Dataset Information

Low-dose exposure of glyphosate-based herbicides disrupt the urine metabolome and its interaction with gut microbiota.

ABSTRACT: Glyphosate-based herbicides (GBHs) can disrupt the host microbiota and influence human health. In this study, we explored the potential effects of GBHs on urinary metabolites and their interactions with gut microbiome using a rodent model. Glyphosate and Roundup (equal molar for glyphosate) were administered at the USA glyphosate ADI guideline (1.75 mg/kg bw/day) to the dams and their pups. The urine metabolites were profiled using non-targeted liquid chromatography-high resolution mass spectrometry (LC-HRMS). Our results found that overall urine metabolite profiles significantly differed between dams and pups and between female and male pups. Specifically, we identified a significant increase of homocysteine, a known risk factor of cardiovascular disease in both Roundup and glyphosate exposed pups, but in males only. Correlation network analysis between gut microbiome and urine metabolome pointed to Prevotella to be negatively correlated with the level of homocysteine. Our study provides initial evidence that exposures to commonly used GBH, at a currently acceptable human exposure dose, is capable of modifying urine metabolites in both rat adults and pups. The link between Prevotella-homocysteine suggests the potential role of GBHs in modifying the susceptibility of homocysteine, which is a metabolite that has been dysregulated in related diseases like cardiovascular disease or inflammation, through commensal microbiome.

SUBMITTER: Hu J

PROVIDER: S-EPMC7864973 | biostudies-literature | 2021 Feb

REPOSITORIES: biostudies-literature

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Low-dose exposure of glyphosate-based herbicides disrupt the urine metabolome and its interaction with gut microbiota.

Hu Jianzhong J Lesseur Corina C Miao Yu Y Manservisi Fabiana F Panzacchi Simona S Mandrioli Daniele D Belpoggi Fiorella F Chen Jia J Petrick Lauren L

Scientific reports 20210205 1

Glyphosate-based herbicides (GBHs) can disrupt the host microbiota and influence human health. In this study, we explored the potential effects of GBHs on urinary metabolites and their interactions with gut microbiome using a rodent model. Glyphosate and Roundup (equal molar for glyphosate) were administered at the USA glyphosate ADI guideline (1.75 mg/kg bw/day) to the dams and their pups. The urine metabolites were profiled using non-targeted liquid chromatography-high resolution mass spectrom ...[more]

PMID: 33547360

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Project description:Exposure to anthropogenic chemicals may indirectly compromise animal health by perturbing the gut microbiota. For example, the widely used herbicide glyphosate can affect the microbiota of honey bees, reducing the abundance of beneficial bacterial species that contribute to immune regulation and pathogen resistance. Previous studies have not addressed how this impact depends on concentration, duration of exposure, or stage of microbiota establishment. Worker bees acquire their microbiota from nestmates early in adult life, when they can also be exposed to chemicals collected by foragers or added to the hives. Here, we investigated how the gut microbiota of honey bees is affected by different concentrations of glyphosate and compared the effects with those caused by tylosin, an antibiotic commonly used to treat hives. We treated newly emerged workers at the stage at which they acquire the microbiota and also workers with established gut microbiota. Treatments consisted of exposure to sucrose syrup containing glyphosate in concentrations ranging from 0.01?mM to 1.0?mM or tylosin at 0.1?mM. Based on 16S rRNA amplicon sequencing and quantitative PCR (qPCR) determination of abundances, glyphosate perturbed the gut microbiota of honey bees regardless of age or period of exposure. Snodgrassella alvi was the most affected bacterial species and responded to glyphosate in a dose-dependent way. Tylosin also perturbed the microbiota, especially at the stage of acquisition, and the effects differed sharply from the effects of glyphosate. These findings show that sublethal doses of glyphosate (0.04 to 1.0?mM) and tylosin (0.1?mM) affect the microbiota of honey bees.IMPORTANCE As is true of many animal species, honey bees depend on their gut microbiota for health. The bee gut microbiota has been shown to regulate the host immune system and to protect against pathogenic diseases, and disruption of the normal microbiota leads to increased mortality. Understanding these effects can give broad insights into vulnerabilities of gut communities, and, in the case of honey bees, could provide information useful for promoting the health of these economically critical insects, which provide us with crop pollination services as well as honey and other products. The bee gut microbiota is acquired early in adult life and can be compromised by antibiotics and other chemicals. The globally used weed killer glyphosate was previously found to impact the gut microbiota of honey bees following sustained exposure. In the present study, we address how this impact depends on concentration, duration of exposure, and stage of community establishment. We found that sublethal doses of glyphosate reduce the abundance of beneficial bacteria and affect microbial diversity in the guts of honey bees, regardless of whether exposure occurs during or after microbiota acquisition. We also compared the effects of glyphosate to those of tylosin, an antibiotic used in beekeeping, and observed that tylosin effects diverge from those caused by glyphosate and are greater during microbiota acquisition. Such perturbations are not immediately lethal to bees but, depending on exposure level, can decrease survivorship under laboratory conditions.

Project description:Honey bees are important agricultural pollinators that rely on a specific gut microbiota for the regulation of their immune system and defense against pathogens. Environmental stressors that affect the bee gut microbial community, such as antibiotics and glyphosate, can indirectly compromise bee health. Most of the experiments demonstrating these effects have been done under laboratory conditions with pure chemicals. Here, we investigated the oral and topical effects of various concentrations of glyphosate in a herbicide formulation on the honey bee gut microbiota and health under laboratory and field conditions. Under all of these conditions, the formulation, dissolved in sucrose syrup or water, affected the abundance of beneficial bacteria in the bee gut in a dose-dependent way. Mark-recapture experiments also demonstrated that bees exposed to the formulation were more likely to disappear from the colony, once reintroduced after exposure. Although no visible effects were observed for hives exposed to the formulation in field experiments, challenge trials with the pathogen Serratia marcescens, performed under laboratory conditions, revealed that bees from hives exposed to the formulation exhibited increased mortality compared with bees from control hives. In the field experiments, glyphosate was detected in honey collected from exposed hives, showing that worker bees transfer xenobiotics to the hive, thereby extending exposure and increasing the chances of exposure to recently emerged bees. These findings show that different routes of exposure to glyphosate-based herbicide can affect honey bees and their gut microbiota.IMPORTANCE The honey bee gut microbial community plays a vital role in immune response and defense against opportunistic pathogens. Environmental stressors, such as the herbicide glyphosate, may affect the gut microbiota, with negative consequences for bee health. Glyphosate is usually sprayed in the field mixed with adjuvants, which enhance herbicidal activity. These adjuvants may also enhance undesired effects in nontargeted organisms. This seems to be the case for glyphosate-based herbicide on honey bees. As we show in this study, oral exposure to either pure glyphosate or glyphosate in a commercial herbicide formulation perturbs the gut microbiota of honey bees, and topical exposure to the formulation also has a direct effect on honey bee health, increasing mortality in a dose-dependent way and leaving surviving bees with a perturbed microbiota. Understanding the effects of herbicide formulations on honey bees may help to protect these important agricultural pollinators.

Project description:Glyphosate is the most commonly used herbicide around the world, which led to its accumulation in the environment and consequent ubiquitous human exposure. Glyphosate is marketed in numerous glyphosate-based herbicide formulations (GBHs) that include co-formulants to enhance herbicidal effect of the active ingredient, but are declared as inert substances. However, these other ingredients can have biologic activity on their own and may interact with the glyphosate in synergistic toxicity. In this study, we focused to compare the cytogenetic effect of the active ingredient glyphosate and three marketed GBHs (Roundup Mega, Fozat 480, and Glyfos) by investigating cytotoxicity with fluorescent co-labeling and WST-1 cell viability assay as well as genotoxicity with cytokinesis block micronucleus assay in isolated human mononuclear white blood cells. Glyphosate had no notable cytotoxic activity over the tested concentration range (0-10,000 μM), whereas all the selected GBHs induced significant cell death from 1,000 μM regardless of metabolic activation (S9). Micronucleus (MN) formation induced by glyphosate and its formulations at sub-cytotoxic concentrations (0-100 μM) exhibited a diverse pattern. Glyphosate caused statistically significant increase of MN frequency at the highest concentration (100 μM) after 20-h exposure. Contrarily, Roundup Mega exerted a significant genotoxic effect at 100 μM both after 4- and 20-h exposures; moreover, Glyfos and Fozat 480 also resulted in a statistically significant increase of MN frequency from the concentration of 10 μM after 4-h and 20-h treatment, respectively. The presence of S9 had no effect on MN formation induced by either glyphosate or GBHs. The differences observed in the cytotoxic and genotoxic pattern between the active principle and formulations confirm the previous concept that the presence of co-formulants in the formulations or the interaction of them with the active ingredient is responsible for the increased toxicity of herbicide products, and draw attention to the fact that GBHs are still currently in use, the toxicity of which rivals that of POEA-containing formulations (e.g., Glyfos) already banned in Europe. Hence, it is advisable to subject them to further comprehensive toxicological screening to assess the true health risks of exposed individuals, and to reconsider their free availability to any users.

Dataset Information

Low-dose exposure of glyphosate-based herbicides disrupt the urine metabolome and its interaction with gut microbiota.

Publications

Low-dose exposure of glyphosate-based herbicides disrupt the urine metabolome and its interaction with gut microbiota.

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