood glucose levels while decreasing the abundance and alpha diversity of microbial communities only in females at concentrations of 0.02 and 0.1 μg/L. The majorly identified microbial contributors to microbial dysbiosis were Bosea minatitlanensis, Rhizobium tibeticum, Bifidobacterium catenulatum, B. adolescentis, and Collinsella aerofaciens. PICRUSt results suggested that altered pathways were associated with glucose and lipid production and inflammation, which are linked to changes in the transcriptome and metabolome of the zebrafish liver. Metagenomics outcomes revealed close relationships between intestinal and liver disruptions to T2DM-related molecular pathways. Thus, microbial dysbiosis in T2DM-triggered zebrafish occurred as a result of chronic exposure to C-POPs-Mix, indicating strong host–microbiome interactions.

2023-06-01 | GSE233631 | GEO

Calcium signaling as a possible mechanism behind increased locomotor response in zebrafish larvae exposed to a human relevant persistent organic pollutant mixture or PFOS

Project description:Persistent organic pollutants (POPs) are widespread in the environment and bioaccumulate in organisms. Previously we observed hyperactivity of zebrafish larvae exposed to a mixture of POPs based on average blood levels from the Scandinavian population and identified perfluorooctanesulfonic acid (PFOS) as the driving agent for the behavioral changes. We exposed zebrafish larvae from 6 to 96 h post fertilization to the same mixture of POPs in two concentrations or a single PFOS exposure (0.3 and 2.06mg/L) and performed behavioral tests and transcriptomics analysis. Results confirmed previous observations that exposure to POPs and PFOS causes hyperactivity and higher anxiety levels. Transcriptomic analysis showed upregulation of transcripts related to muscle contraction. Muscle contraction is highly regulated by the availability of calcium in the sarcoplasmic reticulum. Ingenuity pathway analysis showed that one of the affected pathways in larvae exposed to the POPs mixture and PFOS was calcium signalling via the activation of the ryanodine receptors. We also found effect on lipid metabolism in those larvae exposed to the lower concentration of PFOS. By using omics technology, we observed that the altered behavioral pattern in exposed zebrafish larvae might be controlled directly by mechanisms affecting muscle function rather than from mechanisms connected to neurotoxicity.

2020-05-25 | GSE144525 | GEO

Effect of morphine treatment on microbiome in the context of microbial transplant.

Project description:Morphine causes microbial dysbiosis. In this study we focused on restoration of native microbiota in morphine treated mice and looked at the extent of restoration and immunological consequences of this restoration. Fecal transplant has been successfully used clinically, especially for treating C. difficile infection2528. With our expanding knowledge of the central role of microbiome in maintenance of host immune homeostasis17, fecal transplant is gaining importance as a therapy for indications resulting from microbial dysbiosis. There is a major difference between fecal transplant being used for the treatment of C. difficile infection and the conditions described in our studies. The former strategy is based on the argument that microbial dysbiosis caused by disproportionate overgrowth of a pathobiont can be out-competed by re-introducing the missing flora by way of a normal microbiome transplant. This strategy is independent of host factors and systemic effects on the microbial composition. Here, we show that microbial dysbiosis caused due to morphine can be reversed by transplantation of microbiota from the placebo-treated animals.

2016-06-01 | E-MTAB-3723 | biostudies-arrayexpress

Next Generation Sequencing (NGS) of zebrafish embryos transcriptome by pentachlorophenol (PCP) treatment

Project description:Purpose: We report the application of NGS for profiling the impacts of PCP exposure on the transcriptome of zebrafish embryos. Methods: mRNA profiles of 10 hpf/24 hpf PCP-treated and control zebrafish larvae were generated by deep sequencing using Illumina Hisq 2000 platform. The sequence reads that passed quality filters were analyzed at the transcript isoform level with TopHat followed by Cufflinks. Results: At 24 hpf, 6087 transcripts were affected after 200 μg/l exposure, in which 3593 were up-regulated and 2494 were down-regulated, and 1783 transcripts were affected after 5 μg/l exposure, in which 1031 were up-regulated and 752 were down-regulated. At 10 hpf, 2970 transcripts were affected after 200 μg/l exposure, in which 1526 were up-regulated and 1444 were down-regulated, and 1366 transcripts were affected after 5 μg/l exposure, in which 521 were up-regulated and 845 were down-regulated. Conclusions: This study provides a framework for the application of high-throughput RNA sequencing towards characterization of the impacts of PCP on whole zebrafish larval transcriptome.

2016-12-10 | GSE75921 | GEO

Next Generation Sequencing (NGS) of zebrafish larvae transcriptome by 2,2',4,4'-tetrabromodiphenyl ether (BDE47) treatment

Project description:Purpose: We report the application of NGS for profiling the impacts of BDE47 exposure on the transcriptome of zebrafish larvae. Methods: mRNA profiles of 6-day-old BDE47-treated and control zebrafish larvae were generated by deep sequencing using Illumina Hisq 2000 platform. The sequence reads that passed quality filters were analyzed at the transcript isoform level with TopHat followed by Cufflinks. Results: Compared BDE47 treatments with solvent control, 2235 transcripts were affected after 500 μg/l exposure, in which 1338 were up-regulated and 897 were down-regulated, and 552 transcripts were affected after 5 μg/l exposure, in which 155 were up-regulated and 397 were down-regulated. High concentration of BDE47 exposure resulted in more up-regulated genes. Conclusions: This study provides a framework for the application of high-throughput RNA sequencing towards characterization of the impacts of BDE47 on whole zebrafish larval transcriptome. Examination of zebrafish larvae transcriptomes with vehicle and 2 different concentrations of BDE47 treatments.

2014-12-16 | E-GEOD-59968 | biostudies-arrayexpress

Effects of Combined Persistant Organic Pollutants on Global Gene Expression in Human HepaRG Cells

Project description:The exposure to and contamination by Persistent Organic Pollutants (POPs), which include pesticides used worldwide and polyaromatic hydrocarbons, is detrimental to human health and diverse ecosystems. Although most mechanistic studies have focused on single compounds, living organisms are exposed to multiple environmental xenobiotics, simultaneously, throughout their lives. The experimental evidence useful for assessing the effects of exposure to pollutant mixtures is scarce. We investigated the effects of exposure to a combination of two POPs, which employ different xenosensors, on global gene expression in a human hepatocyte cell model, HepaRG. Whole genome microarrays were used to investigate the effects on the HepaRG transcriptome following exposure to the combination of POPs as compared to each compound individually.

2016-01-01 | GSE46874 | GEO

Danio rerio

Project description:Expression Analysis of Bisphenol A (0.1 uM), 17beta-estradiol (0.1 uM), and GSK4716 (0.1 uM) Exposure in Embryonic Zebrafish

| PRJNA169426 | ENA

Effects of Combined Persistant Organic Pollutants on Global Gene Expression in Human HepaRG Cells

2016-07-03 | E-GEOD-46874 | biostudies-arrayexpress

Colonic Gene expression of SPF mice fed either a Control Diet or a High Salt Diet

Project description:Compositional changes in the microbiota (dysbiosis) may be a basis for Irritable Bowel Syndrome (IBS) but biomarkers are currently unavailable to direct microbiota-directed therapy. We therefore examined whether changes in fecal β-defensin could be a marker of dysbiosis in a murine model. Experimental dysbiosis was induced using four interventions relevant to IBS: a mix of antimicrobials, westernized diets (high-fat/high-sugar and, high salt diets), or mild restraint stress. Fecal mouse β-defensin-3 and 16S rRNA-based microbiome profiles were assessed at baseline, during and following these interventions. Each intervention, except for mild restraint stress, altered compositional and diversity profiles of the microbiota. Exposure to antimicrobials or a high-fat/high-sugar diet, but not mild restraint stress, resulted in decreased fecal β-defensin-3 compared to baseline. In contrast, exposure to the high salt diet increased β-defensin-3 compared to baseline but this was not accompanied by discernible inflammatory changes in the host.

2023-07-11 | GSE225272 | GEO

An Immunological Synapse Formation Between T Regulatory Cells and Cancer-Associated Fibroblasts Promotes Tumour Development

Project description:The cells were lysed in a buffer consisting of 4% SDS, 0.1 M DTT, 100 mM Tris/HCl; pH 7.6 and heated for 5 minutes at 99℃. The protein extracts were processed according to theSp3 protocol. The reduced cysteine residues were alkylated in 200 mM iodoacetamide (Acros Organics). 20 μg of beads (1:1 mixture of hydrophilic and hydrophobic SeraMag carboxylate-modified beads; GE Life Sciences) were added to each sample in 50% ethanol. Protein clean-up was performed on a magnetic rack. The beads were washed twice with 80% ethanol followed by one wash with 100% acetonitrile (Fisher Chemical). The beads-captured proteins were digested overnight at 37 ℃ with 0.5 μg trypsin/LysC mix in 25 mM ammonium bicarbonate under vigorous shaking (1200 rpm, Eppendorf Thermomixer). The supernatants were collected and the peptides were purified by a modified Sp3 clean-up protocol and finally solubilized in the mobile phase A (0.1% formic acid in water), and sonicated. Peptide concentration was determined through absorbance measurement at 280 nm using a nanodrop instrument.

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