Utah University. US: As many as 1.4 million Americans suffer from
uncomfortable abdominal cramping and diarrhea that come with ulcerative
colitis and Crohn’s disease. These conditions, collectively known as
inflammatory bowel disease (IBD), are associated with an imbalance among
the thousands of species of “good” bacteria that inhabit the gut.
A
University of Utah study published on Jan. 22, 2015, in Cell Host and Microbe
demonstrates that mice deficient for a component of the immune system, a
protein called MyD88, have an imbalanced gut bacterial community – with
some species dominating over others - and are more susceptible to
contracting a severe IBD-like illness. Further, fecal transplants from
healthy donors alleviate IBD symptoms in these mice.
The results show that the immune system encourages growth of a healthy
community of “good” bacteria that is important for digestive health.
This perspective on immune system function is in contrast to it’s
best-known role as the first line of defense in the fight against
pathogens, including invasive bacteria.
“Our work highlights that the immune system shapes the composition of
bacterial communities in the intestine,” says senior author June Round, Ph.D.,
assistant professor of pathology at the University of Utah School of
Medicine. “This interaction is important because it’s becoming more and
more clear that resident microbes are very important for our health.”
Considering that some people with IBD have mutations in genes that are
part of a MyD88-controlled pathway, fecal transplantation - which
involves collecting and processing stool from a healthy donor, and
delivering it into a recipient’s gut - might help to ameliorate disease
in these people, according to Round.
Loss of MyD88 disturbs the microbial community because it disrupts
production of IgA. This class of antibody works like a gatekeeper that
controls which types of bacteria, and how many, are allowed to inhabit
the gut. By performing inventories of total gut bacteria compared to
species that bind IgA, the scientists determined that without MyD88, IgA
failed to recognize species that it can otherwise.
The work not only demonstrates that a balanced microbial community
promotes digestive health, but that it also shapes the host’s immune
system. Mice raised in a sterile, germ-free environment have a faulty
immune system, a defect that can be fixed if they are fed bacterial
components, TLR2 agonists, that activates the immune system. The rescue
does not work in mice deficient for MyD88, demonstrating again that the
protein is key to interpreting communications between microbes and the
immune system.
“There is a conversation between our immune system and our resident
bacteria,” explains Round. “The microbes can send signals that tell our
immune system how to develop and in turn our immune system can shape
what types of microbes live on our body.”
The dependency of host health on good bacteria has made the
conversation a necessity. In response to demand, the immune system has
adapted from a system designed to fight the body’s invaders to one that
also nurtures a harmonious relationship with the body’s peaceful
inhabitants.
MyD88 Signaling in T Cells Directs IgA-Mediated Control of the Microbiota to Promote Health. Jason L. Kubinak, Charisse Petersen, W. Zac Stephens, Ray Soto, Erin Bake, Ryan M. O’Connell and June L. Round. Cell Host and Microbe, Jan. 22, 2015
The work was supported by the National Institutes of Health, American
Cancer Society, Edward Mallinckrodt Jr. Foundation, Sidney Kimmel
Foundation, Pew Scholars Program, and Packard Fellowship in Science and
Engineering
The immune system promotes a healthy bacterial community in the gut
(Left) When the immune system functions properly (MyD88 is active,
green), IgA antibodies bind multiple species of bacteria, keeping the
numbers and types of “good” bacteria that inhabit the gut under control.
(Right) When the immune system is disrupted (MyD88 is inactive, gray),
IgA binds bacteria less effectively, and the bacterial community becomes
imbalanced, jeopardizing digestive health.