The external tissues of plants and animals are colonized by microbial communities termed microbiota. When organisms are exposed to environmental pollutants, these substances will therefore... Show moreThe external tissues of plants and animals are colonized by microbial communities termed microbiota. When organisms are exposed to environmental pollutants, these substances will therefore encounter microbiota at the exposure interface. Many antimicrobial substances have been found to disturb beneficial interactions between microbiota and the host, thereby impairing host health. Nanomaterials exhibit nanoscale properties that could affect host health in two additional, understudied, microbiota-dependent ways. Firstly, owing to their large surface area, adsorption interactions between nanomaterials, microbial metabolites and microbes could alter the identity and colloidal stability of nanomaterials, and may influence the dispersal of microbes. Secondly, the immuno-modulatory effects of microbiota could affect the sensitivity of hosts to immunotoxic nanomaterials. In this dissertation, we use a combination of computational techniques and zebrafish larvae experiments to unravel and quantify these interactions. We predict the affinity of microbial metabolites to carbon and metal nanomaterials, and show that titanium dioxide nanoparticles can affect the dispersal of microbes through aquatic ecosystems, and across different life stages of oviparous animals. Additionally, we provide insight into microbiota-dependent signaling pathways that affect the sensitivity of zebrafish larvae to particle-specific, immunotoxic effects of silver nanoparticles. Altogether, these results contribute to mechanistic pathways for microbiota-inclusive nanomaterial safety assessment. Show less
Ingested nanomaterials are exposed to many metabolites that are produced, modified, or regulated by members of the enteric microbiota. The adsorption of these metabolites potentially affects the... Show moreIngested nanomaterials are exposed to many metabolites that are produced, modified, or regulated by members of the enteric microbiota. The adsorption of these metabolites potentially affects the identity, fate, and biodistribution of nanomaterials passing the gastrointestinal tract. Here, we explore these interactions using in silico methods, focusing on a concise overview of 170 unique enteric microbial metabolites which we compiled from the literature. First, we construct quantitative structure–activity relationship (QSAR) models to predict their adsorption affinity to 13 metal nanomaterials, 5 carbon nanotubes, and 1 fullerene. The models could be applied to predict log k values for 60 metabolites and were particularly applicable to ‘phenolic, benzoyl and phenyl derivatives’, ‘tryptophan precursors and metabolites’, ‘short-chain fatty acids’, and ‘choline metabolites’. The correlations of these predictions to biological surface adsorption index descriptors indicated that hydrophobicity-driven interactions contribute most to the overall adsorption affinity, while hydrogen-bond interactions and polarity/polarizability-driven interactions differentiate the affinity to metal and carbon nanomaterials. Next, we use molecular dynamics (MD) simulations to obtain direct molecular information for a selection of vitamins that could not be assessed quantitatively using QSAR models. This showed how large and flexible metabolites can gain stability on the nanomaterial surface via conformational changes. Additionally, unconstrained MD simulations provided excellent support for the main interaction types identified by QSAR analysis. Combined, these results enable assessing the adsorption affinity for many enteric microbial metabolites quantitatively and support the qualitative assessment of an even larger set of complex and biologically relevant microbial metabolites to carbon and metal nanomaterials. Show less
