An interdisciplinary study from the University of Bern reveals that gut bacteria play a crucial role in converting arsenobetaine into toxic arsenic compounds. Results show that arsenobetaine, commonly found in seafood and previously considered harmless, is partly transformed into toxic arsenic compounds by the action of gut bacteria in the mammalian body. These findings raise new questions about the safety of seafood consumption.
Arsenic is a widespread toxic trace element found in various foods and water, existing in many chemical forms. Inorganic arsenic, the most common environmental form, is linked to serious health problems, including cancer, cardiovascular disease, and neurological disorders upon long-term exposure. As a result, the International Agency for Research on Cancer classifies inorganic arsenic as a carcinogen. Arsenobetaine is one of the most abundant arsenic compounds in marine seafood, including seaweeds, fish, and shellfish. It is consequently often referred to as ’fish arsenic’, but significant concentrations of arsenobetaine are also found in some mushrooms. Due to its low toxicity and rapid excretion, arsenobetaine has long been regarded as posing minimal risk to human health.
A new study conducted as part of the University of Bern’s Interfaculty Research Cooperation ’One Health’ now demonstrates that the mammalian gut microbiome plays a key role in the conversion of arsenobetaine into other arsenic compounds, including carcinogenic inorganic arsenic. A role of the gut microbiome in arsenic accumulation, toxicity, and excretion has been reported previously, but prior research mainly focused on inorganic arsenic. Little was known about the gut microbial degradation of arsenobetaine. New results obtained by an interdisciplinary team led by Prof. Siegfried Hapfelmeier from the Institute of Infectious Diseases and Prof. Adrien Mestrot from the Institute of Geography of the University of Bern, challenge previous assumptions about the safety of seafood containing arsenobetaine. The findings were recently published in the Journal of Hazardous Materials.
Successful Interfaculty Collaboration
The Bernese researchers used gnotobiology and advanced analytical chemistry to investigate arsenobetaine metabolism in mice with different gut microbial colonisation statuses. They studied three groups: germ-free mice (without any gut microbes), conventional mice with a natural microbiota (colonized with hundreds of microbial species), and "gnotobiotic" mice with a simplified microbiota (consisting of 12 defined intestinal bacterial species). All were fed an arsenobetaine-rich diet to compare arsenic metabolism, body distribution, and excretion. "Access to germ-free mice from the Clean Mouse Facility of the Faculty of Medicine and cutting-edge analytical instrumentation provided by the cLab of the Institute for Geography, combined with complementary expertise in gut microbiome biology and arsenic metabolism uniquely enabled this research," says Dr. Teresa Chávez-Capilla, arsenic expert and co-author of the study.
Possible harmful effects of gut microbes
The researchers discovered that mice with gut microbes accumulated higher arsenic concentrations in their intestinal tracts than germ-free mice. "We wondered if this was due to gut bacteria altering the chemistry of the arsenic ingested. Indeed, in microbially colonized mice - but not in germ-free mice - we observed the formation of specific highly toxic arsenic compounds in the large intestine", explains Prof. Siegfried Hapfelmeier, gut microbiome expert and co-author of the study. These toxic compounds are known to accumulate more readily in the body. Consistent with this, conventional mice with a natural gut microbiota showed increased arsenic accumulation in their organs. Furthermore, when switched to a low-arsenic purified diet, the clearance of arsenic from the body was significantly slower in conventional mice than in germ-free mice. "Thus, gut microbes play a crucial role in the metabolization of arsenobetaine in the body. However, in this case, the microbiome appears to have a harmful effect," Hapfelmeier adds.
New Questions About Seafood Safety
Arsenobetaine is not currently classified as toxic and is therefore not subject to legal limits in food. Although prior studies have suggested that arsenobetaine could be metabolized in mammals, it remained unclear whether this process was mediated by the mammalian host or its microbiome. "The field of translational microbiome research using mouse models has matured significantly. While mouse studies cannot be uncritically translated to humans, the striking effects we observed strongly suggest that similar processes occur in humans," says Hapfelmeier.
This work highlights the importance of the microbiome for human health and aligns with the University of Bern’s Priority Topics: Health & Medicine and Sustainability. The "One Health" collaboration considered the close interactions between human, animal and environmental health and has investigated how environmental factors like chemical toxins affect the microbiome and overall health along the food chain. "Arsenobetaine is one of the main dietary sources of arsenic worldwide, particularly in regions where seafood consumption is high", explains co-author Prof. Adrien Mestrot, and environmental chemistry expert. "The fact that arsenobetaine can be converted into more toxic forms in the mammalian gut challenges previous food safety assumptions and has significant implications for scientists and food authorities", Mestrot concludes.
