October 31, 2023 - Gretchen Mahler, Ph.D.
From Erin Atkins
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Gretchen Mahler, Ph.D.
Professor, Biomedical Engineering Department, Binghamton University
Development of a Small Intestinal Model for Assessing the Impact of Food Additives
Abstract
A Western diet includes engineered nanoparticles (NP) on the order of μg per day, primarily as metal oxide NP used in processed foods and food packaging. The effects of NP on small intestinal function are not well understood. The goal of our work is to determine if and how ingested metal oxide NP alter gut microbiota populations and intestinal function. The human small intestine is the primary site of macronutrient digestion and absorption, but it is also difficult to access, making sampling and experimentation a challenge. We have developed static and organ-on-a-chip cell culture models of the proximal gastrointestinal (GI) tract that include digestion, a mucus layer, physiologically relevant human cell types including immune cells, and a reproducible, stable, human bacteria-derived synthetic small intestinal microbiome. Data generated with these in vitro models and validated with an in vivo Gallus gallus (broiler chicken) model shows that dietary doses of metal oxide NP alter brush border membrane (BBM) enzyme function, decrease mineral, glucose, and lipid absorption, alter bacterial populations and mucus composition, and can induce monocyte differentiation toward macrophages. Decreases in nutrient absorption are due to NP-induced alterations in microvilli structure, mucus content, and bacterial population changes. Beneficial bacterial strains ameliorate negative NP effects, but NP adsorption onto bacteria can result in decreased bacterial viability. These advancements to an in vitro model of the small intestine can provide a novel method for understanding the human response to environmental contaminants and food additives.
Speaker Biography
Gretchen Mahler is a Professor in the Biomedical Engineering Department in the Watson College of Engineering at Binghamton University, part of the State University of New York (SUNY) system. She also serves as the Interim Vice Provost and Dean of the Graduate School. Gretchen earned her BS in Chemical Engineering from the University of Massachusetts Amherst in 2002. She completed her honors thesis with Dr. Susan Roberts. Dr. Mahler completed her Ph.D. in Chemical and Biomolecular Engineering with Dr. Michael Shuler at Cornell University in 2008. In 2011, Gretchen completed a postdoctoral fellowship at Cornell University in the Biomedical Engineering Department with Dr. Jonathan Butcher. Dr. Mahler joined the Biomedical Engineering Department at Binghamton University in 2011. Her research interests include the development, characterization, and validation of cell culture organ and tissue microfluidic models. Her current research includes the development of barrier tissue organs on a chip, including the GI tract, liver, kidney, and vascular and valvular endothelium, for mechanobiological and toxicity testing.
Abstract
A Western diet includes engineered nanoparticles (NP) on the order of μg per day, primarily as metal oxide NP used in processed foods and food packaging. The effects of NP on small intestinal function are not well understood. The goal of our work is to determine if and how ingested metal oxide NP alter gut microbiota populations and intestinal function. The human small intestine is the primary site of macronutrient digestion and absorption, but it is also difficult to access, making sampling and experimentation a challenge. We have developed static and organ-on-a-chip cell culture models of the proximal gastrointestinal (GI) tract that include digestion, a mucus layer, physiologically relevant human cell types including immune cells, and a reproducible, stable, human bacteria-derived synthetic small intestinal microbiome. Data generated with these in vitro models and validated with an in vivo Gallus gallus (broiler chicken) model shows that dietary doses of metal oxide NP alter brush border membrane (BBM) enzyme function, decrease mineral, glucose, and lipid absorption, alter bacterial populations and mucus composition, and can induce monocyte differentiation toward macrophages. Decreases in nutrient absorption are due to NP-induced alterations in microvilli structure, mucus content, and bacterial population changes. Beneficial bacterial strains ameliorate negative NP effects, but NP adsorption onto bacteria can result in decreased bacterial viability. These advancements to an in vitro model of the small intestine can provide a novel method for understanding the human response to environmental contaminants and food additives.
Speaker Biography
Gretchen Mahler is a Professor in the Biomedical Engineering Department in the Watson College of Engineering at Binghamton University, part of the State University of New York (SUNY) system. She also serves as the Interim Vice Provost and Dean of the Graduate School. Gretchen earned her BS in Chemical Engineering from the University of Massachusetts Amherst in 2002. She completed her honors thesis with Dr. Susan Roberts. Dr. Mahler completed her Ph.D. in Chemical and Biomolecular Engineering with Dr. Michael Shuler at Cornell University in 2008. In 2011, Gretchen completed a postdoctoral fellowship at Cornell University in the Biomedical Engineering Department with Dr. Jonathan Butcher. Dr. Mahler joined the Biomedical Engineering Department at Binghamton University in 2011. Her research interests include the development, characterization, and validation of cell culture organ and tissue microfluidic models. Her current research includes the development of barrier tissue organs on a chip, including the GI tract, liver, kidney, and vascular and valvular endothelium, for mechanobiological and toxicity testing.
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