International audience | Antibiotics have been increasingly used over the past decades for human medicine, food-animal agriculture, aquaculture, and plant production. A significant part of the active molecules of antibiotics can be released into the environment, in turn affecting ecosystem functioning and biogeochemical processes. At lower organizational scales, these substances affect bacterial symbionts of insects, with negative consequences on growth and development of juveniles, and population dynamics. Yet, the multiple alterations of cellular physiology and metabolic processes have remained insufficiently explored in insects. We evaluated the effects of five antibiotics with different mode of action, i.e. ampicillin, cefradine, chloramphenicol, cycloheximide, and tetracycline, on the survival and ultrastructural organization of the flight muscles of newly emerged blow flies Chrysomya albiceps. Then, we examined the effects of different concentrations of antibiotics on mitochondrial protein content, efficiency of oxidative phosphorylation, and activity of transaminases (Glutamate oxaloacetate transaminase and glutamate pyruvate transaminase) and described the cellular metabolic perturbations of flies treated with antibiotics. All antibiotics affected the survival of the insects and decreased the total mitochondrial protein content in a dose-dependent manner. Ultrastructural organization of flight muscles in treated flies differs dramatically compared to the control groups and severe pathological damages/structures disorganization of mitochondria appeared. The activities of mitochondrial transaminases significantly increased with increased antibiotic concentrations. The oxidation rate of pyruvate + proline from isolated mitochondria of the flight muscles of 1-day-old flies was significantly reduced at high doses of antibiotics. In parallel, the level of several metabolites, including TCA cycle intermediates, was reduced in antibiotics-treated flies. Overall, antibiotics provoked a system-wide alteration of the structure and physiology of flight muscles of the blow fly Ch. albiceps, and may have fitness consequences at the organism level. Environmental antibiotic pollution is likely to have unwanted cascading ecological effects of insect population dynamics and community structure.

International audience | This study aims to find the interaction between ionome and metabolome profiles of Pteris vittata L., an arsenic hyperaccumulator plant, to reveal its metal tolerance mechanism. Therefore, at the Pb-Zn mining sites located in Thai Nguyen province, Vietnam, where these species dominate, soil and plant samples were collected. Their multi-element compositions were analyzed using inductively coupled plasma mass spectrometry (ICP-MS) and thus referred to as the "ionomics" approach. In parallel, the widely targeted metabolomics profiles of these plant samples were performed using liquid chromatography-tandem mass spectrometry (UPLC-QqQ-MS). Nineteen elements, including both metals and nonmetals, were detected and quantified in both tissues of thirty-five plant individuals. A comparison of these elements' levels in two tissues showed that above-ground parts accumulated more As and inorganic P, whereas Zn, Pb, and Sb were raised mostly in the under-ground samples. The partial least squares regression (PLSR) model predicting the level of each element by the whole metabolome indicated that the enhancement of flavonoids content plays an essential contribution in adaptation with the higher levels of Pb, Ag, and Ni accumulated in the aerial part, and Mn, Pb in subterranean part. Moreover, the models also highlighted the effect of Mn and Pb on the metabolic induction of adenosine derivatives in subterranean parts. At the same time, the model presented the most contribution of As to the metabolisms of the amino acids of this tissue. On those accounts, the developed integration approach linking the ionomics and metabolomics data of P. vittata improved the understanding of the molecular mechanism of hyperaccumulation characteristics and provided markers that could be targeted in future investigations.

International audience | Antibiotics have been increasingly used over the past decades for human medicine, food-animal agriculture, aquaculture, and plant production. A significant part of the active molecules of antibiotics can be released into the environment, in turn affecting ecosystem functioning and biogeochemical processes. At lower organizational scales, these substances affect bacterial symbionts of insects, with negative consequences on growth and development of juveniles, and population dynamics. Yet, the multiple alterations of cellular physiology and metabolic processes have remained insufficiently explored in insects. We evaluated the effects of five antibiotics with different mode of action, i.e. ampicillin, cefradine, chloramphenicol, cycloheximide, and tetracycline, on the survival and ultrastructural organization of the flight muscles of newly emerged blow flies Chrysomya albiceps. Then, we examined the effects of different concentrations of antibiotics on mitochondrial protein content, efficiency of oxidative phosphorylation, and activity of transaminases (Glutamate oxaloacetate transaminase and glutamate pyruvate transaminase) and described the cellular metabolic perturbations of flies treated with antibiotics. All antibiotics affected the survival of the insects and decreased the total mitochondrial protein content in a dose-dependent manner. Ultrastructural organization of flight muscles in treated flies differs dramatically compared to the control groups and severe pathological damages/structures disorganization of mitochondria appeared. The activities of mitochondrial transaminases significantly increased with increased antibiotic concentrations. The oxidation rate of pyruvate + proline from isolated mitochondria of the flight muscles of 1-day-old flies was significantly reduced at high doses of antibiotics. In parallel, the level of several metabolites, including TCA cycle intermediates, was reduced in antibiotics-treated flies. Overall, antibiotics provoked a system-wide alteration of the structure and physiology of flight muscles of the blow fly Ch. albiceps, and may have fitness consequences at the organism level. Environmental antibiotic pollution is likely to have unwanted cascading ecological effects of insect population dynamics and community structure.

Although cadmium (Cd) is a toxic heavy metal that reportedly causes liver injury, few studies have investigated biomarkers of Cd-induced liver injury. The purpose of this study is to investigate the role of bile acid (BA) in Cd-induced liver injury and determine reliable and sensitive biochemical parameters for the diagnosis of Cd-induced liver injury. In this study, 48 Sprague-Dawley rats were randomly divided into six groups and administered either normal saline or 2.5, 5, 10, 20, and 40 mg/kg/d cadmium chloride for 12 weeks. A total of 403 subjects living in either a control area (n = 135) or Cd polluted area (n = 268) of Dongdagou-Xinglong (DDGXL) cohort were included, a population with long-term low Cd exposure. The BA profiles in rats' liver, serum, caecal contents, faeces, and subjects' serum were detected using high-performance liquid chromatography-tandem mass spectrometry (HPLC–MS/MS). Changes in rats' and subjects' liver injury indices, rats' liver pathological degeneration, and rats' liver and subjects’ blood Cd levels were also measured. Cadmium exposure caused cholestasis and an increase in toxic BAs, leading to liver injury in rats. Among them, glycoursodeoxycholic acid (GUDCA), glycolithocholic acid (GLCA), taurolithocholic acid (TLCA), and taurodeoxycholate acid (TDCA) are expected to be potential biomarkers for the early detect of Cd-induced liver injury. Serum BAs can be used to assess Cd-induced liver injury as a simple, feasible, and suitable method in rats. Serum GUDCA, GLCA, TDCA, and TLCA were verified to be of value to evaluate Cd-induced liver injury and Cd exposure in humans. These findings provided evidence for screening and validation of additional biomarkers for Cd-induced liver injury based on targeted BA metabolomics.

Ambient air pollutants are well-known risk factors for childhood asthma and asthma exacerbation. It is unknown whether different air pollutants individually or jointly affect pathophysiological mechanisms of asthma. In this study, we aim to integrate transcriptome and untargeted metabolome to identify dysregulated genetic and metabolic pathways that are associated with exposures to a mixture of ambient and traffic-related air pollutants among adults with asthma history. In this cross-sectional study, 102 young adults with childhood asthma history were enrolled from southern California in 2012. Whole blood transcriptome was measured with 20,869 expression signatures, and serum untargeted metabolomics including 937 metabolites were analyzed by Metabolon, Inc. Participants’ exposures to regional air pollutants (NO₂, O₃, PM₁₀, PM₂.₅) and near-roadway air pollutants averaged at one month and one year before study visit were estimated based on residential addresses. xMWAS network analysis and joint-pathway analysis were performed to identify subnetworks and genetic and metabolic pathways that were associated with exposure to air pollutants adjusted for socio-characteristic covariates. Network analysis found that exposures to air pollutants mixture were connected to 357 gene markers and 92 metabolites. One-year and one-month averaged PM₂.₅ and NO₂ were associated with several amino acids related to serine, glycine, and beta-alanine metabolism. Lower serum levels of carnosine and aspartate, which are involved in the beta-alanine metabolic pathway, as well as choline were also associated with worse asthma control (p < 0.05). One-year and one-month averaged PM₁₀ and one-month averaged O₃ were associated with higher gene expression levels of HSPA5, LGMN, CTSL and HLA-DPB1, which are involved in antigen processing and presentation. These results indicate that exposures to various air pollutants are associated with altered genetic and metabolic pathways that affect anti-oxidative capacity and immune response and can potentially contribute to asthma-related pathophysiology.

Arsenic (As) is a highly toxic metalloid adversely affecting the environment, human health, and crop productivity. The present study assessed the synergistic effects of salinity and As on photosynthetic attributes, stomatal regulations, and metabolomics responses of the xero-halophyte Salvadora persica to decipher the As-salinity cross-tolerance mechanisms and to identify the potential metabolites/metabolic pathways involved in cross-tolerance of As with salinity. Salinity and As stress-induced significant stomatal closure in S. persica suggests an adaptive response to decrease water loss through transpiration. NaCl supplementation improved the net photosynthetic rate (by +39%), stomatal conductance (by +190%), water use efficiency (by +55%), photochemical quenching (by +37%), and electron transfer rate (54%) under As stress as compared to solitary As treatment. Our results imply that both stomatal and non-stomatal factors account for a reduction in photosynthesis under high salinity and As stress conditions. A total of 64 metabolites were identified in S. persica under salinity and/or As stress, and up-regulation of various metabolites support early As-salinity stress tolerance in S. persica by improving antioxidative defense and ROS detoxification. The primary metabolites such as polyphenols (caffeic acid, catechin, gallic acid, coumaric acid, rosmarinic acid, and cinnamic acid), amino acids (glutamic acid, cysteine, glycine, lysine, phenylalanine, and tyrosine), citrate cycle intermediates (malic acid, oxalic acid, and α-ketoglutaric acid), and most of the phytohormones accumulated at higher levels under combined treatment of As + NaCl compared to solitary treatment of As. Moreover, exogenous salinity increased glutamate, glycine, and cysteine, which may induce higher synthesis of GSH-PCs in S. persica. The metabolic pathways that were significantly affected in response to salinity and/or As include inositol phosphate metabolism, citrate cycle, glyoxylate and dicarboxylate metabolism, amino acid metabolism, and glutathione metabolism. Our findings indicate that inflections of various metabolites and metabolic pathways facilitate S. persica to withstand and grow optimally even under high salinity and As conditions. Moreover, the addition of salt enhanced the arsenic tolerance proficiency of this halophyte.

Exposure to tobacco smoke during pregnancy has been associated with a series of adverse reproductive outcomes; however, the underlying molecular mechanisms are not well-established. We conducted an untargeted metabolome-wide association study to identify the metabolic perturbations and molecular mechanisms underlying the association between cotinine, a widely used biomarker of tobacco exposure, and adverse birth outcomes. We collected early and late pregnancy urine samples for cotinine measurement and serum samples for high-resolution metabolomics (HRM) profiling from 105 pregnant women from the Atlanta African American Maternal-Child cohort (2014–2016). Maternal metabolome perturbations mediating prenatal tobacco smoke exposure and adverse birth outcomes were assessed by an untargeted HRM workflow using generalized linear models, followed by pathway enrichment analysis and chemical annotation, with a meet-in-the-middle approach. The median maternal urinary cotinine concentrations were 5.93 μg/g creatinine and 3.69 μg/g creatinine in early and late pregnancy, respectively. In total, 16,481 and 13,043 metabolic features were identified in serum samples at each visit from positive and negative electrospray ionization modes, respectively. Twelve metabolic pathways were found to be associated with both cotinine concentrations and adverse birth outcomes during early and late pregnancy, including tryptophan, histidine, urea cycle, arginine, and proline metabolism. We confirmed 47 metabolites associated with cotinine levels, preterm birth, and shorter gestational age, including glutamate, serine, choline, and taurine, which are closely involved in endogenous inflammation, vascular reactivity, and lipid peroxidation processes. The metabolic perturbations associated with cotinine levels were related to inflammation, oxidative stress, placental vascularization, and insulin action, which could contribute to shorter gestations. The findings will support the further understanding of potential internal responses in association with tobacco smoke exposures, especially among African American women who are disproportionately exposed to high tobacco smoke and experience higher rates of adverse birth outcomes.

Numerous epidemiological studies have shown a close relationship between outdoor air pollution and increased risks for cancer, infection, and cardiopulmonary diseases. However, very few studies have investigated the potential health effects of coexposure to airborne particulate matter (PM) and bioaerosols through the transmission of infectious agents, particularly under the current circumstances of the coronavirus disease 2019 pandemic. In this study, we aimed to identify urinary metabolite biomarkers that might serve as clinically predictive or diagnostic standards for relevant diseases in a real-time manner. We performed an unbiased gas/liquid chromatography-mass spectroscopy (GC/LC-MS) approach to detect urinary metabolites in 92 samples from young healthy individuals collected at three different time points after exposure to clean air, polluted ambient, or purified air, as well as two additional time points after air repollution or repurification. Subsequently, we compared the metabolomic profiles between the two time points using an integrated analysis, along with Kyoto Encyclopedia of Genes and Genomes-enriched pathway and time-series analysis. We identified 33 and 155 differential metabolites (DMs) associated with PM and bioaerosol exposure using GC/LC-MS and follow-up analyses, respectively. Our findings suggest that 16-dehydroprogesterone and 4-hydroxyphenylethanol in urine samples may serve as potential biomarkers to predict or diagnose PM- or bioaerosol-related diseases, respectively. The results indicated apparent differences between PM- and bioaerosol-associated DMs at five different time points and revealed dynamic alterations in the urinary metabolic profiles of young healthy humans with cyclic exposure to clean and polluted air environments. Our findings will help in investigating the detrimental health effects of short-term coexposure to airborne PM and bioaerosols in a real-time manner and improve clinically predictive or diagnostic strategies for preventing air pollution-related diseases.

Currently, studies on the association between per-/polyfluoroalkyl substances (PFAS) concentrations and the renal function of residents, especially teenagers, living near fluorochemical industrial plants, are relatively rare, and not all these studies suggested associations. In this cross-sectional study, 775 local teenagers (11–15 years old) were included, and serum concentrations of 18 PFAS were measured. Perfluorooctanoic acid (PFOA) was found to be the dominant PFAS with a concentration of 22.3–3310 ng/mL (mean = 191 ng/mL), accounting for 71.5–99.1% of ΣPFAS. Statistical analyses demonstrated that internal exposure of perfluoroalkyl carboxylic acids (PFCA, C8–C10) was related to the plant. In addition, the prevalence rate of chronic kidney disease (CKD) (35.0%) in the participants was relatively high. A significantly positive association was observed between the increase in PFOA concentration and increasing risk of CKD (OR = 1.741; 95% CI: 1.004, 3.088; p = 0.048) by adjusting for gender, age, body mass index (BMI), and household income. Similar positive correlation was also observed in PFHpA with CKD (OR = 1.628, 95% CI: 1.031, 2.572; p = 0.037). However, no significant correlation was observed for concentrations of other PFAS and CKD (p > 0.05). Furthermore, linear regression analyses demonstrated that none of the PFAS concentrations were significantly correlated with estimated glomerular filtration rate (eGFR) or urine albumin/urine creatinine ratio (ACR) (p > 0.05). However, a significantly negative correlation was observed between PFOA concentration and abnormal ACR (β = −0.141, 95% CI: −0.283, 0.001; p = 0.048) after stratifying by CKD. Sensitivity analyses further confirmed these results. This cross-sectional study is the first, to our knowledge, to investigate the association between PFAS concentrations and renal function in teenagers living near a Chinese industrial plant. Further prospective and metabonomic studies are needed to interpret the results and clarify the biological mechanisms underlying this association.

Plastic particles, which are formed from routinely used plastics and their fragments, have become a new pollutant raising widespread concern about their potential effects. Several studies have been conducted to examine their toxicity, but the effects of nano-sized plastic fragments on freshwater organisms remain largely unclear and need to be further investigated. In this study, larval tilapia were first exposed to 100 nm polystyrene nanoparticles (PS-NPs, 20 mg/L) for seven days and then returned to freshwater without PS-NPs for another seven days in order to determine the toxic effects of PS-NPs at both transcriptomic and metabolomic levels. A total of 203 significantly changed metabolites, and 2,152 differentially expressed unigenes were identified between control and PS-NP treatment groups, control and recovery groups, as well as treatment and recovery groups. Our data suggested that PS-NPs induced abnormal metabolism of glycolipids, energy, and amino acids in tilapia after short-term exposure. Additionally, PS-NPs caused disturbed signaling, as suggested by the transcriptomic results. Different transcriptomic and metabolomic levels between the treatment group and recovery group indicated a persistent impact of PS-NPs on tilapia. The presence of adhesion molecule-related differentially expressed genes (DEGs) suggested that PS-NPs might cause early inflammatory responses. Notably, the detection of chemical stimulus involved in the sensory perception of smell was the most severely impacted biological process. Our work systemically studied the ecotoxicity of nano-sized plastics in aquatic creatures at the molecular and genetic levels, serving as a basis for future investigations on the prevention and treatment of such pollutants.