Gut Microbiome Phenotypes Driven by Host Genetics Affect Arsenic Metabolism Original paper

Researched by:

  • Divine Aleru ID
    Divine Aleru

    User avatarI am a biochemist with a deep curiosity for the human microbiome and how it shapes human health, and I enjoy making microbiome science more accessible through research and writing. With 2 years experience in microbiome research, I have curated microbiome studies, analyzed microbial signatures, and now focus on interventions as a Microbiome Signatures and Interventions Research Coordinator.

    Read More

September 15, 2025

  • Metals
    Metals

    OverviewHeavy metals play a significant and multifaceted role in the pathogenicity of microbial species. Their involvement can be viewed from two primary perspectives: the toxicity of heavy metals to microbes and the exploitation of heavy metals by microbial pathogens to establish infections and evade the host immune response. Understanding these aspects is critical for both […]

  • Microbes
    Microbes

    Microbes, short for microorganisms, are tiny living organisms that are ubiquitous in the environment, including on and inside the human body. They play a crucial role in human health and disease, functioning within complex ecosystems in various parts of the body, such as the skin, mouth, gut, and respiratory tract. The human microbiome, which is […]

Researched by:

  • Divine Aleru ID
    Divine Aleru

    User avatarI am a biochemist with a deep curiosity for the human microbiome and how it shapes human health, and I enjoy making microbiome science more accessible through research and writing. With 2 years experience in microbiome research, I have curated microbiome studies, analyzed microbial signatures, and now focus on interventions as a Microbiome Signatures and Interventions Research Coordinator.

    Read More

Last Updated: 2025-09-15

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Divine Aleru

I am a biochemist with a deep curiosity for the human microbiome and how it shapes human health, and I enjoy making microbiome science more accessible through research and writing. With 2 years experience in microbiome research, I have curated microbiome studies, analyzed microbial signatures, and now focus on interventions as a Microbiome Signatures and Interventions Research Coordinator.

What was studied?

This study aimed to explore how host genetics, specifically IL-10 gene knockout, interacts with the gut microbiome and impacts arsenic metabolism. The researchers hypothesized that variations in the gut microbiome driven by host genetics could affect how arsenic is metabolized and whether this interaction influences arsenic toxicity. Using an integrated approach combining 16S rRNA sequencing for microbial profiling and HPLC-ICP-MS for arsenic speciation, the study examined whether the IL-10 gene knockout in mice altered the gut microbiome’s composition and, in turn, influenced arsenic biotransformation into more toxic metabolites. The study was designed to address how the microbiome influences arsenic metabolism, shedding light on individual susceptibility to arsenic-induced diseases.

Who was studied?

The study utilized C57BL/6 mice, a commonly used strain for genetic research, focusing on both wild-type and IL-10 knockout (IL-10−/−) mice. The IL-10 knockout model was selected due to IL-10’s critical role in immune regulation, which is intertwined with gut microbiome composition. The mice were exposed to arsenic in drinking water at a dose of 10 ppm for four weeks. After exposure, the researchers collected fecal samples for microbiome analysis, blood and urine for arsenic metabolite measurements, and performed histological evaluations. The aim was to see if the IL-10 gene knockout mice had significant changes in their gut microbiome compared to the wild-type mice and how these changes affected arsenic metabolism.

Most important findings

The study found that the gut microbiome composition was significantly altered in IL-10−/− mice compared to wild-type mice. The Bacteroidetes family increased, while Firmicutes decreased significantly, particularly within the Lachnospiraceae family. These changes in gut microbiome composition were linked to alterations in arsenic metabolism. Specifically, DMAsV (dimethylarsinic acid) levels were significantly reduced in the urine of IL-10 knockout mice, while MMAsV (monomethylarsonic acid) and iAsV (inorganic arsenic) levels were increased. This pattern indicates that the genetic alteration in IL-10 significantly impacted the ability of the microbiome to detoxify arsenic through methylation, leading to higher levels of more toxic arsenic species. Moreover, the ratio of MMAsV/DMAsV was higher in the knockout group, which mirrors human patterns that are associated with higher toxicity and disease risk. The study also demonstrated that the altered microbiome composition had functional impacts on arsenic metabolism, highlighting a genetic-microbiome interaction in the context of xenobiotic processing.

Key implications

This study highlights the crucial role of host genetics in shaping the gut microbiome and its capacity to metabolize arsenic. The findings suggest that individuals with specific genetic profiles, such as those with an IL-10 knockout, may be more vulnerable to arsenic toxicity due to altered microbiome-mediated biotransformation of arsenic. For clinical practice, this implies that genetic screening and microbiome profiling could be essential tools for personalizing arsenic exposure risk assessments and treatment strategies, particularly in populations exposed to contaminated drinking water. Additionally, this study contributes to the broader understanding of xenobiotic metabolism, where interactions between host genetics, gut microbiota, and environmental toxins like arsenic can influence health outcomes. For microbiome research, these findings suggest that gut microbial phenotypes, driven by genetic factors, should be considered in studies linking microbiota composition with environmental toxicants and disease susceptibility.

Arsenic (As)

Arsenic can disrupt both human health and microbial ecosystems. Its impact on the gut microbiome can lead to dysbiosis, which has been linked to increased disease susceptibility and antimicrobial resistance. Arsenic's ability to interfere with cellular processes, especially through its interaction with essential metals like phosphate and zinc, exacerbates these effects. By understanding how arsenic affects microbial communities and how these interactions contribute to disease, we can develop more effective interventions, including microbiome-targeted therapies and nutritional strategies, to mitigate its harmful effects.

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