Co-exposure with cadmium elevates the toxicity of microplastics: Trojan horse effect from the perspective of intestinal barrier.

Microplastics (MPs) have been shown to adsorb heavy metals and serve as vehicles for their environmental transport. To date, insufficient studies have focused on enterohepatic injury in mice co-exposed to both MPs and cadmium (Cd). Here, we report that Cd adsorption increased the surface roughness and decreased the monodispersity of PS-MPs. Furthermore, exposure to both PS-MPs and Cd resulted in a more severe toxic effect compared to single exposure, with decreased body weight gain, shortened colon length, and increased colonic and hepatic inflammatory response observed. This can be attributed to an elevated accumulation of Cd resulting from increased gut permeability, coupled with the superimposed effects of oxidative stress. In addition, using 16 S sequencing and fecal microbiota transplantation, it was demonstrated that gut microbiota dysbiosis plays an essential role in the synergistic toxicity induced by PS-MPs and Cd in mice. This study showed that combined exposure to MPs and Cd induced more severe intestinal and liver damage in mice compared to individual exposure, and provided a new perspective for a more systematic risk assessment process related to MPs exposure.

Polystyrene nanoplastics exacerbated Pb-induced liver toxicity in mice.

Nanoplastics are widely distributed in the environment and can adsorb heavy metals, which poses a potential threat to human health through food chain. It is necessary to assess the combined toxicity of nanoplastics and heavy metals. The adverse effect of Pb and nanoplastics on liver, single or in combination, was evaluated in this study. The results showed that the Pb content in co-exposure group of nanoplastics and Pb (PN group) was higher than the group exposed to Pb alone (Pb group). And more severe inflammatory infiltration was observed in liver sections of PN group. The level of inflammatory cytokines and malondialdehyde were increased, while the superoxide dismutase activity was decreased in liver tissues of PN group. Moreover, the gene expression level of nuclear factor-erythroid 2-related factor 2, nicotinamide adenine dinucleotide phosphate:quinine oxidoreductase 1 and catalase, which is related to antioxidation, was downregulated. And the expression level of cleaved-Caspase9 and cleaved-Caspase3 were increased. However, with the supplementation of oxidative stress inhibitor N-Acetyl-L-cysteine, liver damage shown in PN group was evidently alleviated. In summary, nanoplastics evidently exacerbated the deposition of Pb in liver and potentially aggravated the Pb-induced liver toxicity by activating oxidative stress.

TiO2 nanoparticles combined with polystyrene nanoplastics aggravated reproductive toxicity in female mice via exacerbating intestinal barrier disruption.

BACKGROUND: TiO2 nanoparticles (NPs), a widely used food additive in the food industry, have been shown to aggravate the progress of metabolic diseases. Nanoplastics (NPLs) are an emerging contaminant widely present in the food system and have been shown to induce ovarian disorders in mammals. Noteworthy, they can be ingested by humans through 'contaminated' food, whereas the potential toxicity of NPLs and TiO2 NPs combined remains unclear. In the present study, we investigated the potential effects and mechanisms of co-exposure to polystyrene (PS) NPLs and TiO2 NPs on the ovary in female mice. RESULTS: Our results revealed that the co-exposure of TiO2 NPs and PS NPLs caused significant injury to ovarian structure and function, but individual exposure had no effect. Moreover, compared to the TiO2 NPs group, co-exposure aggravated the intestinal barrier damage in mice, increasing the bioaccumulation of TiO2 NPs in the ovary. After being supplemented with the oxidative stress inhibitor N-acetyl-l-cysteine, the expression of ovarian antioxidant genes increased, and the ovarian structural and functional injury in co-exposure mice reverted to normal levels. CONCLUSION: The present study demonstrated that co-exposure to PS NPLs and TiO2 NPs can cause more severe female reproductive dysfunction and deepens the toxicological insights between NPLs and NPs. © 2023 Society of Chemical Industry.

Lactiplantibacillus plantarum P101 alleviated lead-induced more severe hepatic injury in obese mice, by promoting fecal lead excretion and enhancing antioxidative defense system.

AIMS: Lead (Pb) is a toxic heavy metal that has been intensively studied, but its toxicity in sub-healthy people remains unclear. This study aims to investigate the adverse effects of Pb in the obese population and validate the feasibility of a potential probiotic strain for the treatment of Pb poisoning and diet-induced obesity. METHODS AND RESULTS: Male Kunming mice were fed a high-fat/high-sugar (HFHS) diet for 6 weeks, then received Pb exposure and Lactiplantibacillus plantarum P101 supplementation for 2 weeks. The histopathology of the liver and colon was observed, and biochemical indicators and gene expression levels were measured. CONCLUSIONS: Here, we reported that Pb exposure exacerbated the existing oxidative stress and gut barrier injury in obese mice, leading to more severe Pb accumulation, and hepatic inflammatory injury compared with normal diet-fed mice. It is worth noting that the P101 treatment significantly reduced Pb accumulation by promoting fecal Pb excretion and enhanced the antioxidant capacity of mice. After P101 treatment, obesity-related indicators were downregulated, and the hepatic injury and gut barrier disruption in mice were alleviated effectively.

Lead exposure exacerbates adverse effects of HFD on metabolic function via disruption of gut microbiome, leading to compromised barrier function and inflammation.

PURPOSE: The toxicity of lead (Pb) has been intensively studied, while the adverse effects in the population on a high-fat diet (HFD) remain unclear. This study compared the different biologic effects of Pb in CHOW and HFD-fed mice and investigated the important role that gut microbiota may play. METHODS: C57BL/6 mice were fed a CHOW diet and HFD with or without 1 g/L Pb exposure through drinking water for 8 weeks. Using oral glucose tolerance test, histopathological observation, real-time fluorescence quantitative PCR, enzyme-linked immunosorbent assay, and 16S high-throughput sequencing to compare the Pb toxicity, fecal microbiota transplantation was conducted to investigate the key role of gut microbiota. RESULTS: The metabolic disorders induced by HFD were aggravated by chronic Pb intake, and HFD exacerbated the Pb accumulation in the colon by 96%, 32% in blood, 27% in the liver, and 142% in tibiae. Concomitantly, Pb induced more serious colonic injury, further disturbing the composition of gut microbiota in the HFD-fed mice. Moreover, altered fecal microbiota by HFD and Pb directly mediated metabolic disorders and colonic damage in recipient mice, which emphasized the importance of gut microbiota. CONCLUSION: These findings indicated that the population with HFD has lower resistance and would face more security risks under Pb pollution, and pointed out the importance of assessing the health impacts of food contaminants in people with different dietary patterns.

High-fat diet in mice led to increased severity of spermatogenesis impairment by lead exposure: perspective from gut microbiota and the efficacy of probiotics.

BACKGROUND: The mechanism of multifactorial spermatogenesis impairment is unclear. This study aimed to investigate the reproductive toxicity of lead (Pb) in mice fed a high-fat diet (HFD) and to delineate the important role of gut microbiota. RESULTS: Results showed that, compared with mice fed a normal diet (ND), Pb exposure caused more severe spermatogenesis impairment in HFD-fed mice, including decreased sperm count and motility, seminiferous tubule injury, serum and intratesticular testosterone decline, and downregulated expression level of spermatogenesis-related genes. Besides, 16S sequencing indicated that HFD-fed mice had increased severity of gut microbiota dysbiosis by Pb exposure compared to ND-fed mice. With fecal microbiota transplantation, the same trend of spermatogenesis impairment occurred in recipient mice, which confirmed the important role of gut microbiota. Moreover, probiotics supplementation restored the gut microbial ecosystem, and thus improved spermatogenic function. CONCLUSION: Our work suggested that a population with HFD might face more reproductive health risks upon Pb exposure, and revealed an intimate linkage between microbiota dysbiosis and spermatogenesis impairment, accompanied by the potential usefulness of probiotics as prophylactic and therapeutic. © 2022 Society of Chemical Industry.

Trojan horse in the intestine: A review on the biotoxicity of microplastics combined environmental contaminants.

With the reported ability of microplastics (MPs) to act as "Trojan horses" carrying other environmental contaminants, the focus of researches has shifted from their ubiquitous occurrence to interactive toxicity. In this review, we provided the latest knowledge on the processes and mechanisms of interaction between MPs and co-contaminants (heavy metals, persistent organic pollutants, pathogens, nanomaterials and other contaminants) and discussed the influencing factors (environmental conditions and characteristics of polymer and contaminants) that affect the adsorption/desorption process. In addition, the bio-toxicological outcomes of mixtures are elaborated based on the damaging effects on the intestinal barrier. Our review showed that the interaction processes and toxicological outcomes of mixture are complex and variable, and the intestinal barrier should receive more attention as the first line of defensing against MPs and environmental contaminants invasion. Moreover, we pointed out several knowledge gaps in this new research area and suggested directions for future studies in order to understand the multiple factors involved, such as epidemiological assessment, nanoplastics, mechanisms for toxic alteration and the fate of mixtures after desorption.

Combination of Houttuynia cordata polysaccharide and Lactiplantibacillus plantarum P101 alleviates acute liver injury by regulating gut microbiota in mice.

BACKGROUND: Polysaccharides and probiotics can play an outstanding role in the treatment of liver disease by regulating gut microbiota. Recently, the combined therapeutic effect of probiotics and polysaccharides has attracted the attention of researchers. Houttuynia cordata polysaccharide (HCP) combined with Lactiplantibacillus plantarum P101 was used to prevent carbon tetrachloride (CCl4 )-induced acute liver injury (ALI) in mice, and its effect on gut microbiota regulation was explored. RESULTS: Results showed that, in mice, HCP combined with L. plantarum P101 significantly alleviated oxidative stress and inflammatory injury in the liver by activating Nrf2 signals and inhibiting NF-κB signals. The analysis of gut microbiota revealed that the combination of HCP and L. plantarum P101 increased the abundance of beneficial bacteria such as Alloprevotella, Roseburia, and Akkermansia, but reduced that of the pro-inflammatory bacteria Alistipes, Enterorhabdus, Anaerotruncus, and Escherichia-Shigella. Correlation analysis also indicated that the expression of Nrf2 and TLR4/NF-κB was connected to the changes in gut microbiota composition. Houttuynia cordata polysaccharide combined with L. plantarum P101 can regulate the gut microbiota and then mediate the gut-liver axis to activate the antioxidant pathway and inhibit inflammatory responses, thereby alleviating CCl4 -induced ALI. CONCLUSION: Our study provided a new perspective on the use of polysaccharides combined with probiotics in the treatment of liver disease. © 2022 Society of Chemical Industry.