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Engineering a Small Intestinal Microbiome to Evaluate Food Additive Exposure

设计小肠微生物组来评估食品添加剂暴露

基本信息

批准号：
10430190
负责人：
Gretchen Mahler
金额：
$ 30.3万
依托单位：
STATE UNIVERSITY OF NY,BINGHAMTON
依托单位国家：
美国
项目类别：
财政年份：
2018
资助国家：
美国
起止时间：
2018-07-01 至 2024-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10430190
关键词：
Acute Adult Affect American Animal Model Artificial nanoparticles Bacteria Behavior Bifidobacterium bifidum Biological Biological Assay Birds Body Weight Brush Border Cecum Cell Culture Techniques Cells Characteristics Chick Chick Embryo Chicken Model Chickens Chronic Communities Consumption Data Digestion Dose Eating Engineering Enterococcus faecalis Environment Epithelial Epithelial Cells Eukaryotic Cell Exposure to Food Food Additives Food Packaging Gastrointestinal tract structure Gene Proteins Glucose Goals Health Human Human body In Vitro Individual Inflammation Ingestion Intestinal permeability Intestines Knowledge Lactobacillus casei rhamnosus Lead Lipids Liquid substance Metabolism Metal exposure Metals Methods Microbe Minerals Modeling Molecular Mucous body substance Nutritive Value Outcome Personal Satisfaction Physiological Policies Population Process Prokaryotic Cells Property Reproducibility Research Personnel Safety Scientist Small Intestines Streptococcus salivarius Structure System TNF gene Testing Tight Junctions Work Xenobiotics absorption base cell type cellular microvillus consumer product dietary dysbiosis enzyme activity gastrointestinal gastrointestinal bacteria gastrointestinal function genotoxicity gut colonization gut health gut microbiome hatching human microbiota immune function in vitro Model in vivo insight intestinal epithelium metal oxide meter microbial microbial community microbiome microbiome alteration microbiome composition microbiota microorganism nanomaterials nanoparticle nanoparticle exposure nutrient absorption oxidation prevent protein expression titanium dioxide

项目摘要

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.

项目总结

项目成果

期刊论文数量（7）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

The mechanistic effects of human digestion on magnesium oxide nanoparticles: implications for probiotics Lacticaseibacillus rhamnosus GG and Bifidobacterium bifidum VPI 1124.

DOI：
10.1039/d2en00150k
发表时间：
2022-12-01
期刊：
ENVIRONMENTAL SCIENCE-NANO
影响因子：
7.3
作者：
Garcia-Rodriguez, Alba;Stillwell, Allayah A.;Tochilovsky, Blake, V;Tanzman, Jacob, V;Limage, Rhodesherdeline;Kolba, Nikolai;Tako, Elad;Marques, Claudia N. H.;Mahler, Gretchen J.
通讯作者：
Mahler, Gretchen J.

The Role of Metal Oxide Nanoparticles, Escherichia coli, and Lactobacillus rhamnosus on Small Intestinal Enzyme Activity.