HUMAN-MICROBIOME INTERACTIONS TO TOLERATE A POTENT TOXICANT

Inorganic arsenic is a potent toxicant and millions of people worldwide ingest arsenic in food and water.

We recently identified genetic variants associated with efficient arsenic metabolism in populations in the Andes Mountains; this is the first documented case of natural selection in humans for defence against a toxic chemical. However, genetic variation cannot completely explain arsenic metabolism.

Recent studies in mice show that the microbiome confers arsenic tolerance, but the human genome–microbiome interplay in arsenic tolerance is largely unknown. This project will elucidate the role of the microbiome and its interaction with human genetics for arsenic toxicity.

We will 1) determine whether populations with elevated, prolonged arsenic exposure have adapted by changes in genetics and the microbiome, and how these adaptations influence arsenic metabolism and health effects. 2) Identify and characterise the bacteria that confer arsenic tolerance.

We will study a cohort of women in the Bolivian Andes, from groups who have lived in arsenic-rich environments for generations.

We will characterise their arsenic exposure and metabolism using mass spectrometry, their microbiome by 16S rDNA sequencing, arsenic-related health effects by immune markers, transcriptome and genotoxicity, and human genetics by genome-wide association.

Understanding how the microbiome protects against arsenic could produce probiotic therapies that mitigate the effects of this toxic metal.