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.
Gut bacterial community
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.
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.
For more information
Jason L. Kubinak, Charisse Petersen, W. Zac Stephens,
Ray Soto, Erin Bake, Ryan M. O’Connell and June L.
Round.
MyD88 Signaling in T Cells Directs IgA-Mediated
Control of the Microbiota to Promote Health
University of Utah Health Care
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