Flux, Impact, and Fate of Halogenated Xenobiotic Compounds in the Gut

Atashgahi, Siavash; Shetty, Sudarshan A.; Smidt, Hauke; Vos, Willem M. de

doi:10.3389/fphys.2018.00888

Cited by 55 publications

(28 citation statements)

References 161 publications

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“…In addition, there are reciprocal interactions between POPs in feces and gut microbiota [37]. Therefore, the change of gut microbiota could be one possible mechanism linking POPs and colorectal cancer because the gut microbiota is strongly associated with colorectal carcinogenesis by multiple mechanisms [38].…”

Section: Discussionmentioning

confidence: 99%

Association of colorectal polyps and cancer with low-dose persistent organic pollutants: A case-control study

et al. 2018

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Background Low-dose persistent organic pollutants (POPs) have recently been linked to immunosenescence, a key mechanism in carcinogenesis, as well as many aging-related chronic diseases. Since feces are the main excretion route of POPs, the large intestine is a potential target organ for these pollutants. We performed a case-control study to evaluate whether exposure to low-dose POPs is related to the risk of colorectal polyps and cancer. Methods A total of 277 participants were recruited from one hospital: 99 cancer patients, 102 polyp patients, and 76 control subjects. As typical examples of POPs, we measured the serum concentrations of organochlorine pesticides (OCPs) and polychlorinated biphenyls (PCBs). Results Across the tertiles of the summary measure of POPs, the adjusted odds ratios (ORs) of colorectal polyps and cancer were 2.8 (1.2-6.8) (P trend = 0.01) and 3.0 (1.0-8.8) (P trend = 0.02), respectively, for subjects in the highest tertile. When OCPs and PCBs were analyzed separately, OCPs were linked to an increased risk of both polyps and cancer; the adjusted ORs were 2.3 (0.9-5.7) (P trend = 0.05) for polyps and 3.6 (1.1-11.8) (P trend < 0.01) for cancer. However, PCBs were only significantly associated with a high risk of polyps but not cancer; the adjusted OR was 2.8 (1.2-6.6) (P trend = 0.01). Conclusion Chronic exposure to low-dose POPs may be associated with an increased risk of colorectal polyps and cancer. Our findings suggest the carcinogenic potential of strong lipophilic

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Section: Discussionmentioning

confidence: 99%

Association of colorectal polyps and cancer with low-dose persistent organic pollutants: A case-control study

et al. 2018

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“…They possess a negative impact on the gut microbiota, changing the Firmicutes-to-Bacteroidetes ratio to a dysbiotic one, and hence exposing humans to obesity or immune system perturbations. The gut microbiome is capable of nitroreductive metabolism and reductive dehalogenation for organohalogens (Atashgahi et al, 2018). One of these compounds, 2,4-D (2,4-dichlorophenoxyacetic acid), is one of the most commonly used herbicides around the world (Peterson et al, 2017).…”

Section: Environmental Chemicals and Pollutantsmentioning

confidence: 99%

Toxicomicrobiomics: The Human Microbiome vs. Pharmaceutical, Dietary, and Environmental Xenobiotics

et al. 2020

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The harmful impact of xenobiotics on the environment and human health is being more widely recognized; yet, inter-and intraindividual genetic variations among humans modulate the extent of harm, mostly through modulating the outcome of xenobiotic metabolism and detoxification. As the Human Genome Project revealed that host genetic, epigenetic, and regulatory variations could not sufficiently explain the complexity of interindividual variability in xenobiotics metabolism, its sequel, the Human Microbiome Project, is investigating how this variability may be influenced by human-associated microbial communities. Xenobioticmicrobiome relationships are mutual and dynamic. Not only does the human microbiome have a direct metabolizing potential on xenobiotics, but it can also influence the expression of the host metabolizing genes and the activity of host enzymes. On the other hand, xenobiotics may alter the microbiome composition, leading to a state of dysbiosis, which is linked to multiple diseases and adverse health outcomes, including increased toxicity of some xenobiotics. Toxicomicrobiomics studies these mutual influences between the everchanging microbiome cloud and xenobiotics of various origins, with emphasis on their fate and toxicity, as well the various classes of microbial xenobiotic-modifying enzymes. This review article discusses classic and recent findings in toxicomicrobiomics, with examples of interactions between gut, skin, urogenital, and oral microbiomes with pharmaceutical, foodderived, and environmental xenobiotics. The current state and future prospects of toxicomicrobiomic research are discussed, and the tools and strategies for performing such studies are thoroughly and critically compared.

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“…ese evidences suggest that a similar mechanism could predispose to the gut inflammation state and formation of colorectal polyps. Moreover, xenobiotics, as persistent organic pollutants, can interact with gut microbiota modifying its structure and inducing carcinogenesis of colorectum [63]. OCPs are absorbed in the small intestine and accumulate mainly in the adipose tissue, from which they join the bloodstream [64], whereas PCBs are mainly removed from the body in feces [48].…”

Section: Environmental Factors Environmental Influences Alonementioning

confidence: 99%

Molecular Aspects of Colorectal Adenomas: The Interplay among Microenvironment, Oxidative Stress, and Predisposition

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Catalano

Curia

2020

BioMed Research International

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The development of colorectal cancer (CRC) is a multistep process initiated by a benign polyp that has the potential to evolve into in situ carcinoma through the interactions between environmental and genetic factors. CRC incidence rates are constantly increased for young adult patients presenting an advanced tumor stage. The majority of CRCs arise from colonic adenomas originating from aberrant cell proliferation of colon epithelium. Endoscopic polypectomy represents a tool for early detection and removal of polyps, although the occurrence of cancers after negative colonoscopy shows a significant incidence. It has long been recognized that the aberrant regulation of Wingless/It (Wnt)/β-Catenin signaling in the pathogenesis of colorectal cancer is supported by its critical role in the differentiation of stem cells in intestinal crypts and in the maintenance of intestinal homeostasis. For this review, we will focus on the development of adenomatous polyps through the interplay between renewal signaling in the colon epithelium and reactive oxygen species (ROS) production. The current knowledge of molecular pathology allows us to deepen the relationships between oxidative stress and other risk factors as lifestyle, microbiota, and predisposition. We underline that the chronic inflammation and ROS production in the colon epithelium can impair the Wnt/β-catenin and/or base excision repair (BER) pathways and predispose to polyp development. In fact, the coexistence of oxidative DNA damage and errors in DNA polymerase can foster C>T transitions in various types of cancer and adenomas, leading to a hypermutated phenotype of tumor cells. Moreover, the function of Adenomatous Polyposis Coli (APC) protein in regulating DNA repair is very important as therapeutic implication making DNA damaging chemotherapeutic agents more effective in CRC cells that tend to accumulate mutations. Additional studies will determine whether approaches based on Wnt inhibition would provide long-term therapeutic value in CRC, but it is clear that APC disruption plays a central role in driving and maintaining tumorigenesis.

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Flux, Impact, and Fate of Halogenated Xenobiotic Compounds in the Gut

Cited by 55 publications

References 161 publications

Association of colorectal polyps and cancer with low-dose persistent organic pollutants: A case-control study

Association of colorectal polyps and cancer with low-dose persistent organic pollutants: A case-control study

Toxicomicrobiomics: The Human Microbiome vs. Pharmaceutical, Dietary, and Environmental Xenobiotics

Molecular Aspects of Colorectal Adenomas: The Interplay among Microenvironment, Oxidative Stress, and Predisposition

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