Tag Archives: Gretchen J. Mahler

Metal oxide nanoparticles and negative effects on gut health?

A May 4, 2023 Binghamton University news release by Jillian McCarthy (also on EurekAlert but published on May 9, 2023) announces the research, Note: A link has been removed,

Common food additives known as metal oxide nanoparticles may have negative effects on your gut health, according to new research from Binghamton University, State University of New York and Cornell University. 

Gretchen Mahler, professor of biomedical engineering and interim vice provost and dean of the Graduate School, worked in collaboration with Cornell researchers to study five of these nanoparticles. Their findings were recently published in the Journal of Antioxidants.

“They’re all actual food additives,” said Mahler. “Titanium dioxide tends to show up as a whitening and brightening agent. Silicon dioxide tends to be added to foods to prevent it from clumping. Iron oxide tends to be added to meats, for example, to keep that red color. And zinc oxide can be used as a preservative because it’s antimicrobial.” [emphases mine]

In order to test these nanoparticles, Mahler and Elad Tako, senior author and associate professor of food science in the College of Agriculture and Life Sciences at Cornell, used the intestinal tract of chickens. A chicken’s intestinal tract is comparable to a human’s; the microbiota that they have and the bacterial components have a lot of overlap with the microbiota that you see in the human digestive system, said Mahler. 

“We’ve been testing a series of nanomaterials here at Binghamton, and we’ve been looking at things like nutrient absorption, enzyme expression and some of the more subtle, functional markers,” said Mahler.

The doses of nanoparticles that were tested reflect what is typically consumed by humans. The nanoparticles were injected into the amniotic sac of broiler chicken eggs, which are specifically bred and raised for their meat. These chickens get larger faster, so the effects of the nanoparticles are more obvious earlier in development. The amniotic sac at a certain stage of development flows through the chicken intestine.

“When they hatched, we harvested tissue from the small intestine, the microbiota and the liver,” said Mahler. “We looked at gene expression, microbiota composition and the structure of the small intestine.”

The researchers found more negative effects with silicone dioxide and titanium dioxide. They also found that the nanoparticles had affected the functioning of the chicken’s intestinal lining (called the brush border membrane), the balance of bacteria in their intestinal tract and the chickens’ ability to absorb minerals.

The other nanoparticles had more neutral, or even positive, effects. Zinc oxide appeared to support intestinal development or compensatory mechanisms due to intestinal damage. Iron oxide could potentially be used for iron fortification, but with potential alterations in intestinal functionality and health.

Mahler doesn’t want to suggest that these nanoparticles need to be removed from our diets completely. Their research is meant to provide some information, and allow people to have a better understanding of what’s really in the food they consume.

“We’re eating these things, so it’s important to consider what some of the more subtle effects could be,” said Mahler. “We develop these gut models around this problem to try to understand it, and this collaboration, where we have these complementary methods to try to look at the problem, has been successful.”

Here’s a link to and a citation for the paper,

Food-Grade Metal Oxide Nanoparticles Exposure Alters Intestinal Microbial Populations, Brush Border Membrane Functionality and Morphology, In Vivo (Gallus gallus) by Jacquelyn Cheng, Nikolai Kolba, Alba García-Rodríguez, Cláudia N. H. Marques, Gretchen J. Mahler and Elad Tako. Antioxidants 2023, 12(2), 431, DOI: https://doi.org/10.3390/antiox12020431 Published online : 9 February 2023 (This article belongs to the Special Issue Dietary Supplements and Oxidative Stress)

This paper is open access.

Two-organ tests (body-on-a-chip) show liver damage possible from nanoparticles

This is the first time I’ve seen testing of two organs for possible adverse effects from nanoparticles. In this case, the researchers were especially interested in the liver. From an Aug. 12, 2014 news item on Azonano,

Nanoparticles in food, sunscreen and other everyday products have many benefits. But Cornell [University] biomedical scientists are finding that at certain doses, the particles might cause human organ damage.

A recently published study in Lab on a Chip by the Royal Society of Chemistry and led by senior research associate Mandy Esch shows that nanoparticles injure liver cells when they are in microfluidic devices designed to mimic organs of the human body. The injury was worse when tested in two-organ systems, as opposed to single organs – potentially raising concerns for humans and animals.

Anne Ju’s Aug. 11, 2014 article for Cornell University’s Chronicle describes the motivation for this work and the research itself in more detail,

“We are looking at the effects of what are considered to be harmless nanoparticles in humans,” Esch said. “These particles are not necessarily lethal, but … are there other consequences? We’re looking at the non-lethal consequences.”

She used 50-nanometer carboxylated polystyrene nanoparticles, found in some animal food sources and considered model inert particles. Shuler’s lab specializes in “body-on-a-chip” microfluidics, which are engineered chips with carved compartments that contain cell cultures to represent the chemistry of individual organs.

In Esch’s experiment, she made a human intestinal compartment, a liver compartment and a compartment to represent surrounding tissues in the body. She then observed the effects of fluorescently labeled nanoparticles as they traveled through the system.

Esch found that both single nanoparticles as well as small clusters crossed the gastrointestinal barrier and reached liver cells, and the liver cells released an enzyme called aspartate transaminase, known to be released during cell death or damage.

It’s unclear exactly what damage is occurring or why, but the results indicate that the nanoparticles must be undergoing changes as they cross the gastrointestinal barrier, and that these alterations may change their toxic potential, Esch said. Long-term consequences for organs in proximity could be a concern, she said.

“The motivation behind this study was twofold: one, to show that multi-organ, in vitro systems give us more information when testing for the interaction of a substance with the human body, and two … to look at nanoparticles because they have a huge potential for medicine, yet adverse effects have not been studied in detail yet,” Esch said.

Mary Macleod’s July 3, 2014 article for Chemistry World features a diagram of the two-organ system and more technical details about the research,

Schematic of the two-organ system [downloaded from http://www.rsc.org/chemistryworld/2014/07/nanoparticle-liver-gastrointestinal-tract-microfluidic-chip]

Schematic of the two-organ system [downloaded from http://www.rsc.org/chemistryworld/2014/07/nanoparticle-liver-gastrointestinal-tract-microfluidic-chip]

HepG2/C3A cells were used to represent the liver, with the intestinal cell co-culture consisting of enterocytes (Caco-2) and mucin-producing (HT29-MTX) cells. Carboxylated polystyrene nanoparticles were fluorescently labelled so their movement between the chambers could be tracked. Levels of aspartate transaminase, a cytosolic enzyme released into the culture medium upon cell death, were measured to give an indication of liver damage.

The study saw that single nanoparticles and smaller nanoparticle aggregates were able to cross the GI barrier and reach the liver cells. The increased zeta potentials of these nanoparticles suggest that crossing the barrier may raise their toxic potential. However, larger nanoparticles, which interact with cell membranes and aggregate into clusters, were stopped much more effectively by the GI tract barrier.

The gastrointestinal tract is an important barrier preventing ingested substances crossing into systemic circulation. Initial results indicate that soluble mediators released upon low-level injury to liver cells may enhance the initial injury by damaging the cells which form the GI tract. These adverse effects were not seen in conventional single-organ tests.

Here’s a link to and a citation for the paper,

Body-on-a-chip simulation with gastrointestinal tract and liver tissues suggests that ingested nanoparticles have the potential to cause liver injury by Mandy B. Esch, Gretchen J. Mahler, Tracy Stokol, and Michael L. Shuler. Lab Chip, 2014,14, 3081-3092 DOI: 10.1039/C4LC00371C First published online 27 Jun 2014

This paper is open access until Aug. 12, 2014.

While this research is deeply concerning, it should be noted the researchers are being very careful in their conclusions as per Ju’s article, “It’s unclear exactly what damage is occurring or why, but the results indicate that the nanoparticles must be undergoing changes as they cross the gastrointestinal barrier, and that these alterations may change their toxic potential … Long-term consequences for organs in proximity could be a concern … .”