[en] Environmental pollutants have become an increasingly common health hazard in the last several decades. Recently, a number of studies have demonstrated the profound relationship between gut microbiota and our health. Gut microbiota are very sensitive to drugs, diet, and even environmental pollutants. In this review, we discuss the possible effects of environmental pollutants including antibiotics, heavy metals, persistent organic pollutants, pesticides, nanomaterials, and food additives on gut microbiota and their subsequent effects on health. We emphasize that gut microbiota are also essential for the toxicity evaluation of environmental pollution. In the future, more studies should focus on the relationship between environmental pollution, gut microbiota, and human health. - Highlights: • Gut microbiota are very important for our health. • Gut microbiota are very sensitive to drugs, diet, and even environmental pollutants. • Some environmental pollutants can induce gut microbiota dysbiosis and have multiple potential adverse effects on health. • Gut microbiota are essential for the evaluation of the toxicity of environmental pollutants. - This manuscript is the first to discuss and review the possible effects of environmental pollutants on gut microbiota and their subsequent effects on health.

[en] Highlights: • Microplastics could interact with microorganisms as well as gut microbiota. • Microplastics may affect host health through effects on gut microbiota. • Effects of microplastics on gut microbiota need more attention. -- Abstract: Microplastics (MPs) has gradually become a global environmental pollution problem and may harm human and animal health. In recent years, a large number of studies had shown that MPs had various toxicological effects on different organisms. At the same time, a number of studies had also shown that gut microbiota was closely related to host health and as a toxicity target for certain environmental pollutants including MPs. The fact is that more and more studies proved that MPs not only could interact with microorganism directly but also serve as a carrier for other pollutants and interacted with microorganism indirectly. In this review, we summarized the interactions between MPs and microorganisms as well as gut microbiota, and considered the possible impacts of MPs on environmental animal and human health, suggesting that the environmental microorganisms and the gut microbiota of animals were also the very important target for MPs. We hope that more studies pay more attention to focus on the relationship between MPs, gut microbiota, and environmental animals and human health in the future.

[en] Highlights: • SCCPs are ubiquitous in various environmental matrices and biota. • SCCPs pose lethality, carcinogenicity, metabolism-disrupting effect et al. • Toxicity mechanism of SCCPs related to oxidative stress, endocrine disruption et al. • More attention needs to be paid to novel toxic targets of SCCPs. -- Abstract: Short-chain chlorinated paraffin (SCCP) pollution has become a global threat. Much attention has been paid to their environmental occurrence and toxicity. In this review, we summarized the wide distribution of SCCPs in various environmental matrices and biota, including human beings. Toxicokinetics and the toxicities of SCCPs, including lethality, hepatotoxicity, developmental toxicity, carcinogenicity, endocrine- and metabolism-disrupting effects, and immunomodulatory effects have been considered. The mechanisms of SCCP toxicity are mainly related to oxidative stress, metabolic disturbance, endocrine disruption and binding to biomacromolecules. In the future, further studies of SCCPs should focus on searching for their novel toxicity targets, and uncovering their toxic effects using transcriptomics, proteomics, metabolomics, and mutigenerational toxicity.

[en] Highlights: • Nanoplastics posed great potential risks to aquatic organism and mammalian cell. • Nanoplastics induced significant alterations in MAPK pathway in zebrafish larvae. • The induction of oxidative stress and inflammation were correlated with p38 MAPK pathway. • Nanoplastics activated p38 MAPK pathway and finally induced apoptosis. Polystyrene nanoparticles (PS NPs), originated from breakdown of large plastic wastes, have already caused much concern for their environmental risks on health. This current study was aimed to reveal the toxicological mechanism of PS NPs on developing zebrafish and macrophage cells. To fulfill this purpose, 42 nm PS NPs were exposed to the early development stage of zebrafish for 5 days, the decreased heart rate and locomotor activity of zebrafish larvae were observed. The fluorescent PS NPs were used to precisely assess the accumulation of PS NPs in zebrafish larvae, and the results indicated that PS NPs not only accumulated in digestive system, but also infiltrated into the liver. More importantly, the transcriptomic analysis revealed that a total of 356 genes were differentially expressed and the KEGG class map showed significant differences in the MAPK pathway upon PS NPs treatment. Meanwhile, the induction of oxidative stress and inflammation were also observed in zebrafish larvae. Furthermore, PS NPs also induced oxidative damage and inflammatory response in RAW 264.7 cells, which activated p38 MAPK signal pathway and finally induced cell apoptosis. Our study provides a new understanding of MAPK signaling pathway involved in toxicity mechanism.

[en] Highlights: • Polystyrene microplastic decreased the secretion of mucin in gut of mice. • Polystyrene microplastic induced gut microbiota dysbiosis in mice. • Polystyrene microplastic induced hepatic lipid metabolism disorder in mice. Microplastic (MP) has become a concerning global environmental problem. It is toxic to aquatic organisms and can spread through the food chain to ultimately pose a threat to humans. In the environment, MP can interact with microbes and act as a microbial habitat. However, effects of polystyrene MP on the gut microbiota in mammals remain unclear. Here, male mice were exposed to two different sizes of polystyrene MP for 5 weeks to explore its effect. We observed that oral exposure to 1000 μg/L of 0.5 and 50 μm polystyrene MP decreased the body, liver and lipid weights in mice. Mucus secretion in the gut decreased in both sizes of polystyrene MP-treated groups. Regarding the gut microbiota, at the phylum level, polystyrene MP exposure decreased the relative abundances of Firmicutes and α-Proteobacteria in the feces. Furthermore, high throughput sequencing of the V3-V4 region of the 16S rRNA gene revealed significant changes in the richness and diversity of the gut microbiota in the cecums of polystyrene MP-treated mice. At the genus level, a total of 6 and 8 types of bacteria changed in the 0.5 and 50 μm polystyrene MP-treated groups, respectively. Furthermore, an operational taxonomic unit (OTU) analysis identified that 310 and 160 gut microbes were changed in the 0.5 and 50 μm polystyrene MP-treated groups, respectively. In addition, the hepatic triglyceride (TG) and total cholesterol (TCH) levels decreased in both 1000 μg/L 0.5 and 50 μm polystyrene MP-treated groups. Correspondingly, the relative mRNA levels of some key genes related to lipogenesis and TG synthesis decreased in the liver and epididymal fat. These results indicated that polystyrene MP could modify the gut microbiota composition and induce hepatic lipid disorder in mice; while the mouse is a common mammal model, consequently, the health risks of MP to animals should not be ignored.

[en] Highlights: • Propamocarb perturbed the transcription of hepatic genes related to lipid metabolism in mice. • Propamocarb induced gut microbiota dysbiosis in mice. • Propamocarb caused metabolic disorder in mice. Propamocarb (PM) is a widely used fungicide with property of affecting fatty acid and phospholipid biosynthesis in funguses. In this study, we explored its effects on mice gut microbiota and metabolism by exposing mice to 3, 30, and 300 mg/L PM through drinking water for a duration of 28 days. We observed that the transcription of hepatic genes related to regulate lipid metabolism were perturbed by PM exposure. The microbiota in the cecal contents and feces changed during or after PM exposure at phylum or genus levels. 16S rRNA gene sequencing for the cecal content revealed shifted in overall microbial structure after PM exposure, and operational taxonomic unit (OTU) analysis indicated that 32.2% of OTUs changed by 300 mg/mL PM exposure for 28 days. In addition, based on ¹H NMR analysis,a total of 20 fecal metabolites mainly including succinate, short chain fatty acids, bile acids and trimethylamine were found to be significantly influenced by exposure to 300 mg/L PM.,. These metabolites were tightly correlated to host metabolism. Our findings indicated that high doses of PM exposure could disturb mice metabolism through, or partly through, altering the gut microbiota and microbial metabolites.

[en] Highlights: • Microplastics can directly contact the intestines through different routes. • Microplastics may affect host health through effects on intestinal barrier. • Effects of microplastics on intestinal barrier need more attention. 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.

[en] Highlights: • Polystyrene microplastics increased in secretion of mucin in gut of zebrafish. • Polystyrene microplastics induced gut microbiota dysbiosis in adult zebrafish. • Polystyrene microplastics induced inflammation in the gut of zebrafish. Microplastic (MP) are environmental pollutants and have the potential to cause varying degrees of aquatic toxicity. In this study, the effects on gut microbiota of adult male zebrafish exposed for 14 days to 100 and 1000 μg/L of two sizes of polystyrene MP were evaluated. Both 0.5 and 50 μm-diameter spherical polystyrene MP increased the volume of mucus in the gut at a concentration of 1000 μg/L (about 1.456 × 10¹⁰ particles/L for 0.5 μm and 1.456 × 10⁴ particles/L for 50 μm). At the phylum level, the abundance of Bacteroidetes and Proteobacteria decreased significantly and the abundance of Firmicutes increased significantly in the gut after 14-day exposure to 1000 μg/L of both sizes of polystyrene MP. In addition, high throughput sequencing of the 16S rRNA gene V3-V4 region revealed a significant change in the richness and diversity of microbiota in the gut of polystyrene MP-exposed zebrafish. A more in depth analysis, at the genus level, revealed that a total of 29 gut microbes identified by operational taxonomic unit (OTU) analysis were significantly changed in both 0.5 and 50 μm-diameter polystyrene MP-treated groups. Moreover, it was observed that 0.5 μm polystyrene MP not only increased mRNA levels of IL1α, IL1β and IFN but also their protein levels in the gut, indicating that inflammation occurred after polystyrene MP exposure. Our findings suggest that polystyrene MP could induce microbiota dysbiosis and inflammation in the gut of adult zebrafish.

[en] Highlights: • Exposure of 1–4 μm PE-MPs caused microbiome dysbiosis in larval zebrafish. • PE-MPs decreased the mRNA expression level of glycolipid metabolism genes in larval zebrafish. • PE-MPs disrupted the metabolic profile of larval zebrafish. • The changed phospholipid metabolism was tightly related to microbiota change. 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.

[en] Highlights: • β-cypermethrin (β-CYP) causes mitochondrial dysfunction on murine macrophages. • β-CYP regulates the autophagy level in macrophages as time-dependent manner. • β-CYP causes the mitochondrial dysfunction and regulation of autophagy by upregulation of oxidative stress. • Autophagy plays a protective role in β-CYP-caused toxic effects via oxidative stress attenuation. -- Abstract: The immunotoxicity of synthetic pyrethroid (SPs) has garnered much attention, and our previous research demonstrated that β-CYP causes immunotoxicity and oxidative stress in macrophages. Nevertheless, the underlying mechanism remains largely unknown. In this study, the murine macrophage RAW 264.7 cells and murine peritoneal macrophages (PMs) were exposed to β-CYP. The results showed that β-CYP elevated intracellular ROS levels in both RAW 264.7 cells and PMs. Exposure to β-CYP also caused mitochondrial dysfunction with reduced mitochondrial membrane potential (MMP), intracellular ATP level and mitochondrial DNA (mtDNA) content in the two cell types. In addition, exposure of RAW 264.7 cells to β-CYP for 12 h and 24 h enhanced autophagy, with elevated Beclin1, Rab7, Lamp1 and LC3-II expression levels, while 48 h of exposure attenuated autophagy. In contrast, exposure of PMs to β-CYP for 12 h promoted autophagy, whereas exposure for 24 h and 48 h impaired autophagy. Cotreatment with an antioxidant, N-acetyl-L-cysteine (NAC), partially blocked the reduced MMP, intracellular ATP level and autophagy disturbance. Moreover, cotreatment with an autophagy agonist, rapamycin (RAPA), partially blocked mitochondrial dysfunction and oxidative stress in the two cell types, whereas cotreatment with an autophagy inhibitor, 3-methyladenine (3-MA), augmented the abovementioned toxic effects. Furthermore, mitochondrial ROS levels in both RAW 264.7 cells and PMs were elevated by exposure to β-CYP, and molecular docking showed that β-CYP docked with mouse respiratory chain complex I by binding to the ND2, ND4, and ND5 subunits of the protein complex. Taken together, the data obtained in the present study demonstrate that oxidative stress partially mediates mitochondrial dysfunction and autophagy disturbance upon exposure to β-CYP in macrophages, and autophagy plays a protective role against the toxic effects.