As a common fungicide, tebuconazole are ubiquitous in the natural environment and poses many potential risks. In this study, we examined the effects of exposure to tebuconazole on colitis in mice and explored its underlying mechanism. Specifically, exposure to tebuconazole could cause structural damage and inflammatory cell infiltration in colon tissue, activate the expression of inflammation-related genes, disrupt the expression of barrier function-related genes, and induce the colonic inflammation in mice. Similarly, exposure to tebuconazole could also exacerbate DSS-induced colitis in mice. In addition, we found that tebuconazole also could change the composition of the gut microbiota. In particular, tebuconazole significantly increases the relative abundance of Akkermansia of mice. Moreover, tebuconazole resulted in metabolic profiles disorders of the serum, leading to significant changes in the relative contents of metabolites involving glycolipid metabolism and amino acid metabolism. Particularly, the results of the gut microbiota transplantation experiment showed that exposure to tebuconazole could induced colonic inflammation in mice in a gut microbiota–dependent manner. Taken together, these results indicated that tebuconazole could induce colitis in mice via regulating gut microbiota. Our findings strongly support the concept that the gut microbiota is a key trigger of inflammatory bowel disease caused by pesticide intake.

Antibiotics are omnipresent in the environment due to their widespread use, and they have wide-ranging negative impacts on organisms. Virus resistance differs substantially between domesticated Apis mellifera and wild Apis cerana, although both are commonly raised in China. Here, we investigated whether antibiotics can increase the sensitivity of honey bees to viral infection using the Israeli acute paralysis virus (IAPV) and tetracycline as representative virus and antibiotic. Although IAPV multiplied to lower levels in A. cerana than A. mellifera, resulting in decreased mortality (P < 0.01), there was no significant difference in immune responses to viral infection between the two species. Adult worker bees (A. cerana and A. mellifera) were treated with or without tetracycline to demonstrate the prominent role of gut microbiota against viral infection, and found Lactobacillus played a vital antiviral role in A. cerana. In A. cerana but not A. mellifera, tetracycline treatment reduced clearly bee survival and increased susceptibility to IAPV infection (P < 0.01). Our findings revealed that long-term antibiotic treatment in A. mellifera had altered the native gut microbiome and promoted the sensitivity to viral infection. We highlight the effects of antibiotics exposure on resistance to microbial and viral infection.

Perfluorooctanesulfonic acid (PFOS) is a persistent anthropogenic chemical that can affect the thyroid hormone system in humans and animals. In adults, thyroid hormones (THs) are regulated by the hypothalamic-pituitary-thyroid (HPT) axis, but also by organs such as the liver and potentially the gut microbiota. PFOS and other xenobiotics can therefore disrupt the TH system at various locations and through different mechanisms. To start addressing this, we exposed adult male rats to 3 mg PFOS/kg/day for 7 days and analysed effects on multiple organs and pathways simultaneously by transcriptomics. This included four primary organs involved in TH regulation, namely hypothalamus, pituitary, thyroid, and liver. To investigate a potential role of the gut microbiota in thyroid hormone regulation, two additional groups of animals were dosed with the antibiotic vancomycin (8 mg/kg/day), either with or without PFOS. PFOS exposure decreased thyroxine (T4) and triiodothyronine (T3) without affecting thyroid stimulating hormone (TSH), resembling a state of hypothyroxinemia. PFOS exposure resulted in 50 differentially expressed genes (DEGs) in the hypothalamus, 68 DEGs in the pituitary, 71 DEGs in the thyroid, and 181 DEGs in the liver. A concomitant compromised gut microbiota did not significantly change effects of PFOS exposure. Organ-specific DEGs did not align with TH regulating genes; however, genes associated with vesicle transport and neuronal signaling were affected in the hypothalamus, and phase I and phase II metabolism in the liver. This suggests that a decrease in systemic TH levels may activate the expression of factors altering trafficking, metabolism and excretion of TH. At the transcriptional level, little evidence suggests that the pituitary or thyroid gland is involved in PFOS-induced TH system disruption.

The intestinal microbiota has a key role in human health via the interaction with the somatic and immune cells in the digestive tract environment. Food, through matrix effect, nutrient and non-nutrient molecules, is a key regulator of microbiota diversity. As a food contaminant, the pesticide chlorpyrifos (CPF) has an effect on the composition of the intestinal microbiota and induces perturbation of microbiota. Prebiotics (and notably inulin) are known for their ability to promote an equilibrium of the microbiota that favours saccharolytic bacteria. The SHIME® dynamic in vitro model of the human intestine was exposed to CPF and inulin concomitantly for 30 days, in order to assess variations in both the bacterial populations and their metabolites. Various analyses of the microbiota (notably temporal temperature gradient gel electrophoresis) revealed a protective effect of the prebiotic through inhibition of the enterobacterial (E. coli) population. Bifidobacteria were only temporarily inhibited at D15 and recovered at D30. Although other potentially beneficial populations (lactobacilli) were not greatly modified, their activity and that of the saccharolytic bacteria in general were highlighted by an increase in levels of short-chain fatty acids and more specifically butyrate. Given the known role of host-microbiota communication, CPF's impact on the body's homeostasis remains to be determined.

Paraquat, a widely used herbicide, causes environmental pollution, and liver injury in humans and animals. As a natural compound in fruits, ellagic acid (EA) shows anti-inflammatory and antioxidant effects. This study examines the beneficial effects of dietary EA against the paraquat-induced hepatic injury and further explores the underlying molecular mechanisms using a piglet model. Post-weaning piglets are fed basal diet supplemented with 50 mg/kg, 100 mg/kg, or 200 mg/kg EA for 3 weeks. At week 2, hepatic injury is induced by 4 mg/kg paraquat followed by 7 days recovery. EA supplementation significantly mitigates paraquat-induced hepatic fibrosis, steatosis, and high apoptotic rate. In agreement, EA supplementation reduces serum pro-inflammatory levels, ameliorates inflammatory cells infiltration into hepatic tissue, which are associated with suppressed NF-κB signaling during paraquat exposure. In addition, EA supplementation significantly improves activities of antioxidative enzymes which were correlated with activated Nrf2/Keap 1 signaling during paraquat exposure. Furthermore, EA supplementation restores cecal microbial community during paraquat exposure. The protective effect of EA is strongly linked with increased relative abundance of Lactobacillus reuteri and Lactobacillus amylovorus. Taken together, EA supplementation effectively reduced the occurrence of hepatic oxidative damage and inflammation induced by paraquat through modulating cecal microbial communities, which provides a novel nutritional therapeutic strategy for hepatic injury.

In recent years, pollution of antibiotics and heavy metal has often been reported in organic wastes. Saprophytic insects have been recorded as biological control agents in organic waste management. During organic waste conversion, the intestinal bacteria of the saprophytic insects play an important role in digestion, physiology, immunity and prevention of pathogen colonization. Black soldier fly (BSF) Hermetia illucens has been widely used as saprophytic insects and showed tolerance to sulfonamides (SAs) and cadmium (Cd). Diversity and changes in gut microbiota of black soldier fly larvae (BSFL) were evaluated through 16S rRNA high-throughput sequencing, and a decrease in diversity of gut microbiota along with an increase in SAs stress was recorded. Major members identified were Actinomycetaceae, Enterobacteriaceae, and Enterococcaceae. And fourteen multi-resistance Klebsiella pneumoniae strains were isolated. Two strains BSFL7-B-5 (from middle midgut of 7-day BSFL) and BSFL11-C-1 (from posterior midgut of 11-day BSFL) were found to be low-toxic and multi-resistance. The adsorption rate of SAs in 5 mg/kg solutions by these two strains reached 65.2% and 61.6%, respectively. Adsorption rate of Cd in 20 mg/L solutions was 77.2% for BSFL7-B-5. The strain BSFL11-C-1 showed higher than 70% adsorption rates of Cd in 20, 30 and 40 mg/L solutions. This study revealed that the presence of multi-resistance bacterial strains in the gut of BSFL helped the larvae against SAs or Cd stress. After determining how and where they are used, selected BSFL gut bacterial strains might be utilized in managing SAs or Cd contamination at suitable concentrations in the future.

Lead is a metal that exists naturally in the Earth's crust and is a ubiquitous environmental contaminant. The alleviation of lead toxicity is important to keep human health under lead exposure. Biosynthesized selenium nanoparticle (SeNPs) and selenium-enriched Lactobacillus rhamnosus SHA113 (Se-LRS) were developed in this study, and their potentials in alleviating lead-induced injury to the liver and intestinal tract were evaluated in mice by oral administration for 4 weeks. As results, oral intake of lead acetate (150 mg/kg body weight per day) caused more than 50 times and 100 times lead accumulation in blood and the liver, respectively. Liver function was seriously damaged by the lead exposure, which is indicated as the significantly increased lipid accumulation in the liver, enhanced markers of liver function injury in serum, and occurrence of oxidative stress in liver tissues. Serious injury in intestinal tract was also found under lead exposure, as shown by the decrease of intestinal microbiota diversity and occurrence of oxidative stress. Except the lead content in blood and the liver were lowered by 52% and 58%, respectively, oral administration of Se-LRS protected all the other lead-induced injury markers to the normal level. By the comparison with the effects of normal L. rhamnosus SHA113 and the SeNPs isolated from Se-LRS, high protective effects of Se-LRS can be explained as the extremely high efficiency to promote lead excretion via feces by forming insoluble mixture. These findings illustrate the developed selenium-enriched L. rhamnosus can efficiently protect the liver and intestinal tract from injury by lead.

Although many toxicological studies on pesticides and nanoparticles have been conducted, it is not clear whether nanoparticles will increase the toxicity of pesticides. In this study, we chose imidacloprid (IMI) as a representative pesticide, and explored the influence of ZnO NPs on the toxic effect of IMI. In addition, we studied the bioaccumulation of IMI in mice. Using biochemical index analysis, liver histopathological analysis, non-targeted metabolomics, and LC/MS analysis, we found that ZnO NPs increased the toxicity of IMI, which may be related to the increase in IMI bioaccumulation in mice. In addition, we used intestinal histopathological analysis, RT-qPCR, and 16sRNA sequencing to find that the disturbance of the gut microbiota and the impaired intestinal barrier caused by ZnO NPs may be the reason for the increase in IMI bioaccumulation. In summary, our results indicate that ZnO NPs disrupted the intestinal barrier and enhanced the bioaccumulation of IMI, and therefore increased the toxicity of IMI in mice. Our research has deepened the toxicological insights between nanomaterials and pesticides.

Diazinon is a common organophosphate pesticide widely used to control parasitic infections in agriculture. Excessive use of diazinon can have adverse effects on the environment and aquatic animal health. In the present study, the toxic effects of diazinon on the histology, antioxidant, innate immune and intestinal microbiota community composition of crucian carp (Carassius auratus gibelio) were investigated. The results showed that diazinon at the tested concentration (300 μg/L) induced gill and liver histopathological damages. Hepatic total superoxide dismutase (T-SOD), catalase (CAT), and glutathione S-transferase (GST) activities significantly decreased (P < 0.05) by 32.47%, 65.33% and 37.34%, respectively. However, the liver tissue malondialdehyde (MDA) content significantly (P < 0.05) increased by 138.83%. The 300 μg/L diazinon significantly (P < 0.05) downregulated the gene expression of TLR4, MyD88, NF-kB p100 and IL-8 but had no significant effect TNF-α (P = 0.8239). In addition, the results demonstrated that diazinon exposure could affect the intestinal microbiota composition and diversity. Taken together, the results of this study indicated that diazinon exposure can cause damage to crucian carp, induce histopathological damage in gill and liver tissues, oxidative stress in the liver, and innate immune disorders and alter intestinal microbiota composition and diversity.

To identify the role of gut microbiota in human health risk assessment, the bioaccessibility of heavy metals in 14 soil samples were determined in simulated gastrointestinal fluids. Compared to the small intestinal phase, the bioaccessibility values of the colon phase varied, either increased by 3.5-fold for As, by 2.2-fold for Cr, and by 1.6-fold for Ni, or reduced by 4.4-fold for Cu, respectively. The colon incubation with adult gut microbiota yielded higher bioaccessibility value of As (1.3 times) and Fe (3.4 times) than that of the child in most soil samples. Colon bioaccessibility was about 60% greater of Cd for the adult and 30% higher of Cr for the child. Congruent data on the bioaccessibility of Cu and Ni was observed. In addition, correlation analysis indicated that in vitro bioaccessibility was primarily related to total concentrations of heavy metals in soils, followed by soil pH and active Fe/Mn oxide. Significantly, risk assessment calculated based on colon bioaccessibility indicated that the target hazard quotient (THQ > 1) of As was presented in 3 soil samples for the adult (1.05–3.35) and in 9 soil samples for the child (1.06–26.93). The hazard index (HI) of the child was 4.00 on average, greater than that of the adult (0.62), primarily due to the contribution of As and Cd. It suggested non-carcinogenic risks are likely to occur in children through typical hand-to-mouth behavior. The adjustment of colon bioaccessibility will result in more accurate risk assessment of human exposure to heavy metals from oral ingestion of contaminated soils.