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Principal Investigator: Gretchen Mahler
Organization: STATE UNIVERSITY OF NY,BINGHAMTON
Fiscal Year: 2022
Award: $302,964
Funding agency: National Institute of Environmental Health Sciences
PROJECT SUMMARY
Nanomaterials are increasingly used in consumer products, processed food, and food packaging, and few
studies have determined the consequences of nanoparticle ingestion. The ultimate goal of this work is to
determine if and how ingested metal oxide nanoparticles alter microorganism populations and intestinal function.
A model of the GI tract and a panel of functional assays have been developed, and preliminary data shows that
dietary doses of pristine metal oxide nanoparticles decrease mineral, glucose, and lipid absorption. These
decreases in absorption are due to nanoparticle-induced alterations in microvilli structure. The presence of a
single species of beneficial bacteria in the model prevents changes in nutrient absorption following nanoparticle
exposure, and early results suggest that nanoparticle reactivity with biological components is related to metal
oxidation state. The central hypothesis is that the microbiota can detoxify ingested metal oxide nanomaterials,
but high doses or chronic exposure can induce small intestinal dysbiosis, alter intestinal epithelial structure, and
result in decreased barrier properties and nutrient absorption. This hypothesis will be tested with three aims.
First, individual strains of bacteria will be introduced into the GI tract model and molecular, functional, and
structural epithelial characteristics and microbial viability and genotoxicity affected by acute and chronic metal
oxide nanoparticle exposure will be identified. Second, a mock community of upper GI bacteria will be engineered
and incorporated into the GI tract model to determine the effects of acute or chronic metal oxide nanoparticle
exposure on microbial community dynamics and epithelial cell properties under both static and fluidic conditions.
Third, a broiler chicken model (Gallus gallus), which is an established and robust method for quantifying nutrient
bioavailability, brush border enzyme activity, and microbiome alterations will be used to validate in vitro results.
This system, which will be the first to model upper GI conditions using a physiologically realistic, reproducible,
high-throughput method with human-derived cells, will provide insight into nanoparticle-biological interactions.
This valuable information is necessary for health and safety decisions and will be provided to both researchers
and consumers. The scientific outcomes of this work are twofold: 1) the model created will allow quantitative
assessment of the contributions of bacteria toward GI health and function and the ability to determine how what
we eat governs microbial dynamics; and 2) data collected will determine the overarching behavior of metal oxide
nanoparticles with biological GI components and allow for extrapolation across a broad class of commonly
ingested nanomaterials.
Terms: <(TNF)-α><21+ years old><Actinobacterium bifidum><Actinomyces bifidus><Actinomyces parabifidus><Acute><Adult><Adult Human><Affect><Alimentary Canal><American><Animal Model><Animal Models and Related Studies><Artificial nano particles><Artificial nanoparticles><Assay><Aves><Avian><B bifidum><B. bifidum><Bacillus bifidus><Bacillus bifidus communis><Bacteria><Bacterium bifidum><Bacteroides bifidus><Behavior><Bifidibacterium bifidum><Bifidobacterium bifidum><Bioassay><Biologic Assays><Biologic Nutritional Availability><Biological><Biological Assay><Birds><Body Weight><Brush Border><Cachectin><Cecum><Cell Body><Cell Culture Techniques><Cells><Cellular Immune Function><Characteristics><Chick><Chick Embryo><Chicken Model><Chicken animal model><Chickens><Chronic><Cohnistreptothrix bifidus><Communities><Consumption><D-Glucose><Data><Dextrose><Digestion><Digestive Tract><Dose><E faecalis><E. faecalis><Eating><Engineering><Enterococcus faecalis><Environment><Epithelial><Epithelial Cells><Eukaryotic Cell><Exposure to><Food><Food Additives><Food Intake><Food Packaging><Food or Food Product><GI Tract><GI colonization><GI microbiome><Gallus domesticus><Gallus gallus><Gallus gallus domesticus><Gastrointestinal Tract><Gastrointestinal tract structure><Gene Proteins><Glucose><Goals><Gut Epithelial Permeability><Gut Hyperpermeability><Gut permeability><Health><Human><Human Figure><Human body><In Vitro><Individual><Inflammation><Ingestion><Intermediary Metabolism><Intestinal><Intestinal Epithelial Permeability><Intestinal Hyperpermeability><Intestinal permeability><Intestines><Investigators><Knowledge><L rhamnosus><L. rhamnosus><Lactobacillus bifidus type II><Lactobacillus casei rhamnosus><Lactobacillus parabifidus><Lactobacillus rhamnosus><Lead><Lipids><Liquid substance><Macrophage-Derived TNF><Metabolic Processes><Metabolism><Metal exposure><Metals><Methods><Microbe><Microvilli><Microvillus><Minerals><Modeling><Modern Man><Molecular><Monocyte-Derived TNF><Mucous body substance><Mucus><Nocardia bifida><Nutritional Availability><Nutritional Biological Availability><Nutritive Value><Occluding Junctions><Outcome><Pb element><Personal Satisfaction><Physiologic><Physiological><Policies><Population><Process><Prokaryotae><Prokaryotic Cells><Property><Protein Gene Products><Reproducibility><Research Personnel><Researchers><S faecalis><S salivarius><S. faecalis><S. salivarius><Safety><Scientist><Small Intestines><Streptococcus Group D><Streptococcus faecalis><Streptococcus salivarius><Striated Border><Structure><System><TNF><TNF A><TNF Alpha><TNF gene><TNF-α><TNFA><TNFα><Testing><TiO2><Tight Junctions><Tissieria bifida><Tumor Necrosis Factor><Tumor Necrosis Factor-alpha><Work><Xenobiotics><Zonula Occludens><absorption><adulthood><alimentary tract><alter microbiome><base><biologic><bowel><cell culture><cell cultures><cell type><cellular microvillus><chicken embryo><community microbes><consumer product><dietary><digestive canal><digestive tract microbiome><dysbacteriosis><dysbiosis><dysbiotic><engineered nano particle><engineered nanoparticle><enteric microbiome><enzyme activity><exposure to metal><fluid><gastrointestinal><gastrointestinal bacteria><gastrointestinal function><gastrointestinal microbiome><gastrointestinal tract colonization><genotoxicity><gut colonization><gut health><gut microbiome><gut-associated microbiome><hatching><heavy metal Pb><heavy metal lead><human flora><human microbial communities><human microbiota><human microflora><human-associated microbial communities><human-associated microbiota><immune function><in vitro Model><in vivo><insight><intestinal biome><intestinal colonization><intestinal epithelium><intestinal microbiome><liquid><metal oxide><meter><microbial><microbial community><microbial consortia><microbial flora><microbial imbalance><microbiome><microbiome adaptation><microbiome alteration><microbiome community composition><microbiome composition><microbiome perturbation><microbiome species composition><microbiota><microflora><microorganism><model of animal><model organism><mucous><multispecies consortia><nano materials><nano particle><nano-sized particle><nanomaterials><nanoparticle><nanoparticle exposure><nanosized particle><nutrient absorption><nutrient bioavailability><oxidation><prevent><preventing><prokaryote><protein expression><small bowel><titanium dioxide><titanium oxide><well-being><wellbeing>