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Steves, C.

Publications and source records attributed to Steves, C..

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Impacts of dietary exposure to pesticides on faecal microbiome metabolism in adult twins

Concerns have been raised as to whether the consumption of foodstuffs contaminated with pesticides can contribute to the development of chronic human diseases by affecting microbial community function in the gut. We provide the first associations between urinary pesticide excretion and the composition and function of the faecal microbiome in 65 twin pairs in the UK. Biomonitoring of exposure to 186 common insecticide, herbicide, or fungicide residues showed the presence of pyrethroid and/or organophosphorus insecticide residues in all urine samples, while the herbicide glyphosate was found in 45% of individuals. Other pesticides such as DEET, imidacloprid or dithiocarbamate fungicides were less frequently detected. While the geographic location or the rural/urban environment had no influence on pesticide urinary excretion, food frequency questionnaires showed that DMTP levels, a metabolite of organophosphates, was higher with increased consumption of fruit and vegetables. Multivariable association between urinary pesticide excretion and faecal microbial composition and function were determined with shotgun metagenomics and metabolomics. A total of 34 associations between pesticide residues concentrations and faecal metabolite concentrations were detected. Glyphosate excretion was positively associated to an 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 mammalian 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. Our results highlight the need for future interventional studies to understand effects of pesticide exposure on the gut microbiome and possible health consequences.

pharmacology and toxicology↗

Host genetic and environmental factors shape the human gut resistome

BackgroundUnderstanding and controlling the spread of antimicrobial resistance is one of the greatest challenges of modern medicine. To this end many efforts focus on characterising the human resistome or the set of antibiotic resistance determinants within the microbiome of an individual. Aside from antibiotic use, other host environmental and genetic factors that may shape the resistome remain relatively underexplored. MethodsUsing gut metagenome data from 250 TwinsUK female twins, we quantified known antibiotic resistance genes to estimate gut microbiome antibiotic resistance potential for 41 types of antibiotics and resistance mechanisms. Using heritability modelling, we assessed the influence of host genetic and environmental factors on the gut resistome. We then explored links between gut resistome, host health and specific environmental exposures using linear mixed effect models adjusted for age, BMI, alpha diversity and family structure. ResultsWe considered gut microbiome antibiotic resistance to 21 classes of antibiotics, for which resistance genes were detected in over 90% of our population sample. Using twin modelling, we estimated that on average about 25% of resistome variability could be attributed to host genetic influences. Greatest heritability estimates were observed for resistance potential to acriflavine (70%), dalfopristin (51%), clindamycin (48%), aminocoumarin (48%) and the total score summing across all antibiotic resistance genes (38%). As expected, the majority of resistome variability was attributed to host environmental factors specific to an individual. We compared antibiotic resistance profiles to multiple environmental exposures, lifestyle and health factors. The strongest associations were observed with alcohol and vegetable consumption, followed by high cholesterol medication and antibiotic usage. Overall, inter-individual variation in host environment showed modest associations with antibiotic resistance profiles, and host health status had relatively minor signals. ConclusionOur results identify host genetic and environmental influences on the human gut resistome. The findings improve our knowledge of human factors that influence the spread of antibiotic resistance genes and may contribute towards helping to attenuate it.

microbiology↗