Human-based methodologies to study toxicity of food nanoparticles on fatty liver diseases via the microbiota-bile acid axis.

ongoing

Daily ingestion of nanoparticles (NPs) is inevitable due to their wide use by the food sector, some as bactericidal agents. But their antimicrobial effects towards our gut bacteria remain largely unknown. While some studies investigated their impact on microbial composition, very few explored microbial functional changes and significance for host health. It is alarming that our gut microbiome, unanimously recognized as central in many diseases, is currently overlooked in nanotoxicology. Among key roles of microbiota, we and others underlined that secondary bile acids (BA), generated by the gut bacteria, regulate inflammation in the liver by interacting with host receptors. We showed in mice that altered BA pool in the portal blood, connecting the gut to the liver, exacerbated chronic fatty liver disease, an increasingly prevalent disorder representing a major unmet medical need. Assembling the two puzzle pieces, I was the first to explore the impact of some food NPs on fatty liver diseases via the microbiota-BA axis in mice. But BA metabolism differs between species stressing the need to rely on human data. The current knowledge gaps on microbial BA metabolism, the inaccessibility of the portal blood and the challenges in testing NPs ex vivo hamper such study in fatty liver disease patients. Drawing on promising preliminary data and using human-based methodologies, I aim to timely elucidate if microbial BA dysmetabolism and resulting altered portal BA pool drives fatty liver diseases and if ingestion of food NPs contribute to fatty liver diseases via this microbiota-BA axis. I anticipate that the new approach methodologies and mechanistic knowledge derived from this proposal will offer the scientific community a toolbox towards ‘precision toxicology’ to assess potential toxicity of food NPs (and other food chemicals) on microbiota-BA-liver axis in humans, supporting the necessary implementation of preventive actions at both the individual and population level.