Oregon University. US: Researchers at Oregon State University have discovered that
antibiotics have an impact on the microorganisms that live in an
animal’s gut that’s more broad and complex than previously known. The findings help to better explain some of the damage these
medications can do, and set the stage for new ways to study and offset
those impacts.
The work was published online in the journal Gut, in research
supported by Oregon State University, the Medical Research Foundation of
Oregon and the National Institutes of Health.
Researchers have known for some time that antibiotics can have
unwanted side effects, especially in disrupting the natural and
beneficial microbiota of the gastrointestinal system. But the new study
helps explain in much more detail why that is happening, and also
suggests that powerful, long-term antibiotic use can have even more
far-reaching effects.
Scientists now suspect that antibiotic use, and especially overuse,
can have unwanted effects on everything from the immune system to
glucose metabolism, food absorption, obesity, stress and behavior.
The issues are rising in importance, since 40 percent of all adults
and 70 percent of all children take one or more antibiotics every year,
not to mention their use in billions of food animals. Although when used
properly antibiotics can help treat life-threatening bacterial
infections, more than 10 percent of people who receive the medications
can suffer from adverse side effects.
“Just in the past decade a whole new universe has opened up about the
far-reaching effects of antibiotic use, and now we’re exploring it,”
said Andrey Morgun, an assistant professor in the OSU College of
Pharmacy. “The study of microbiota is just exploding. Nothing we find
would surprise me at this point.”
This research used a “cocktail” of four antibiotics frequently given to laboratory animals, and studied the impacts.
“Prior to this most people thought antibiotics only depleted
microbiota and diminished several important immune functions that take
place in the gut,” Morgun said. “Actually that’s only about one-third of
the picture. They also kill intestinal epithelium. Destruction of the
intestinal epithelium is important because this is the site of nutrient
absorption, part of our immune system and it has other biological
functions that play a role in human health.”
The research also found that antibiotics and antibiotic-resistant
microbes caused significant changes in mitochondrial function, which in
turn can lead to more epithelial cell death. That antibiotics have
special impacts on the mitochondria of cells is both important and
interesting, said Morgun, who was a co-leader of this study with Dr.
Natalia Shulzhenko, a researcher in the OSU College of Veterinary
Medicine who has an M.D. from Kharkiv Medical University.
Mitochondria plays a major role in cell signaling, growth and energy
production, and for good health they need to function properly.
But the relationship of antibiotics to mitochondria may go back a
long way. In evolution, mitochondria descended from bacteria, which were
some of the earliest life forms, and different bacteria competed with
each other for survival. That an antibiotic would still selectively
attack the portion of a cell that most closely resembles bacteria may be
a throwback to that ingrained sense of competition and the very
evolution of life.
Morgun and Schulzhenko’s research group also found that one of the
genes affected by antibiotic treatment is critical to the communication
between the host and microbe.
“When the host microbe communication system gets out of balance it
can lead to a chain of seemingly unrelated problems,” Morgun said.
Digestive dysfunction is near the top of the list, with antibiotic
use linked to such issues as diarrhea and ulcerative colitis. But new
research is also finding links to obesity, food absorption, depression,
immune function, sepsis, allergies and asthma.
This research also developed a new bioinformatics approach named
“transkingdom network interrogation” to studying microbiota, which could
help further speed the study of any alterations of host microbiota
interactions and antibiotic impact. This could aid the search for new
probiotics to help offset antibiotic effects, and conceivably lead to
systems that would diagnose a person’s microbiome, identify deficiencies
and then address them in a precise and individual way.
Healthy microbiota may also be another way to address growing
problems with antibiotic resistance, Morgun said. Instead of trying to
kill the “bad” bacteria causing an illness, a healthy and functioning
microbiota may be able to outcompete the unwanted microbes and improve
immune function.
Collaborators on this research were from the OSU College of Pharmacy;
OSU College of Veterinary Medicine; OSU College of Science; the
National Cancer Institute; University of British Columbia; University of
Maryland School of Medicine; and the National Institutes of Health.