Previous studies have suggested that pesticide exposure and gut microbiome alterations are associated with gestational diabetes mellitus (GDM) risk. Understanding the complex interactive effect of these factors on GDM is essential. In a cohort of 852 pregnant women, we assessed pesticide levels in serum and analyzed the gut microbiota using 16S rRNA and shotgun metagenomic sequencing. We explored the interactions between pesticides and gut microbiota, assessed their roles in GDM development, and proposed a predictive model based on identified biomarkers. We identified an environmental risk score (ERS), denoting the pesticide mixture level significantly associated with GDM, with the gut microbiota, particularly involving the Dorea branch, playing a crucial mediating role. In addition, we found an interactive effect of pesticide exposure and gut microbiota on GDM risk. Notably, low Prevotella enrichment combined with high ERS arisen from pesticide levels led to a 10.36-fold increased GDM risk. The identified pesticide and gut microbial biomarkers achieved high predictive accuracy for GDM (AUC: 0.833, 95% CI: 0.748-0.918). Collectively, maternal pesticide exposure may induce disrupted microbiome-dependent glycemic alteration, necessitating future assessment of clinical implications. Potential GDM markers can serve as targets for therapeutic intervention caused by pesticides, leading to prevention.

Aryl phosphate esters have been detected throughout the natural environment and in human blood samples, making it important to determine the health risks associated with exposure to triphenyl phosphate (TPHP) and its metabolite diphenyl phosphate (DPHP). Here, C57BL/6J male mice were exposed to TPHP or DPHP for 12 weeks at estimated daily intake doses of 0.1 and 7 μg/kg bw/day. TPHP intake affected the levels of short-chain fatty acids and bile acids in the gut, enhancing the production of 29 medium- and long-chain fatty acids in the liver by 3.72-fold and significantly increasing hepatic lipid and cholesterol levels. Metabolomic and molecular analysis confirmed that elevated liver cholesterol levels persisted after an 8 week recovery period. Gut microbiota-dependent cholesterol alterations were the toxic end points observed in TPHP-fed mice, as supported by the results of fecal microbiota transplantation. In DPHP-fed mice, serotonergic and glutamatergic synapses were simultaneously altered in the liver and intestine, corresponding to the reduction of five brain neurotransmitters (15.4-60.8%). Decreased liver carbohydrate levels and insulin resistance were observed in the DPHP-fed mice. These results suggest that TPHP and DPHP affect metabolism via different toxic modes, mediated through the gut-liver axis, providing novel insights into the mechanisms of organophosphate-ester-mediated metabolic disruption.

Pesticides can modulate gut microbiota composition, but their specific effects on it remain largely elusive. In our study, we show that pesticides inhibit or promote the growth of various gut microbial species and can be accumulated to prolong their presence in the host. Pesticide exposure also induces significant alterations in gut bacterial metabolism, as reflected by changes in hundreds of metabolites. We generate a pesticide-gut microbiota-metabolite network that not only reveals pesticide-sensitive gut bacteria species but also reports specific metabolic changes in 306 pesticide-gut microbiota pairs. Using an in vivo mouse model, we further demonstrate the interactions of a representative pesticide-gut microbiota pair and verify the inflammation-inducing effects of pesticide exposure on the host, mediated by microbially dysregulated lipid metabolism. Taken together, our findings generate a comprehensive atlas of pesticide-gut microbiota-metabolite interactions atlas and shed light on the molecular mechanisms by which pesticides affect host health via gut microbiota-modulated metabolism.

Numerous epidemiological studies have found that pesticide exposure is associated with the incidence of type 2 diabetes (T2D); however, the underlying mechanisms remain unknown. DNA methylation may play a role in this process.

To identify the genes associated with pesticide exposure and T2D by reviewing the current literature.

We systematically searched PubMed and Embase for relevant studies that examined the association between pesticide exposure and DNA methylation, and studies on DNA methylation and T2D through January 15, 2024.

We identified six genes (Alu, CABLES1, CDH1, PDX1, PTEN, PTPRN2) related to pesticide exposure and T2D. We also suggested future research directions to better define the role of DNA methylation in the association between pesticide exposure and T2D.

DNA methylation of specific genes may play a vital role in the association between pesticide exposure and T2D.

Arsenic (As), a naturally occurring element with unique properties, has been recognized as the largest mass poisoning in the world by the World Health Organization (WHO). Approximately 200 million people worldwide are exposed to toxic levels of arsenic due to natural and anthropogenic activities. This widespread exposure necessitates a deeper understanding of microbe-arsenic interactions and their potential influence on host exposure and health risks. It is a major causative factor for metabolic diseases, including diabetes. Arsenic exposure has been linked to dysfunction in various cell types and tissues, notably affecting pancreatic islet cells. Numerous mechanisms have been identified to be responsible for arsenic exposure under both in vitro and in vivo conditions. These mechanisms contribute to the regulation of processes underlying diabetes etiology, such as glucose-stimulated insulin secretion from pancreatic beta cells. Unlike other toxic elements, arsenic undergoes metabolism by living organisms, including microbes, plants, and animals. Other toxic elements like Lead (Pb) and mercury (Hg) are generally not metabolized in the same way as Arsenic in microbes, plants and animals. In this review, we strive to initiate a dialogue by reviewing known aspects of microbe-arsenic interactions and placing it in the context of the potential for influencing host exposure and health risks. This review provides an up-to-date insight into arsenic metabolism by the human body and its associated microbiota, as well as the deciphered molecular pathways linking the different species of arsenic in the etiology of diabetes. Additionally, the future perspectives of mitigation and detoxification of arsenic in translational medicine and limitations in current scenarios are discussed. The comprehensive review presented here underscores the importance of exploring the complex interplay between arsenic metabolism, host-microbiota interactions, and their implications on glucose homeostasis and metabolic diseases. It emphasizes the need for continued research to develop effective strategies for mitigating arsenic-related health risks and fostering better translational medicine approaches.

Plastic polymers pose a significant challenge due to their resistance to degradation, resulting in their persistent accumulation in the environment and exacerbating a critical environmental concern. Urgent innovation and novel management technologies are essential to tackle this issue. Plastic biodegradation, distinguished by its environmentally friendly and safe attributes, has garnered substantial attention as a viable solution. Insects are pivotal in this process, utilizing their gut microbes to facilitate plastic degradation. The enzymatic action within the digestive tracts of diverse insect hosts and their microbial symbionts contributes to the breakdown of these polymers. This comprehensive review delves into the current landscape and strategies aimed at combating plastic pollution, with a specific focus on the involvement of insects such as mealworms (Tenebrio molitor Linnaeus), superworms (Zophobas atratus Blanchard), greater wax moths (Galleria mellonella Linnaeus), and various other insect species in the degradation of plastics. This review explores the different insects involved in plastic degradation, the mechanisms by which insects degrade plastics and delineates the characteristics of resultant degradable products. Furthermore, it investigates the future potential for plastic degradation by insects and examines the prospective developmental pathways for degradable plastics. Ultimately, this review provides an array of solutions by using various insects to pervasive the issue of plastic pollution.

Non-communicable diseases (NCDs) are the leading cause of morbidity and mortality worldwide. These conditions have numerous health consequences and significantly impact patients' lifestyles. Effective long-term treatment is essential since NCDs are irreversible. Therefore, primary healthcare must be both exclusive and of the highest quality, ensuring comprehensive care. The primary goal should be to improve quality of life with a focus on patients, families, and communities, as most of these diseases can be prevented and controlled, although not cured. Several factors have been linked to individual health, including social, cultural, and economic aspects, lifestyle, and certain environmental factors, including work, that can have positive or negative effects. More of these variables may contribute to the onset of NCDs, which are defined by their chronic nature, propensity for prolongation, and generally slow rate of progression. Examples of NCDs include hypertension, type 2 diabetes (T2D), dyslipidemia, and fatty liver disease linked to metabolic dysfunction. The onset of these diseases has been associated with an imbalance in certain microbial niches, such as the gut, which hosts billions of microorganisms performing multiple metabolic functions, such as the production of metabolites like bile acids (BAs), short-chain fatty acids (SCFAs), and trimethylamine N-oxide (TMAO). Therefore, lifestyle changes and personal habits can significantly impact the gut microbiota (GM), potentially preventing chronic diseases associated with metabolism. NCDs are highly prevalent worldwide, prompting increased attention to strategies for modifying the intestinal microbiota (IM). Approaches such as probiotics, prebiotics, synbiotics, and fecal transplantation (FMT) have demonstrated improvements in the quality of life for individuals with these conditions. Additionally, lifestyle changes and the adoption of healthy habits can significantly impact IM and may help prevent chronic diseases related to metabolism. Therefore, the main aim of this review is to analyze and understand the importance of microbiota intervention in the prevention of non-communicable diseases. R3:A1.

Brown adipose tissue (BAT) activation is an emerging target for obesity treatments due to its thermogenic properties stemming from its ability to shuttle energy through uncoupling protein 1 (Ucp1). Recent rodent studies show how BAT and white adipose tissue (WAT) activity can be modulated to increase the expression of thermogenic proteins. Consequently, these alterations enable organisms to endure cold-temperatures and elevate energy expenditure, thereby promoting weight loss. In humans, BAT is less abundant in obese subjects and impacts of thermogenesis are less pronounced, bringing into question whether energy expending properties of BAT seen in rodents can be translated to human models. Our review will discuss pharmacological, hormonal, bioactive, sex-specific and environmental activators and inhibitors of BAT to determine the potential for BAT to act as a therapeutic strategy. We aim to address the feasibility of utilizing BAT modulators for weight reduction in obese individuals, as recent studies suggest that BAT's contributions to energy expenditure along with Ucp1-dependent and -independent pathways may or may not rectify energy imbalance characteristic of obesity.

This review delves into the escalating concern of environmental pollutants and their profound impact on human health in the context of the modern surge in global diseases. The utilisation of chemicals in food production, which results in residues in food, has emerged as a major concern nowadays. By exploring the intricate relationship between environmental pollutants and gut microbiota, the study reveals a dynamic bidirectional interplay, as modifying microbiota profile influences metabolic pathways and subsequent brain functions. This review will first provide an overview of potential exposomes and their effect to gut health. This paper is then emphasis the connection of gut brain function by analysing microbiome markers with neurotoxicity responses. We then take pesticide as example of exposome to elucidate their influence to biomarkers biosynthesis pathways and subsequent brain functions. The interconnection between neuroendocrine and neuromodulators elements and the gut-brain axis emerges as a pivotal factor in regulating mental health and brain development. Thus, manipulation of gut microbiota function at the onset of stress may offer a potential avenue for the prevention and treatment for mental disorder and other neurodegenerative illness.

Malathion® is a persistent organophosphate pesticide used against biting and chewing insects on vegetables. It is a difficult-to-remove surface contaminant of vegetables and contaminates surface and ground water and soils. Malathion® is only partially water soluble, but use of detergent carriers makes adhering Malathion® residues difficult to subsequently remove. Magnetically treated water (MTW) successfully removed Malathion® from Chinese Kale (Brassica oleracea L.), meeting Maximum Residue Load (MRL) standards. Samples were soaked in MTW for 30 min prior to detection with GC/MS/MS, 98.5±3.02% of Malathion® was removed after washing by MTW. Removal by simple washing was only ≈42±1.2% which was not nearly sufficient to meet MRL criteria.

Organophosphorus pesticides (OP) have been associated with various human health conditions. Animal experiments and in-vitro models suggested that OP may also affect the gut microbiota. We examined associations between ambient chronic exposure to OP and gut microbial changes in humans.

We recruited 190 participants from a community-based epidemiologic study of Parkinson's disease living in a region known for heavy agricultural pesticide use in California. Of these, 61% of participants had Parkinson's disease and their mean age was 72 years. Microbiome and predicted metagenome data were generated by 16S rRNA gene sequencing of fecal samples. Ambient long-term OP exposures were assessed using pesticide application records combined with residential addresses in a geographic information system. We examined gut microbiome differences due to OP exposures, specifically differences in microbial diversity based on the Shannon index and Bray-Curtis dissimilarities, and differential taxa abundance and predicted Metacyc pathway expression relying on regression models and adjusting for potential confounders.

OP exposure was not associated with alpha or beta diversity of the gut microbiome. However, the predicted metagenome was sparser and less evenly expressed among those highly exposed to OP (p = 0.04). Additionally, we found that the abundance of two bacterial families, 22 genera, and the predicted expression of 34 Metacyc pathways were associated with long-term OP exposure. These pathways included perturbed processes related to cellular respiration, increased biosynthesis and degradation of compounds related to bacterial wall structure, increased biosynthesis of RNA/DNA precursors, and decreased synthesis of Vitamin B1 and B6.

In support of previous animal studies and in-vitro findings, our results suggest that ambient chronic OP pesticide exposure alters gut microbiome composition and its predicted metabolism in humans.

Epidemiological studies have related exposure to pesticides to increased risk of diabetes. However, few studies have evaluated the health effects of mixed pesticides exposure, especially in an elderly population. Here, we utilized gas chromatography-tandem mass spectrometry to quantify the levels of 39 pesticides in 4 categories in a Chinese elderly population. Then we used general linear models to explore the association between individual pesticide exposure and type 2 diabetes mellitus (T2DM). Restricted cubic spline (RCS) models were fitted to identify potential non-linearities between those associations. Furthermore, stratified analysis by gender was conducted to explore the gender-specific associations. Finally, we used weighted quantile sum (WQS) regression, quantile-based g computation (qgcomp), and Bayesian kernel machine regression (BKMR) to evaluate the effects of mixed exposure to 39 pesticides. The results showed that exposure to pesticides was associated with high risk of T2DM, with β-Hexachlorocyclohexane (β-BHC) and oxadiazon being the most significant independent contributors, which was pronounced among elderly women. Moreover, the association of β-BHC and oxadiazon with T2DM was linear. These indicated that it is an urgent need to take practical measures to control these harmful pesticides.

Rural residents are exposed to both particulate and gaseous pesticides in the indoor-outdoor nexus in their daily routine. However, previous personal exposure assessment mostly focuses on single aspects of the exposure, such as indoor or gaseous exposure, leading to severe cognition bias to evaluate the exposure risks. In this study, residential dust and silicone wristbands (including stationary and personal wearing ones) were used to screen pesticides in different phases and unfold the hidden characteristics of personal exposure via indoor-outdoor nexus in intensive agricultural area. Mento-Carlo Simulation was performed to assess the probabilistic exposure risk by transforming adsorbed pesticides from wristbands into air concentration, which explores a new approach to integrate particulate (dust) and gaseous (silicone wristbands) pesticide exposures in indoor and outdoor environment. The results showed that particulate pesticides were more concentrated in indoor, whereas significantly higher concentrations were detected in stationary outdoor wristbands (p < 0.05). Carbendazim and chlorpyrifos were the most frequently detected pesticides in dust and stationary wristbands. Higher pesticide concentration was found in personal wristbands worn by farmers, with the maximum value of 2048 ng g-1 for difenoconazole. Based on the probabilistic risk assessment, around 7.1 % of farmers and 2.6 % of bystanders in local populations were potentially suffering from chronic health issues. One third of pesticide exposures originated mainly from occupational sources while the rest derived from remoting dissipation. Unexpectedly, 43 % of bystanders suffered the same levels of exposure as farmers under the co-existence of occupational and non-occupational exposures. Differed compositions of pesticides were found between environmental samples and personal pesticide exposure patterns, highlighting the need for holistic personal exposure measurements.

The extensive use of pesticides may cause acute and chronic intoxication. Therefore, this study aimed to reveal the associations between pesticide exposure and serum markers for stroke risk factors in farmers. A cross-sectional study was conducted with farmers, who used chemical pesticides in Seloprojo Village, Ngablak District, Magelang Regency, Central Java Province, Indonesia. A questionnaire containing demographics, pesticide use, and aspects related to work was employed. Measurements of serum cholesterol, uric acid, glucose, cholinesterase, and fibrinogen levels were also conducted. Of the 106 subjects, 31 (29.2%) used organophosphates as chemical pesticides. There was a significant difference between organophosphate and nonorganophosphate groups in plasma fibrinogen levels. The organophosphate group had higher levels of fibrinogen (292.29 ± 67.56 mg/dL) than the non-organophosphate group (255.24 ± 38.90 mg/dL). Of the studied risk factors for stroke, there is a significant association between organophosphate exposure and increased plasma fibrinogen levels.

Glyphosate-based herbicides (GBHs) are used extensively around the world and have become the leading agrochemicals. However, study about the association between glyphosate exposure and the risk of diabetes mellitus (DM) is scarce. This study used 4 years of NHANES data (2013-2016) to further investigate the association. A total of 2535 participants were enrolled in this cross-sectional study. The baseline information and urinary glyphosate levels in diabetic and non-diabetic groups were compared. Using multivariable logistic regression mode, we explored the association between both the continuous and categorical forms of urinary glyphosate and DM risk. Further subgroup analyses based on categorical covariates were also conducted. Urinary glyphosate levels were 0.42 ng/ml in participants with diabetes and 0.34 ng/ml in participants without diabetes (P < 0.05). As a continuous variable, ln-transformed urinary glyphosate was significantly associated with an increased risk of DM in the most adjusted model (OR 1.28, 95% CI 1.03-1.57). However, the association was not significant in the most adjusted categorical model (P > 0.05).In further subgroup analyses, the associations remained significant in several subgroups. This study provides new evidence that glyphosate exposure was associated with a higher risk of diabetes in the American general adult population.

Malathion and diazinon are pesticides commonly used in agriculture to avoid insects that damage crops; however, they may cause impairment to the male genital system of exposed humans. The present work carried out a systematic review of the literature concerning the primary studies that assessed the reproductive effects resulting from male rats and mice exposed to malathion or diazinon. The search for articles was performed on the databases PubMed, LILACS, Scopus, and SciELO, using different combinations of the search terms "malathion," "diazinon," "mice," "rats," "male reproduction," "fertility," and "sperm," followed by the Boolean operators AND or OR. The results obtained indicate that both pesticides act as reproductive toxicants by reducing sperm quality, diminishing hormonal concentrations, inducing increased oxidative stress, and provoking histopathological damage in reproductive organs. Then, the exposure to malathion and diazinon may provoke diminished levels of testosterone by increasing acetylcholine stimulation in the testis through muscarinic receptors, thus, providing a reduction in steroidogenic activity in Leydig cells, whose effect is related to lower levels of testosterone in rodents, and consequently, it is associated with decreased fertility. Considering the toxic effects on the male genital system of rodents and the possible male reproductive toxicity in humans, it is recommended the decreased use of these pesticides and their replacement for others that show no or few toxic effects for non-target animals.

Children are exposed to various environmental organic and inorganic contaminants with effects on health outcomes still largely unknown. Many matrices (e.g., blood, urine, nail, hair) have been used to characterize exposure to organic and inorganic contaminants. The sampling of feces presents several advantages; it is non-invasive and provides a direct evaluation of the gut microbiome exposure to contaminants. The gut microbiome is a key factor in neurological development through the brain-gut axis. Its composition and disturbances can affect the neurodevelopment of children. Characterization of children exposure to contaminants is often performed on vulnerable populations (e.g., from developing countries, low-income neighborhoods, and large urban centers). Data on the exposure of children from middle-class, semi-urban, and mid-size populations to contaminants is scarce despite representing a significant fraction of the population in North America. In this study, 73 organics compounds from different chemical classes and 22 elements were analyzed in 6 years old (n = 84) and 10 years old (n = 119) children's feces from a middle-class, semi-urban, mid-size population cohort from Eastern Canada. Results show that 67 out of 73 targeted organics compounds and all elements were at least detected in one child's feces. Only caffeine (97% & 80%) and acetaminophen (28% & 48%) were detected in more than 25% of the children's feces, whereas all elements besides titanium were detected in more than 50% of the children.

The human gut microbiota can be potentially disrupted due to exposure of various environmental contaminants, including pesticides. These contaminants enter into non-target species in multiple ways and cause potential health risks. The gut microbiota-derived metabolites have a significant role in maintaining the host's health by regulating metabolic homeostasis. An imbalance in this homeostasis can result in the development of various diseases and their pathogenesis. Pesticides have hazardous effects on the host's gut microbiota, which is evident in a few recent studies. Therefore, there is an urgent need to explore the effect of pesticide on gut microbiota-mediated metabolic changes in the host, which may provide a better understanding of pesticide-induced toxicity. The present review summarizes the pesticide-induced effects on gut microbiota, which in turn, induces changes in the release of their secondary metabolites that could lead to various host health effects.

Herein, we report a simple, low-temperature, ecofriendly synthesis of graphene oxide nanosheets (GONs). Graphite powder was treated with KMnO₄ and a concentrated H₂SO₄/H₃PO₄ mixture to synthesize GONs. The effects of various reaction conditions such as reaction time, temperature, amounts of cleaving agents (H₂SO₄/H₃PO₄), and oxidant (KMnO₄) were investigated. The synthesized GONs were examined by various techniques in order to investigate their characteristics. The best results of the synthesized GONs were observed at 35 °C within 10 h of reaction time having 8:2 ratios of H₂SO₄/H₃PO₄ acid mixture. The main absorption peak in the UV-vis spectra of GONs was at 258 nm, which is due to the π-π* transition of the atomic CC bonds. The existence of stretching vibrations of C꞊O, O-H, C-H, and C-O in the Fourier transform infrared (FTIR) spectra verified the formation of GONs. Presence of a sharp peak at 2θ = 10° with an interlayer spacing distance of 0.88 nm in the observed XRD pattern revealed that the synthesized GONs were totally oxidized and that the interlayer spacing increased. The morphological investigations confirmed the formation of ultrathin, transparent, curly, and homogenous GONs. The synthesized GONs were applied as an adsorbent for the rapid uptake of four different pesticides viz.; Profenofos, Ethion, Cypermethrin, Thiamethoxam (TMX) from the pesticides spiked water samples. About 86% adsorption of Profenofos + Cypermethrin, and 50% adsorption of ethion and thiamethoxam took place within 20 min in presence of 10 mg GONs. In addition to this, the prepared GONs were tested for the antibacterial activity against four bacterial strains by agar well diffusion method. The synthesized GONs provide a significant inhibition for gram -positive (Bacillus subtilis, and Staphylococcus aureus) and gram-negative (Escherichia coli and Pseudomonas aeruginosa) bacterial strains. Moreover, the radical scavenging activities (RSA) of GONs were also checked and compared with Gallic acid as a standard. The obtained RSA of GONs was 60% in comparison to the 80% as of the standard Gallic acid at 1000 μg/mL concentration.

Liver disease is the only major chronic disease and mortality is increasing. Earlier detection of liver fibrosis can reduce progression to cirrhosis and hepatocellular carcinoma. Many studies have reported an increased prevalence in liver fibrosis among adults in urban regions but there are few data in physically active rural populations without attributable metabolic risk factors. This aim of this study is to investigate the prevalence of abnormal liver functions tests (LFTs) and liver fibrosis among adults in a rural population.

This cross-sectional study included observations from KMCH-NNCD-II (2017) study (n = 907) from a farming village, Nallampatti, located in South India. We assessed lifestyle (occupation, tobacco use and alcohol consumption using AUDIT-C questionnaire), markers for metabolic diseases (obesity, hypertension, diabetes, hypercholesterolemia), LFTs and markers for hepatitis viruses B and C. 901 participants had transient elastography to assess fibrosis. Participants with abnormal LFTs and significant liver fibrosis (F2-F4) underwent additional liver screening (caeruloplasmin, iron studies and autoimmune hepatitis panel). Multiple logistic regression analyses were performed to understand the association of liver fibrosis with lifestyle and metabolic risk factors after adjustment for co-variates.

Significant liver fibrosis (F2-F4) was observed in 14.4%, and cirrhosis in 0.8%. There was an association of liver fibrosis with abnormal LFTs but no association between alcohol consumption, viral hepatitis, hepatic liver screening and liver fibrosis. Among metabolic risk factors, no association was observed for hypertension and hypercholesterolemia but diabetes [OR - 3.206 (95% CI: 1.792 - 5.736)], obesity [1.987 (1.341 - 2.944)] and metabolic syndrome [2.539 (1.680 - 3.836)] showed association with significant liver fibrosis (F2-F4) after adjustment for confounding factors.

Our results suggest that the prevalence of liver fibrosis in rural population is similar to urban counterparts. The association of metabolic risk factors with liver fibrosis in physically active rural population warrants further investigations in future studies.

This study is funded by KMCH Research Foundation, India.

Insulin resistance is an underlying condition prior to the development of several diseases, including type 2 diabetes, cardiovascular diseases, cognitive impairment, and cerebrovascular complications. Organophosphates (OPs) are one of several factors thought to induce insulin resistance. Previous studies showed that the exposure to OPs pesticides induced insulin resistance through the impairment of hepatic glucose metabolism, pancreatic damage, and disruption of insulin signaling of both adipose tissues and skeletal muscles. Several studies reported possible mechanisms associated with OPs-induced insulin resistance in different models in in vivo studies including those in adult animals, obese animals, and offspring models, as well as in clinical studies. In addition, pharmacological interventions in OPs-induced insulin resistance have been previously investigated. This review aims to summarize and discuss all the evidence concerning OPs-induced insulin resistance in different models including in vitro, in vivo and clinical studies. The interventions of OPs-induced insulin resistance are also discussed. Any contradictory findings also considered. The information from this review will provide insight for possible therapeutic approaches to OPs-induced insulin resistance in the future.

The gut microbiota contributes to diverse aspects of host physiology, ranging from immunomodulation to drug metabolism. Changes in the gut microbiota composition are associated with various diseases as well as with the response to medications. It is therefore important to understand how different lifestyle and environmental factors shape gut microbiota composition. Beyond the commonly considered factor of diet, small-molecule drugs have recently been identified as major effectors of the microbiota composition. Other xenobiotics, such as environmental or chemical pollutants, can also impact gut bacterial communities. Here, we review the mechanisms of interactions between gut bacteria and antibiotics, host-targeted drugs, natural food compounds, food additives and environmental pollutants. While xenobiotics can impact bacterial growth and metabolism, bacteria in turn can bioaccumulate or chemically modify these compounds. These reciprocal interactions can manifest in complex xenobiotic-microbiota-host relationships. Our Review highlights the need to study mechanisms underlying interactions with pollutants and food additives towards deciphering the dynamics and evolution of the gut microbiota.

Dietary habits have a profound influence on the metabolic activity of gut microorganisms and their influence on health. Concerns have been raised as to whether the consumption of foodstuffs contaminated with pesticides can contribute to the development of chronic disease by affecting the gut microbiome. We performed the first pesticide biomonitoring survey of the British population, and subsequently used the results to perform the first pesticide association study on gut microbiome composition and function from the TwinsUK registry.

Dietary exposure of 186 common insecticide, herbicide, or fungicide residues and the faecal microbiome in 65 twin pairs in the UK was investigated. We evaluated if dietary habits, geographic location, or the rural/urban environment, are associated with the excretion of pesticide residues. The composition and metabolic activity of faecal microbiota was evaluated using shotgun metagenomics and metabolomics respectively. We performed a targeted urine metabolomics analysis in order to evaluate whether pesticide urinary excretion was also associated with physiological changes.

Pyrethroid and/or organophosphorus insecticide residues were found in all urine samples, while the herbicide glyphosate was found in 53% of individuals. Food frequency questionnaires showed that residues from organophosphates were higher with increased consumption of fruit and vegetables. A total of 34 associations between pesticide residue concentrations and faecal metabolite concentrations were detected. Glyphosate excretion was positively associated with an overall increased bacterial species richness, as well as to fatty acid metabolites and phosphate levels. The insecticide metabolite Br2CA, reflecting deltamethrin exposure, was positively associated with the phytoestrogens enterodiol and enterolactone, and negatively associated with some N-methyl amino acids. Urine metabolomics performed on a subset of samples did not reveal associations with the excretion of pesticide residues.

The consumption of conventionally grown fruit and vegetables leads to higher ingestion of pesticides with unknown long-term health consequences. Our results highlight the need for future dietary intervention studies to understand effects of pesticide exposure on the gut microbiome and possible health consequences.

Environmental chemicals can alter gut microbial community composition, known as dysbiosis. However, the gut microbiota is a highly dynamic system and its functions are still largely underexplored. Likewise, it is unclear whether xenobiotic exposure affects host health through impairing host-microbiota interactions. Answers to this question not only can lead to a more precise understanding of the toxic effects of xenobiotics but also can provide new targets for the development of new therapeutic strategies. Here, we aim to identify the major challenges in the field of microbiota-exposure research and highlight the need to exam the health effects of xenobiotic-induced gut microbiota dysbiosis in host bodies. Although the changes of gut microbiota frequently co-occur with the xenobiotic exposure, the causal relationship of xenobiotic-induced microbiota dysbiosis and diseases is rarely established. The high dynamics of the gut microbiota and the complex interactions among exposure, microbiota, and host, are the major challenges to decipher the specific health effects of microbiota dysbiosis. The next stage of study needs to combine various technologies to precisely assess the xenobiotic-induced gut microbiota perturbation and the subsequent health effects in host bodies. The exposure, gut microbiota dysbiosis, and disease outcomes have to be causally linked. Many microbiota-host interactions are established by previous studies, including signaling metabolites and response pathways in the host, which may use as start points for future research to examine the mechanistic interactions of exposure, gut microbiota, and host health. In conclusion, to precisely understand the toxicity of xenobiotics and develop microbiota-based therapies, the causal and mechanistic links of exposure and microbiota dysbiosis have to be established in the next stage study.

High toxicity of dimethoate requires efficient ways for detoxification and removal of its residues in contaminated environments. Microbial remediation is a process that utilizes the degradation potential of microbes to provide a cost-effective and reliable approach for pesticide abatement. For this purpose, a dimethoate-degrading bacterium Brucella sp. was isolated from a contaminated agricultural soil sample in Multan, Pakistan. This isolate was found to tolerate up to 100 ppm of dimethoate in minimal salt medium and was further evaluated for plant growth-promoting traits. The strain gave positive results for amylase, ammonia, and catalase production, while other traits such as indole acetic acid production and potassium solubilization were also confirmed. Thus, the strain could play an important role for plant nutrient transmission in the plant rhizosphere. Optimization of growth parameters (i.e., pH and temperature) depicted the potential of PS4 to be best tolerating dimethoate, with maximum cell density at λ 600 nm. Optimum pH and temperature for growth were found to be 6 and 35 °C, respectively. Based on optimization results as well as different attributes, the rhizospheric bacterial isolate PS4 was further subjected to a batch degradation experiment under different concentrations of dimethoate (25, 50, 75, and 100 ppm). This promising dimethoate-degrading isolate was found to degrade 83% of dimethoate (at 100 ppm) within a period of 7 days. In addition, it degraded 88% of dimethoate at 50 ppm, indicating that the bacterial isolate utilized dimethoate solely as a source of energy. The strain followed the first order reaction kinetics, depicting its dependence on dimethoate as energy and carbon source. Molecular profiling further supported its role in plant growth promotion and multi-stress tolerance. This research showed that Brucella sp. is capable of degrading dimethoate, and therefore, it would be useful in the investigation of novel bioremediation techniques at pesticide-polluted sites.

Organophosphate is a commonly used pesticide in the agricultural sector. The main action of organophosphate focuses on acetylcholinesterase inhibition, and it therefore contributes to acute cholinergic crisis, intermediate syndrome and delayed neurotoxicity. From sporadic case series to epidemiologic studies, organophosphate has been linked to hyperglycemia and the occurrence of new-onset diabetes mellitus. Organophosphate-mediated direct damage to pancreatic beta cells, insulin resistance related to systemic inflammation and excessive hepatic gluconeogenesis and polymorphisms of the enzyme governing organophosphate elimination are all possible contributors to the development of new-onset diabetes mellitus. To date, a preventive strategy for organophosphate-mediated new-onset diabetes mellitus is still lacking. However, lowering reactive oxygen species levels may be a practical method to reduce the risk of developing hyperglycemia.

The Contaminants of Emerging Concern (CECs), including pesticides, have been a trending topic and Brazil is the country with the highest usage of pesticides worldwide. This study aimed to measure the presence of pesticide residues in the water from different sources in the city of Porto Alegre. We analyzed 55 samples from drinking water treatment plants, public water sites, and sewage treatment plants from winter 2018 to summer 2020 by solid-phase extraction and high-performance liquid chromatography-electrospray ionization mass spectrometry. Among 184 pesticides evaluated, 107 matched validation criteria (linearity, trueness, accuracy, repeatability, reproducibility) and 15 of them were detected in different water samples, including seven insecticides, five antifungals, and three herbicides, with a wide range of toxicity levels and noticeable seasonal differences. For the worst-case scenario evaluation, 20 out of 22 (90.9%) samples exceeded the Risk Quotient of 1. The sum of pesticide concentrations exceeded 100 ng L^-1 in 66.7% of samples in February 19 and in 75% of samples in February 20 and the total pesticide concentration has reached the worrisome mark of 1615 and 954.96 ng L^-1 respectively. Therefore, our results make evident the need to promote public policies to achieve better water quality monitoring. PRACTITIONER POINTS: Among 184 pesticides evaluated, 107 matched validation criteria (linearity, trueness, accuracy, repeatability, reproducibility). A total of 55 different water samples were analyzed, and 15 pesticides were detected and five quantified. For the worst-case scenario evaluation, 20 out of 21 samples exceeded the Risk Quotient of 1 on Feb/20. The pesticide concentrations sum exceeded 100 ng L^-1 in 66.7% of samples on February 19 and in 75% of samples on February 20. It is mandatory to improve water monitoring to guide the development of public policies concerning its quality.

Diazinon is an organophosphorus pesticide widely used to control cabbage insects, cotton aphids and underground pests. The continuous application of diazinon in agricultural activities has caused both ecological risk and biological hazards in the environment. Diazinon can be degraded via physical and chemical methods such as photocatalysis, adsorption and advanced oxidation. The microbial degradation of diazinon is found to be more effective than physicochemical methods for its complete clean-up from contaminated soil and water environments. The microbial strains belonging to Ochrobactrum sp., Stenotrophomonas sp., Lactobacillus brevis, Serratia marcescens, Aspergillus niger, Rhodotorula glutinis, and Rhodotorula rubra were found to be very promising for the ecofriendly removal of diazinon. The degradation pathways of diazinon and the fate of several metabolites were investigated. In addition, a variety of diazinon-degrading enzymes, such as hydrolase, acid phosphatase, laccase, cytochrome P450, and flavin monooxygenase were also discovered to play a crucial role in the biodegradation of diazinon. However, many unanswered questions still exist regarding the environmental fate and degradation mechanisms of this pesticide. The catalytic mechanisms responsible for enzymatic degradation remain unexplained, and ecotechnological techniques need to be applied to gain a comprehensive understanding of these issues. Hence, this review article provides in-depth information about the impact and toxicity of diazinon in living systems and discusses the developed ecotechnological remedial methods used for the effective biodegradation of diazinon in a contaminated environment.

There has been a huge increase in diabetes and its associated cardiovascular complications over the last decade, predominantly in the middle- and low-income countries. In these countries, the majority live in rural areas. The Rural Epidemiology of Diabetes in South India (REDSI) study was aimed to analyze the prevalence of diabetes, cardiovascular risk factors, and its complications in rural farming and non-farming villages in Tamil Nadu, South India. A research survey on the prevalence of self-reported diabetes, cardiovascular risk factors (age, sex, obesity, hypertension, hypercholesterolemia, alcohol and tobacco use) and agricultural occupational exposure was executed among 106,111 people from 61 villages in the state of Tamil Nadu, South India, during 2015-2018. Overall, we observed a diabetes prevalence of 11.9% in rural South India. A nearly two-fold higher prevalence of diabetes was observed among the farming community (15.0%) compared to that among the non-farming population (8.7%). Logistic regression analyses revealed a strong association with agrochemical exposure (P < 0.0001) and diabetes prevalence among rural farming people. Our survey indicates a high prevalence of diabetes in rural South India particularly among the farming community. This survey in conjunction with other epidemiological and experimental studies raises the need for understanding the etiology of diabetes and other cardiovascular risk factors in rural communities.

Chlorinated paraffins (CPs) are environmental pollutants of emerging concern. Long-chain CPs (LCCPs) are considered of lesser concern than other CPs in food due to their lower accumulation in most organisms. However, LCCPs have been shown to accumulate preferentially in birds. We used ultrahigh-performance liquid chromatography combined with electrospray ionization Orbitrap mass spectrometry (UPLC-ESI-Orbitrap MS) to analyze CPs (C_10-26Cl_4-12) in tissues of free-range hens, their feed, and local soils. Feed was found to be the main source of CP intake. The CP carbon chain length had little impact on their absorption. C₁₈-CPs were excreted in preference to C₁₃-CPs by laying. The metabolic elimination rates of CPs (0.2 μg/mL) estimated using chicken liver microsomes were in the order C₁₂Cl₆ (91%) > C₁₂Cl₈ (57%) > C₁₈Cl₆ (12%) > C₁₈Cl₈ (6%). CPs with longer carbon chains accumulated preferentially in muscle and adipose tissues, and the accumulation of specific carbon chain lengths was related to the content and composition of different CPs in the intake source.

Since the surge of microbiome research in the last decade, many studies have provided insight into the causes and consequences of changes in the gut microbiota. Among the multiple factors involved in regulating the microbiome, exogenous factors such as diet and environmental chemicals have been shown to alter the gut microbiome significantly. Although diet substantially contributes to changes in the gut microbiome, environmental chemicals are major contaminants in our food and are often overlooked. Herein, we summarize the current knowledge on major classes of environmental chemicals (bisphenols, phthalates, persistent organic pollutants, heavy metals, and pesticides) and their impact on the gut microbiome, which includes alterations in microbial composition, gene expression, function, and health effects in the host. We then discuss health-related implications of gut microbial changes, which include changes in metabolism, immunity, and neurological function.

Marilyn Silva. Retired from a career in toxicology and risk assessment. Increased childhood and adult obesity are associated with chlorpyrifos (CPF), an organophosphate pesticide. Cannabis (Δ9Tetrahydrocannabinol: Δ9THC) use has increased globally with legalization. CPF applications on cannabis crops lacks federally regulated tolerances and may pose health risks through exposure during development and in adulthood. Both CPF and Δ9THC affect the endocannabinoid system (eCBS), a regulator of appetite, energy balance, and gut microbiota, which, if disrupted, increases risk for obesity and related diseases. CPF inhibits eCB metabolism and Δ9THC is a partial agonist/antagonist at the cannabinoid receptor (CB1R). Effects of each on obesogenic parameters were examined via literature search. Male rodents with CPF exposure showed increased body weights, dysbiosis, inflammation and oxidative stress, potentially associated with increased eCBs acting through the gut-microbiota-adipose-brain regulatory loop. Δ9THC generally decreased body weights via partial agonism at the CB1R, lowering levels of eCBs. Dysbiosis and/or oxidative stress associated inflammation occurred with CPF, but these parameters were not tested with Δ9THC. Database deficiencies included limited endpoints to compare between chemicals/age-groups, inter-study variables (dose ranges, dosing vehicle, rodent strain, treatment duration, etc.). CPF and Δ9THC were not tested together, but human co-chemical effects would depend on exposure ratio, subject age, exposure duration, and health status, among others. An overriding concern is that both chemicals are well-documented developmental neurotoxins in addition to their low dose effects on energy balance. A co-exposure risk assessment is warranted with increased use and lack of federal CPF regulation on cannabis.

Rovral® is a fungicide used to control pests that affect various crops and little is known regarding its effects on embryonic development of amniotes. Thus, this study aimed to determine the influence of Rovral® during chicken organogenesis using acute in ovo contamination. Fertilized eggs were inoculated with different concentrations of Rovral® (100, 300, 500 or 750 µl/ml), injected into the egg's air chamber. After 7 days, embryos were examined for possible malformations, staging, weight and mortality. Subsequently, head, trunk, limbs and eyes were measured for morphometry and asymmetry. For blood analysis, eggs were treated with 300 µl/ml Rovral® and glucose, presence of micronuclei and erythrocyte nuclei abnormalities determined. Treatments with Rovral® affected the mortality rate in a concentration-dependent manner. LC₅₀ value was found to be 596 µl/ml which represents 397-fold higher than the recommended concentration for use. Rovral® produced several malformations including hemorrhagic, ocular and cephalic abnormalities. No significant changes were observed in body weight, staging, body measurements, symmetry and glucose levels of live embryos, which indicates this fungicide presents low toxicity under the analyzed conditions. Changes in erythrocyte nuclei were noted; however significant difference was observed only for presence of binucleated erythrocytes. It is important to point out that possibly more significant changes may have occurred at lower concentrations through chronic contamination. Therefore, caution is needed in the use of this fungicide, since it presents teratogenic and mutagenic potential.

South Asia has emerged rapidly as an epicentre of non-communicable diseases (NCDs) specifically diabetes and cardiovascular diseases. The prevalence rate, risk factors and aetiology of NCDs in different socio-demographic settings are not clearly understood. This study was performed to assess the prevalence of diabetes and atherosclerosis and their risk factors in urban, sub-urban and rural communities of South India.

Three communities [Nallampatti (rural), Thadagam (sub-urban) and Kalapatti (urban)] in South India were selected for participation in the KMCH-NCD Studies. Study volunteers were administered a detailed questionnaire, underwent anthropometric measurements, clinical measurements including blood pressure, glycated haemoglobin (HbA_1c ), non-fasting lipid profile and serum creatinine. Carotid intima-media thickness was measured using B-mode ultrasound. Multiple logistic regression analyses were performed to understand the association of risk factors with diabetes and atherosclerosis.

A total of 2976 native participants, ≥20 years of age were screened. The prevalence of diabetes was 16%, 26% and 23% respectively in the rural, sub-urban and urban study populations. Association of obesity with diabetes was observed in only urban population while hypertension and dyslipidaemia showed association in both urban and semi-urban populations. Association of diabetes with atherosclerosis was observed in urban and semi-urban populations. Hypertension in semi-urban and obesity and dyslipidaemia in urban population showed association with atherosclerosis.

Diabetes and atherosclerosis burden reported in the three different communities were higher than previous reports, especially in rural and sub-urban regions. No traditional risk factor is identified to be associated with prevalence of diabetes and atherosclerosis in rural population. These findings suggest an urgent need for investigation into the role of non-traditional risk factors like environmental or occupational exposures may help to better understand the aetiology of diseases in non-urbanized communities.

Organophosphorus pesticide (OP) residues present in food can be metabolized into diethylphosphate (DEP) in vivo. Epidemiological studies of OPs have usually focused on these metabolites, while animal studies mainly assessed the OPs. Here, we compared the health risks of a frequently detected OP, triazophos (TAP), and its major metabolite, DEP, in rats. Levels of serum lipids and, sex hormones were measured using immunoassay kits. Gut hormones and inflammatory cytokines were assessed using a multiplexing kit, and the gut microbiota was evaluated by 16S rRNA gene sequencing. After a 24-week exposure period, both TAP and DEP significantly decreased serum levels of triglycerides, cholesterol, low-density lipoprotein cholesterol, and IL-6 (p < 0.05). However, DEP exposure had a stronger effect on serum estradiol (p < 0.05) than TAP, whereas only TAP inhibited the secretion of gut hormones. Both TAP and DEP enriched the pathogenic genera Oscillibacter, Peptococcus and Paraprevotella in the gut, and TAP also enriched enteritis-related genera Roseburia and Oscillibacter, which may affect the secretion of gut hormones. These findings indicate that the use of dialkyl phosphates as markers of OPs to examine the correlations of OP exposure with diseases may only provide partial information, especially for diseases related to gut health and the endocrine system.

Many in vivo and in vitro studies have shown that pesticides can disrupt the functioning of gut microbiota (GM), which can lead to many diseases in humans. While the tests developed by the Organization of Economic Cooperation and Development (OECD) are expected to capture most apical effects resulting from GM disruptions, exclusion of GM in the risk assessment might mischaracterize hazards or overestimate/underestimate risks, especially when extrapolating results from one species to another species or population with a substantially different GM. On the other hand, direct assessment of GM-mediated effects may face challenges in identifying hazards, since not all GM perturbations will lead to human adverse effects. In this regard, reliable and validated biomarkers for common GM-mediated adverse effects may be very useful in the identification of GM-mediated pesticide toxicity. Nevertheless, proving causality of GM-mediated effects will need modifications of Bradford Hill criteria as well as Koch's postulates, which are more suitable for the "one-pathogen" paradigm. Furthermore, risk assessment of GM-mediated effects may require pesticide toxicokinetics along the gut, possibly through modeling, and the establishment of the involvement of GM in the mechanism of action (MOA) of the pesticide. Risk assessment of GM mediated effects also requires the standardization of experimental approaches as well as the establishment of microbial reference communities, since variations exist among GM in human populations.

Currently, research agenda in marine ecotoxicology is facing new challenges with the emergence of newly and complex synthetized chemicals. The study of the fate and adverse effects of toxicants remains increasingly complicated with global change events. Ecotoxicology had provided for a decades, precious scientific data and knowledge but also technical and management tools for the environmental community. Regarding those, it is necessary to update methodologies dealing with these issues such as combined effect of conventional and emergent stressors and global changes. In this point of view article, we discuss one hand the new challenges of ecotoxicology in this context, and in the other hand, the need of updating agenda and methodologies currently used in monitoring programs and finally recommendations and future research needs. Among recommendations, it could be cited the necessity to perform long-term experiments, the standardization of sentinel species and taking benefit from baseline studies and omics technologies.

Pesticides have long been used in agriculture and household treatments. Pesticide residues can be found in biological samples for both the agriculture workers through direct exposure but also to the general population by indirect exposure. There is also evidence of pesticide contamination in utero and trans-generational impacts. Whilst acute exposure to pesticides has long been associated with endocrine perturbations, chronic exposure with low doses also increases the prevalence of metabolic disorders such as obesity or type 2 diabetes. Dysmetabolism is a low-grade inflammation disorder and as such the microbiota plays a role in its etiology. It is therefore important to fully understand the role of microbiota on the genesis of subsequent health effects. The digestive tract and mostly microbiota are the first organs of contact after oral exposure. The objective of this review is thus to better understand mechanisms that link pesticide exposure, dysmetabolism and microbiota. One of the key outcomes on the microbiota is the reduced Bacteroidetes and increased Firmicutes phyla, reflecting both pesticide exposure and risk factors of dysmetabolism. Other bacterial genders and metabolic activities are also involved. As for most pathologies impacting microbiota (including inflammatory disorders), the role of prebiotics can be suggested as a prevention strategy and some preliminary evidence reinforces this axis.

Obesity is considered as a risk factor for chronic health diseases such as heart diseases, cancer and diabetes 2. Reduced physical activities, lifestyle, poor nutritional diet and genetics are among the risk factors associated with the development of obesity. In recent years, several studies have explored the link between the gut microbiome and the progression of diseases including obesity, with the shift in microbiome abundance and composition being the main focus. The alteration of gut microbiome composition affects both nutrients metabolism and specific gene expressions, thereby disturbing body physiology. Specifically, the abundance of fibre-metabolizing microbes is associated with weight loss and that of protein and fat-metabolizing bacteria with weight gain. Various internal and external factors such as genetics, maternal obesity, mode of delivery, breastfeeding, nutrition, antibiotic use and the chemical compounds present in the environment are known to interfere with the richness of the gut microbiota (GM), thus influencing weight gain/loss and ultimately the development of obesity. However, the effectiveness of each factor in potentiating the shift in microbes' abundance to result in significant changes that can lead to obesity is not yet clear. In this review, we will highlight the factors involved in shaping GM, their influence on obesity and possible interventions. Understanding the influence of these factors on the diversity of the GM and how to improve their effectiveness on disease conditions could be keys in the treatment of metabolic diseases.

Global plastic production has increased exponentially since manufacturing commenced in the 1950's, including polymer types infused with diverse additives and fillers. While the negative impacts of plastics are widely reported, particularly on marine vertebrates, impacts on microbial life remain poorly understood. Plastics impact microbiomes directly, exerting toxic effects, providing supplemental carbon sources and acting as rafts for microbial colonisation and dispersal. Indirect consequences include increased environmental shading, altered compositions of host communities and disruption of host organism or community health, hormone balances and immune responses. The isolation and application of plastic-degrading microbes are of substantial interest yet little evidence supports the microbial biodegradation of most high molecular weight synthetic polymers. Over 400 microbial species have been presumptively identified as capable of plastic degradation, but evidence for the degradation of highly prevalent polymers including polypropylene, nylon, polystyrene and polyvinyl chloride must be treated with caution; most studies fail to differentiate losses caused by the leaching or degradation of polymer monomers, additives or fillers. Even where polymer degradation is demonstrated, such as for polyethylene terephthalate, the ability of microorganisms to degrade more highly crystalline forms of the polymer used in commercial plastics appears limited. Microbiomes frequently work in conjunction with abiotic factors such as heat and light to impact the structural integrity of polymers and accessibility to enzymatic attack. Consequently, there remains much scope for extremophile microbiomes to be explored as a source of plastic-degrading enzymes and microorganisms. We propose a best-practice workflow for isolating and reporting plastic-degrading taxa from diverse environmental microbiomes, which should include multiple lines of evidence supporting changes in polymer structure, mass loss, and detection of presumed degradation products, along with confirmation of microbial strains and enzymes (and their associated genes) responsible for high molecular weight plastic polymer degradation. Such approaches are necessary for enzymatic degraders of high molecular weight plastic polymers to be differentiated from organisms only capable of degrading the more labile carbon within predominantly amorphous plastics, plastic monomers, additives or fillers.