Nano- and micro-polystyrene plastics interfered the gut barrier function mediated by exosomal miRNAs in rats.

Microplastics (MPs) are widely distributed in the global environment, entering and accumulating in organisms in various ways and posing health threats. MPs can damage intestine; however, the mechanism by which MPs cause intestinal damage in rats is unclear. Here, rats were exposed to 50 nm PS-NPs or 5 µm PS-MPs for 4 weeks to evaluate the possible effects on intestinal barrier function and exosomal miRNAs expressions. The results showed that PS-NPs or PS-MPs disrupted the gut microbiota and affected gut barrier function at the biological level. In addition, PS-NPs and PS-MPs altered the composition of exosomal miRNAs in the intestinal and serum. Both PS-NPs and PS-MPs decreased the expression of miR-126a-3p in the intestinal and serum exosomes, which is an important signalling molecule involved in MPs induced gut barrier function disorder. More importantly, both in vitro and in vivo experiments indicated that miR-126a-3p was closely related to oxidative damage of intestinal cells through the PI3K-Akt pathway and eventually promote cell apoptosis by regulating the target gene of PIK3R2. Our study suggested that PS-NPs and PS-MPs could affect rat intestinal barrier function through an exosomal miRNA mediated pathway.

Extracellular vesicle miRNAs promote the intestinal microenvironment by interacting with microbes in colitis.

Inflammatory bowel disease (IBD) is a global disease with no cure. Disruption of the microbial ecosystem is considered to be an important cause of IBD. Extracellular vesicles (EVs) are vital participants in cell-cell and cell-organism communication. Both host-derived EVs and bacteria-derived membrane vesicles (OMVs) contribute to homeostasis in the intestine. However, the roles of EVs-miRNAs and MVs in host-microbe interactions in colitis remain unclear. In the present study, the animal model of colitis was established by dextran sulfate sodium (DSS) to investigate the changes of miRNAs in colonic EVs from colitis. Several miRNAs were significantly altered in colitis EVs. miR-181b-5p transplantation inhibited M1 macrophage polarization and promoted M2 polarization to reduce the levels of inflammation both in acute and remission of chronic colitis. miR-200b-3p could interact with bacteria and regulate the composition of the microbiota, which contributed to intestinal barrier integrity and homeostasis. Notably, MVs from normal feces could effectively reverse the composition of the intestinal microbiota, restore the intestinal barrier and rescue colitis, and BMVs from colitis would also have similar effects after miR-200b-3p treatment. Our results preliminarily identify a vesicle-based host-microbe interaction cycle in colitis and provide new ideas for colitis treatment.

Extracellular vesicles-mediated interaction within intestinal microenvironment in inflammatory bowel disease.

Background: The intestinal tract is a complicated ecosystem with dynamic homeostasis via interaction of intestine and microbiota. Inflammatory bowel disease (IBD) is chronic intestinal inflammation involving dysbiosis of intestinal microenvironment. Extracellular vesicles (EVs), as vital characteristics of cell-cell and cell-organism communication, contribute to homeostasis in intestine. Recently, EVs showed excellent potential for clinical applications in disease diagnoses and therapies. Aim of Review: Our current review discusses the modulatory functions of EVs derived from different sources in intestine, especially their effects and applications in IBD clinical therapy. EV-mediated interaction systems between host intestine and microbiota were established to describe possible mechanisms of IBD pathogenesis and its cure. Key Scientific Concepts of Review: EVs are excellent vehicles for delivering molecules containing genetic information to recipient cells. Multiple pieces of evidence have illustrated that EVs participate the interaction between host and microbiota in intestinal microenvironment. In inflammatory intestine with dysbiosis of microbiota, EVs as regulators target promoting immune response and microbial reconstruction. EVs-based immunotherapy could be a promising therapeutic approach for the treatment of IBD in the near future.

Embryonic toxicity of epoxiconazole exposure to the early life stage of zebrafish.

Epoxiconazole (EPX), as a broad-spectrum triazole fungicide, is widely used in agriculture to resist pests and diseases, while it may have potential toxicity to non-target organisms. In the present study, early developmental stage zebrafish were used as the subject organisms to assess the toxicity of EPX, and the possible mechanism of toxicity was also discussed by biochemical and transcriptomic analysis. Through embryo toxicity test, we had made it clear that the 96 h LC50 of embryo was 7.204 mg/L, and acute exposure to EPX effected hatching rate, heartbeats, body length and even morphological defects. Then, by being exposed to EPX for 7 days at concentrations of 175 (1/40 LC50), 350 (1/20 LC50) and 700 (1/10 LC50), biochemical parameters were affected, mainly manifested as increase of the triglyceride (TG) level and decrease of glucose content. Correspondingly, the transcription of genes related of glucose metabolism, lipid metabolism and cholesterol metabolism were also affected significantly in larval zebrafish. Moreover, some pathways, including lipid metabolism, glucose metabolism and amino acid metabolism were affected through transcriptome sequencing analysis in the larval zebrafish. Further data analysis based on the sequencing, EPX exposure also affected the expression of genes related to cell apoptosis. We further conformed that the bright fluorescence on the liver and bright spots near the liver by acridine orange staining. In addition, the mRNA levels of apoptosis related genes were also significantly affected in the EPX exposed larval zebrafish. Taken together, the work could provide an insight into toxic effects of EPX on the zebrafish larvae at embryo toxicity and transcriptional levels, providing some evidences for the toxic effects of triazole fungicides on non-target organisms.

Microplastic: A potential threat to human and animal health by interfering with the intestinal barrier function and changing the intestinal microenvironment.

Plastics are widely used in many fields due to their stable physical and chemical properties, and their global production and usage increase significantly every year, which leads to the accumulation of microplastics in the entire ecosystem. Numerous studies have shown that microplastics (MPs) have harmful effects on living organisms. This review aims to provide a comprehensive conclusion of the current knowledge of the impacts of MPs on the stability of the gut microenvironment, especially on the gut barrier. Studies showed that exposure to MPs could cause oxidative damage and inflammation in the gut, as well as the destruction of the gut epithelium, reduction of the mucus layer, microbial disorders, and immune cell toxicity. Although there are few reports directly related to humans, we hoped that this review could bring together more and more evidence that exposure to MPs results in disturbances of the intestinal microenvironment. Therefore, it is necessary to investigate their threats to human health further.

Combined hepatotoxicity of imidacloprid and microplastics in adult zebrafish: Endpoints at gene transcription.

Microplastics (MPs) and pesticides are two kinds of ubiquitous pollutants that can pose a health risk to aquatic organisms. However, researches about the combined effects of MPs and pesticides are very limited. A simple combined exposure model was established in this study, adult zebrafish were exposed to 100 µg/L imidacloprid (IMI), 20 µg/L polystyrene microplastics (PS), and a combination of PS and IMI (PS + IMI) for 21 days. The results demonstrated that exposure to PS and IMI inhibited the growth of zebrafish and altered the levels of glycolipid metabolism and oxidative stress-related biochemical parameters. While gene expression analysis revealed that, compared with PS or IMI treatment group, combined exposure caused a greater change in gene expression levels involving the process of glycolipid metabolism (Gk, Hk1, Aco, PPar-α, Cpt1, Acc, Fas, PPar-γ, Apo) and inflammatory response (IL-1ß, IL-6, IL-8, TNF-α, IL-10). The results demonstrated that even combined exposure of low concentrations of PS and IMI could cause more severe hepatotoxicity in zebrafish, especially in terms of gene transcription. And more combined toxicity studies are essential for MPs and pesticides risk assessment.

Effects of polyethylene microplastics on the microbiome and metabolism in larval zebrafish.

Various microplastics (MPs) are found in the environment and organisms. MP residues in organisms can affect health; however, their impacts on metabolism in aquatic organisms remain unclear. In this study, zebrafish embryos were exposed to polyethylene MPs with sizes ranging from 1 to 4 µm at concentrations of 0, 10, 100, and 1000 µg/L for 7 days. Through qPCR technology, the results indicated that zebrafish exposed to polyethylene MPs exhibited significant change in microbes of the phyla Firmicutes, Bacteroidetes, Proteobacteria, and Verrucomicrobia, etc. Moreover, 16S RNA gene sequencing revealed that there was a significant difference in alpha diversity between the control and 1000 µg/L MP-treated groups. At the genus level, the abundance of Aeromonas, Shewanella, Microbacterium, Nevskia and Methyloversatilis have increased remarkably. Conversely, the abundance of Pseudomonas, Ralstonia and Stenotrophomonas were significant reduction after MPs exposure. In addition, the levels of TG (triglyceride), TCHO (total cholesterol), NEFA (nonesterified fatty acid), TBA (total bile acid), GLU (glucose) and pyruvic acid significantly changed in MP-treated larval zebrafish, indicating that their metabolism was disturbed by MPs. Transcriptional levels of glucose and lipid metabolism-related genes showed a decreasing trend. Furthermore, LC/MS-based nontargeted metabolomics analysis demonstrated that a total of 59 phospholipid-related substances exhibited significant changes in larval fish treated with 1000 µg/L MPs. The mRNA levels of phospholipid metabolism-related genes were also obviously changed. Pearson correlation analysis indicated that the abundance of Aeromonas, Shewanella and Chitinibacter bacteria showed a negative correlation with most phospholipids, while Nevskia, Parvibacter and Lysobacter showed a positive correlation with most phospholipids. Based on these results, it is suggested that 1-4 µm PE-MPs could impact the microbiome and metabolism of larval zebrafish. All of these results indicated that the health risk of MPs cannot be ignored.