An interdisciplinary study conducted by the University of Bern reveals that gut bacteria play a critical role in converting arsenobetaine into toxic arsenic compounds. The findings show that arsenobetaine, a compound commonly found in seafood and previously considered harmless, is partially transformed into toxic arsenic species by gut bacteria in mammals. This discovery raises new questions about the safety of seafood consumption.
Background:
Arsenic is a widespread toxic trace element found in food and water, existing in various chemical forms. Inorganic arsenic, the most common environmental form, is linked to severe health issues, including cancer, cardiovascular diseases, and neurological disorders due to long-term exposure. Consequently, the International Agency for Research on Cancer classifies inorganic arsenic as carcinogenic. Arsenobetaine, often referred to as "fish arsenic," is one of the most prevalent arsenic compounds in seafood, including algae, fish, and shellfish. It is also found in significant concentrations in certain mushrooms. Previously, arsenobetaine was considered low-risk for humans due to its low toxicity and rapid excretion.
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The primary arsenic compound found in seafood is often arsenobetaine, which has long been considered nontoxic. However, there is growing concern over whether gut microbes may convert this compound into more toxic forms.
The new study:
A new study conducted under the University of Bern's interdisciplinary research collaboration "One Health" has now demonstrated that the gut microbiome in mammals plays a key role in converting arsenobetaine into other arsenic compounds, including carcinogenic inorganic arsenic. While the role of the gut microbiome in the bioaccumulation, toxicity, and excretion of arsenic has been explored in earlier studies, prior research primarily focused on inorganic arsenic. Little was known about the microbial breakdown of arsenobetaine in the gut. New findings from an interdisciplinary team led by Prof. Dr. Siegfried Hapfelmeier of the Institute for Infectious Diseases and Prof. Dr. Adrien Mestrot of the Institute of Geography challenge previous assumptions about the safety of arsenobetaine-containing seafood. These results were recently published in the Journal of Hazardous Materials.
Successful Interfaculty Collaboration
The Bern researchers utilized gnotobiology and advanced analytical chemistry to study arsenobetaine metabolism in mice with different gut microbiome compositions. They analyzed three groups: germ-free mice (lacking gut microbes), conventional mice with natural microbiota (colonized by hundreds of microorganisms), and "gnotobiotic" mice with simplified microbiota (consisting of 12 defined bacterial species). All groups were fed an arsenobetaine-rich diet to compare arsenic metabolism, distribution in the body, and excretion.
"Access to germ-free mice from the Medical Faculty’s Clean Mouse Facility, state-of-the-art analytical equipment provided by the cLab at the Institute of Geography, and complementary expertise in gut microbiome biology and arsenic metabolism enabled this research in a truly unique way," says Dr. Teresa Chávez-Capilla, an arsenic expert and co-author of the study.
Potentially Harmful Role of Gut Microbes
The researchers found that mice with gut microbes accumulated higher concentrations of arsenic in their gastrointestinal tract than germ-free mice. "We wondered whether this was due to gut bacteria altering the chemistry of the ingested arsenic. Indeed, we observed the formation of certain highly toxic arsenic compounds in the colon of microbially colonized mice—but not in germ-free mice," explains Prof. Siegfried Hapfelmeier, a gut microbiome researcher and co-author of the study. These toxic compounds are known to accumulate more readily in the body. Accordingly, conventional mice with natural microbiota showed increased arsenic accumulation in their organs. Moreover, conventional mice switched to an arsenic-depleted purified diet excreted arsenic from their bodies much more slowly than germ-free mice. "This shows that gut microbes play a crucial role in the metabolism of arsenobetaine in the body. In this case, however, the microbiome appears to have a harmful effect," Hapfelmeier adds.
New Questions About Seafood Safety
Arsenobetaine is currently not classified as toxic and is therefore not subject to regulatory limits in food. Although previous studies suggested that arsenobetaine might be metabolized in mammals, it remained unclear whether this process was mediated by the mammalian host or its microbiome. "Translational microbiome research using mouse models has advanced significantly. While findings in mice cannot always be directly applied to humans, the very pronounced effects we observed strongly suggest that similar processes occur in humans," says Hapfelmeier.
The study highlights the importance of the microbiome for human health and aligns with the University of Bern’s focus areas on health, medicine, and sustainability. The "One Health" initiative emphasizes the interconnectedness of human, animal, and environmental health and explores how environmental factors, such as chemical toxins, affect the microbiome and overall health along the food chain. "Arsenobetaine is one of the main dietary sources of arsenic worldwide, especially in regions where seafood consumption is high," explains co-author Prof. Adrien Mestrot, an environmental chemistry expert. "The fact that arsenobetaine can be converted into more toxic forms in the mammalian gut challenges previous assumptions about food safety and has significant implications for food regulatory agencies," Mestrot concludes.
Mohana Mukherjee, Lisa Brandenburg, Yuan Dong, Stephanie Pfister, Anika Sidler, Alban Ramette, Adrien Mestrot, Teresa Chávez-Capilla, Siegfried Hapfelmeier, Microbiota-dependent in vivo biotransformation, accumulation, and excretion of arsenic from arsenobetaine-rich diet. J. Hazard. Mater., 480 (2024) 136463. DOI: 10.1016/j.jhazmat.2024.136463
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