by University of
California - San Diego
Touted by
makers as a "healthy" alternative to traditional nicotine cigarettes,
new research indicates the chemicals found in e-cigarettes disrupt the gut
barrier and trigger inflammation
in the body, potentially leading to a variety of health concerns.
In the
study, published Jan. 5, 2021 in the journal iScience, Soumita Das, Ph.D.,
associate professor of pathology, and Pradipta Ghosh, MD, professor of cellular
and molecular medicine at UC San Diego School of Medicine and Moores Cancer Center at UC San Diego
School of Medicine, with colleagues, found that chronic use of nicotine-free
e-cigarettes led to a "leaky gut," in which microbes and other
molecules seep out of the intestines, resulting in chronic inflammation. Such
inflammation can contribute to a variety of diseases and conditions, including
inflammatory bowel disease, dementia, certain cancers, atherosclerosis, liver
fibrosis, diabetes and arthritis.
"The
gut lining is an amazing entity. It is comprised of a single layer of cells
that are meant to seal the body from the trillions of microbes, defend our
immune system, and at the same time allow absorption of essential
nutrients," said Ghosh. "Anything we eat or drink, our lifestyle
choices in other words, has the ability to impact our gut microbes, the gut
barrier and overall health. Now we know that what we smoke, such as
e-cigarettes, negatively impacts it as well."
The
researchers found that two chemicals used as a base for all e-cigarette liquid
vapor—propylene glycol and vegetable glycerol—were the cause of inflammation.
"Numerous
chemicals are created when these two are heated to generate the fumes in vaping
that cause the most damage, for which there are no current regulations,"
said Ghosh. "The safety of e-cigarettes have been debated fiercely on both
sides. Nicotine content, and its addictive nature, has always been the major
focus of those who argue against its safety, whereas lack of chemicals in the
carcinogens that are present in the cigarette smoke has been touted by the
makers of e-cigarettes when marketing these products as a 'healthy
alternative.' In reality, it's the chemicals making up the vapor liquid that we
should be more concerned about as they are the cause of gut inflammation."
For the
study, the team used 3-D models of human intestinal tracts generated from
patient cells and simulated what happens when e-cigarette vapors enter the gut
lining. Researchers validated the findings using mice models of vaping in
collaboration with Laura Crotty-Alexander, MD, associate professor of medicine
in the Division of Pulmonary, Critical Care and Sleep Medicine at UC San Diego
School of Medicine and section chief of Pulmonary Critical Care at Veterans
Affairs San Diego Healthcare System.
To produce
the 3-D gut organoids, the researchers collected stem cells from patients'
biopsies during colonoscopies and grew them in vitro. The stem cells
differentiated into the four different cell types that make up the gut lining.
The team then exposed the organoids to e-cigarette liquid vapor, mimicking the
frequency of a chronic vaper.
They noted
that epithelial tight conjunction markers, which are zipper-like proteins that
form the gut's first physical barrier, began to break or loosen, causing
pathogens from the vapor to seep into the surrounding immune system, wreaking
havoc on protective epithelial cells that lie just beneath.
Such cells
act as a defense against infection by clearing pathogenic microbes and
initiating certain immune responses in the body. When exposed to the
e-cigarette liquid, the cells were quickly overwhelmed, unable to effectively
clear pathogens, resulting in gut inflammation.
The study is
part of the HUMANOID Center of Research Excellence,
a core facility based at UC San Diego School of Medicine led by Ghosh and Das
who was senior author of the study. Scientists at the center use a variety of
human organoids and other tools to model diseases and effects.
"This
is the first study that demonstrates how chronic exposure to e-cigarettes
increases the gut's susceptibility to bacterial infections,
leading to chronic inflammation and other health concerns," said Das.
"Given the importance of the gut barrier in the maintenance of the body's
immune homeostasis, the findings provide valuable insight into the potential
long-term harmful effects chronic use of e-cigarettes on our health."
Ghosh
said damage to the gut lining may be reversible over time if the inciting
factor, in this case e-cigarette use, is eliminated, but the effects of chronic
inflammation upon other organs, such as the heart or brain, may be
irreversible. In the future, Ghosh said she and colleagues plan to look at
different flavorings of e-cigarettes to determine what effects they might have
on the gut.
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