Studying the Exposome to Understand the Environmental Determinants of Complex Liver Diseases

Cheung, Angela; Walker, Douglas I.; Juran, Brian D.; Miller, Gary W.; Lazaridis, Konstantinos N.

doi:10.1002/hep.31028

Cited by 19 publications

(11 citation statements)

References 33 publications

(71 reference statements)

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“…However, gut microbiome taxonomic data is typically over-dispersed and zero-inflated (Knight et al 2012). There is no gold standard for statistical analysis of EWAS data, and it is not clear how a list of statistically significant associations can be translated to information usable for public health policies (Cheung et al 2020). In our study, more than 50% of the datapoints were equal to 0 for 612 species out of the 724 detected.…”

Section: Discussionmentioning

confidence: 99%

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

Mesnage

Rce

et al. 2021

Preprint

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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.

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Section: Discussionmentioning

confidence: 99%

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

Mesnage

Rce

et al. 2021

Preprint

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“…These results bolster the need for more comprehensive documentation of exposure (i.e., the "exposome"). [66] This is the first study to demonstrate VC-induced tumorigenesis at concentrations that are currently considered safe. In summary, the data indicate that VC sensitizes the liver to other stressors (e.g., WD), involving dysregulation of metabolic pathways, an enrichment of genes for ribosomal processes, and changes to the epitranscriptomic pattern.…”

Section: The Enhancement Of Hcc By Vc Exposure Leads To a Unique Epit...mentioning

confidence: 91%

Western diet unmasks transient low-level vinyl chloride exposure-induced tumorigenesis; potential role of the (epi-)transcriptome

Liu

Bannister

et al. 2022

Preprint

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Background & Aims: Vinyl chloride (VC) monomer is a volatile organic compound commonly used in industry to produce polyvinyl chloride (PVC). At high exposure levels, VC causes liver cancer and toxicant-associated steatohepatitis. However, lower exposure levels (i.e., < regulatory exposure limits) that do not directly damage the liver, enhance injury caused by Western diet (WD). Although these lower exposure levels are considered 'safe,' it is unknown if the long-term impact of transient low-concentration VC enhances the risk of liver cancer development. Low-concentration VC is especially a concern given that fatty liver disease is in and of itself a risk factor for the development of liver cancer. Methods: C57Bl/6J mice were fed WD or control diet (CD) for 1 year. During the first 12 weeks of feeding only, mice were also exposed to VC via inhalation at sub-regulatory limit concentrations (<1 ppm) or air for 6 hours/day, 5 days/week. Results: Feeding WD for 1 year caused significant hepatic injury, including steatohepatitis and moderate fibrosis, which was exacerbated by VC. Additionally, VC increased the number of tumors which ranged from moderately to poorly differentiated hepatocellular carcinoma (HCC). Transcriptomic analysis demonstrated VC-induced changes in metabolic but also ribosomal processes. Epitranscriptomic analysis showed a VC-induced shift of the modification pattern that has been associated with metabolic disease, mitochondrial dysfunction, and cancer. Conclusions: These data indicate that VC sensitizes the liver to other stressors (e.g., WD), resulting in enhanced tumorigenesis. These data raise concerns about a potential interaction between VC exposure and WD. Furthermore, it also emphasizes that current safety restrictions may be insufficient to account for other factors that can influence hepatotoxicity.

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“…Clearly, the liver is exposed to an even larger spectrum of stressors. 15 Indeed, in addition to the relatively direct exposure to dietary contaminants, the liver is also exposed to contaminants with different entry points, i.e.…”

Section: The Liver Exposomementioning

confidence: 99%

Expanding the liver exposome: Should hepatologists care about air pollution?

Colombo

Barouki

2022

Journal of Hepatology

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Studying the Exposome to Understand the Environmental Determinants of Complex Liver Diseases

Cited by 19 publications

References 33 publications

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

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

Western diet unmasks transient low-level vinyl chloride exposure-induced tumorigenesis; potential role of the (epi-)transcriptome

Expanding the liver exposome: Should hepatologists care about air pollution?

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