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other·preclinical research, biomedical research, gastroenterology, endocrinology, nutrition·PMC10540274

Interactions between arsenic exposure, high-fat diet and NRF2 shape the complex responses in the murine gut microbiome and hepatic metabolism

Frontiers in Microbiomes · 7 authors, 4 centres

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TL;DR

This study used wild-type and Nrf2 knockout mice to show that chronic inorganic arsenic exposure and a high-fat diet interact with NRF2 to alter the gut microbiome and hepatic metabolism. The findings demonstrate that dietary differences caused strong, overlapping changes in microbial and metabolic profiles.

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Dietary differences were a major driver, causing strong overlap in responses between the microbiome and metabolome datasets.

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other

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preclinical research

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ORIGINAL PAPER

PMC10540274

Interactions between arsenic exposure, high-fat diet and NRF2 shape the complex responses in the murine gut microbiome and hepatic metabolism

Frontiers in Microbiomes

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ABSTRACT

Inorganic arsenic (iAs) exposure has been associated to various detrimental effects such as development of metabolic syndrome and type 2 diabetes via oxidative stress and induced prolonged activation of the NRF2 transcription factor. Such effects can be aggravated by poor dietary habits. The role of gut microbiota in promoting metabolic changes in response to arsenic has yet to be precisely defined. To address the complexity of the interactions between diet, NFE2L2 /NRF2, and gut microbiota, we studied the chronic effects of iAs exposure in wild-type (WT) and Nrf2 -/- mice fed normal (ND) vs. high-fat diet (HFD), on the gut microbial community in the context of hepatic metabolism. We demonstrate that all treatments and interactions influenced bacteria and metabolic profiles, with dietary differences causing a strong overlap of responses between the datasets. By identifying five metabolites of known microbial origin and following their fate across treatments, we provide examples on how gut microbial products can participate in the development of iAs and HFD-induced metabolic disease. Overall, our results underline the importance of the microbial community in driving gut-liver-cross talk during iAs and HFD exposure.

CITATION EXPORT

Gabriele Schiro, Pengfei Liu, Matthew Dodson et al.. Interactions between arsenic exposure, high-fat diet and NRF2 shape the complex responses in the murine gut microbiome and hepatic metabolism. Frontiers in Microbiomes. (2022). https://doi.org/10.3389/frmbi.2022.1041188

AUTHORS

7 · 4 CENTRES

Gabriele Schiro, Pengfei Liu, Matthew Dodson, Donna D. Zhang, Fayez K. Ghishan, Albert Barberán, Pawel R. Kiela

1 Department of Environmental Science, University of Arizona, Tucson, AZ, United States
2 Department of Pediatrics, University of Arizona, Tucson, AZ, United States
3 Department of Pharmacology and Toxicology, College of Pharmacy, University of Arizona, Tucson, AZ, United States
4 National and Local Joint Engineering Research Center of Biodiagnosis and Biotherapy, and International Joint Research Center on Cell Stress and Disease Diagnosis and Therapy, The Second Affiliated Hospital of Xi’an Jiaotong University, Xi’an, China