Oregon: Researchers at Oregon State University and other institutions have discovered an important link between the immune system, gut bacteria and glucose metabolism – a “cross-talk” and interaction that can lead to type 2 diabetes and metabolic syndrome when not functioning correctly.
The findings, published today in Nature Communications, are one
example of how different mammalian systems can affect each other in ways
not previously understood. A better understanding of these systems, researchers say, may lead to new probiotic approaches to diabetes and other diseases.
The research also shows the general importance of proper bacterial
functions in the gut and the role of one bacteria in particular –
Akkermansia muciniphila - in helping to regulate glucose metabolism.
This bacteria’s function is so important, scientists say, that it has
been conserved through millions of years of evolution to perform a
similar function in both mice and humans.
“We’re discovering that in biology there are multiple connections and
communications, what we call cross-talk, that are very important in
ways we’re just beginning to understand,” said Dr. Natalia Shulzhenko,
an assistant professor in the OSU College of Veterinary Medicine, and
one of the corresponding authors on this study.
“It’s being made clear by a number of studies that our immune system,
in particular, is closely linked to other metabolic functions in ways
we never realized. This is still unconventional thinking, and it’s being
described as a new field called immunometabolism. Through the process
of evolution, mammals, including humans, have developed functional
systems that communicate with each other, and microbes are an essential
part of that process.”
It had been previously observed that an immune mediator - one type of
interferon, or signaling protein called IFN-y – can affect the proper
function of glucose metabolism. IFN-y helps fight several pathogens and
infections, but a decrease in its levels can lead to improvement in
glucose metabolism. However, this actual process has not been
“Before this, no one had a clue exactly how IFN-y affected glucose
tolerance,” said Andrey Morgun, an assistant professor in the OSU
College of Pharmacy and also a corresponding author on the study. “The
involvement of microbes had not really been considered. But with the
help of a statistical model and an approach we call a transkingdom
network, we were able to pinpoint some likely bacterial candidates.”
The bacteria A. muciniphila, was found to play a critical role in
this communication process – in their study, the scientists called it a
“missing link.” Research showed that mice specially bred with reduced
levels of IFN-y had higher levels of A. muciniphila, and significantly
improved glucose tolerance. When IFN-y levels increased, A. muciniphila
levels declined, and glucose tolerance was reduced.
Similar observations were also made in humans. It’s been observed,
for instance, that athletes who are extremely fit have high levels of
the gut bacteria A. muciniphila, which is a mucus-degrading bacteria.
The research makes clear that two systems once believed to be
functionally separate – immunity and glucose metabolism – are, in fact,
closely linked, and the bridge can be provided by gut bacteria.
There’s probably more than one bacteria involved in this process of
communication and metabolic control, researchers said. The gut harbors
literally thousands of microbes that appear to function almost as a
metabolically active organ, emphasizing the critical importance of gut
Bacteria-mediated communication, of course, is just one part of
complex human systems – issues such as proper diet, exercise, and
appropriate weight control are all still important, the researchers
This research was supported by the National Institutes of Health.
Other collaborating researchers were from the University of Sao Paulo in
Brazil, University of North Carolina, National Institute of Allergy and
Infectious Diseases, and Duke University Medical Center. Co-first
authors were Renee Greer of the OSU College of Veterinary Medicine and
Xiaoxi Dong of the OSU College of Pharmacy.