Gut microbiome disruption altered the biotransformation and liver toxicity of arsenic in mice

Chi, Liang; Xue, Jingchuan; Tu, Pengcheng; Lai, Yunjia; Ru, Hongyu; Lü, Kun

doi:10.1007/s00204-018-2332-7

Cited by 71 publications

(43 citation statements)

References 82 publications

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“…Although it is structurally simple, it undergoes complex biotransformation and forms a series of products with different toxicity. In vitro incubation elucidated the unique metabolic role of gut microbiota and in vivo study illustrated that gut microbiota reduced arsenic load by promoting methylation and thus protected the host from hepatotoxicity of arsenic (Chi et al, 2019a). Similarly, another study also found that a stable gut microbiome was a key determinant of survival to arsenic exposure, andFaecalibacterium prausnitzii protected it (Coryell et al, 2018).…”

Section: Substances Other Than Drugsmentioning

confidence: 91%

Connecting the dots: targeting gut microbiota in drug toxicity

Luo¹,

Zhou²

2020

Preprint

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Gut microbiota has been demonstrated to have a vast influence on human health in recent decades and its role in initiating, aggravating, or ameliorating diseases is emerging. Therapeutic strategies have therefore increasingly developed by targeting gut microbial modulation. Recently, its contribution to heterogeneous toxicological responses is also gaining attention, especially in drug-induced toxicity. Oral drugs interact directly with gut microbiota within the gastrointestinal tract and a number of them elicit toxicity mediated by intestinal microbiota. Present studies focus more on the unidirectional influence of how xenobiotics disturb intestinal microbial composition and function and consequently induce altered homeostasis. However, interactions between gut microbiota and xenobiotics are bidirectional and the impact of gut microbiota on xenobiotics especially on drugs should not be neglected. Thus, in this review, we intend to focus on how gut microbiota modulates drug toxicity by highlighting gut microbiota, microbial enzyme, and metabolites to proffer references for seeking common countermeasures in coping with drug toxicity by targeting gut microbiota. Moreover, we give a hypothesis that drugs capable of inducing gut dysbiosis tend to more or less impact the gut-connected organs as evidenced by the drug-induced hepatic encephalopathy, indicating an underlying link among the gut, liver, brain, and other possible organs in drug-induced toxicity.

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Section: Substances Other Than Drugsmentioning

confidence: 91%

Connecting the dots: targeting gut microbiota in drug toxicity

Luo¹,

Zhou²

2020

Preprint

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“…An investigation of the role of the gut microbiota in arsenic metabolism, conducted in mice, showed that gut dysbiosis enhanced the toxic effects of arsenic, one way through increasing arsenic load and the other through promoting one-carbon metabolism. However, a balanced gut microbiota absorbs arsenic and promotes its methylation (Chi et al, 2019). In addition, dysbiosis may alter the expressions of some genes involved in p35 signaling and many genes involved in hepatocellular carcinoma development (Chi et al, 2019).…”

Section: Environmental Chemicals and Pollutantsmentioning

confidence: 99%

“…However, a balanced gut microbiota absorbs arsenic and promotes its methylation (Chi et al, 2019). In addition, dysbiosis may alter the expressions of some genes involved in p35 signaling and many genes involved in hepatocellular carcinoma development (Chi et al, 2019). While arsenic by itself may disturb the gut microbial community (Lu et al, 2014), Bacteroides, Clostridium, Alistipes, Bilophila, and other bacterial genera are able to methylate arsenic and can survive exposure to it owing to multiple arsenic resistance genes encoded in their genome (Yin et al, 2015;Yu et al, 2016).…”

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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“…In this study and similarly in a just recently reported study by Chi et al . (), the mouse gut microbiomes performed a bioaccumulation function, resulting in increased arsenic concentrations in mouse stool while simultaneously reducing arsenic uptake and accumulation in the mouse liver, spleen, heart and lung (Coryell et al ., ). Further, humanizing germ‐free As3mt − knockout mice (hypersensitive to arsenic) with stool homogenates from different human donors clearly demonstrated how the GIT microorganisms provide a protective measure by significantly reducing arsenic‐induced mortality, although varying between human stool donors (Coryell et al ., ).…”

Section: Arsenic and The Git Microbiomementioning

confidence: 99%

“…Arsenic-induced mouse microbiome perturbations have been related to significant changes in host serum profiles of fatty acids, phospholipids, sphingolipids, cholesterols and tryptophan (Xue et al, 2019b). Other mouse gut microbiome-related changes included downregulation of host genes encoding one-carbon and glutathione metabolisms, significantly decreased liver S-adenosylmethionine levels, and numerous genes encoding various functions associated with hepatocellular carcinoma were significantly altered (Chi et al, 2019). Arsenic exposed adult mice display higher levels of CC chemokines, and pro-inflammatory and antiinflammatory cytokine secretion in the intestine accompanied by significant changes in the gut microbiome (Gokulan et al, 2018).…”

Section: Arsenic Perturbation Of the Microbiomementioning

confidence: 99%

Arsenic and the gastrointestinal tract microbiome

McDermott

Stolz

Oremland

2020

Environ Microbiol Rep

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Summary Arsenic is a toxin, ranking first on the Agency for Toxic Substances and Disease Registry and the Environmental Protection Agency Priority List of Hazardous Substances. Chronic exposure increases the risk of a broad range of human illnesses, most notably cancer; however, there is significant variability in arsenic‐induced disease among exposed individuals. Human genetics is a known component, but it alone cannot account for the large inter‐individual variability in the presentation of arsenicosis symptoms. Each part of the gastrointestinal tract (GIT) may be considered as a unique environment with characteristic pH, oxygen concentration, and microbiome. Given the well‐established arsenic redox transformation activities of microorganisms, it is reasonable to imagine how the GIT microbiome composition variability among individuals could play a significant role in determining the fate, mobility and toxicity of arsenic, whether inhaled or ingested. This is a relatively new field of research that would benefit from early dialogue aimed at summarizing what is known and identifying reasonable research targets and concepts. Herein, we strive to initiate this dialogue by reviewing known aspects of microbe–arsenic interactions and placing it in the context of potential for influencing host exposure and health risks. We finish by considering future experimental approaches that might be of value.

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Gut microbiome disruption altered the biotransformation and liver toxicity of arsenic in mice

Cited by 71 publications

References 82 publications

Connecting the dots: targeting gut microbiota in drug toxicity

Connecting the dots: targeting gut microbiota in drug toxicity

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

Arsenic and the gastrointestinal tract microbiome

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