Symbiosis between gut bacteria and immune system is key to health
22 July 2014
The link between gut flora and immunity to diseases is more
complex than the general view, according to research at the RIKEN
Center. The immune system itself plays a vital role in maintaining a
healthy gut flora, not just the other way round.
In recent years, studies have shown that many
diseases are triggered or maintained by changes in bacterial
communities in the gut. However, the general view up into now has
been rather simple, that the relationship is in a single direction: pathogenic bacteria
over stimulate the immune
system, leading to inflammation or autoimmune disorders.
Now, in research published in the journal Immunity ,
scientists at the RIKEN Center for Integrative Medical Science in
Japan have painted a more complex picture: the gut immune system
does not simply prevent the influx of pathogens, but is actively
involved in the maintenance of a rich and healthy community of gut
bacteria. They propose that faults in the immune regulation lead to
changes in the bacterial community that in turn feed back into the
In the study, the researchers demonstrated that the regulation by
immune T cells of immunoglobulin A (IgA), an antibody that plays a
key role in immunity in the gut, is critical for the maintenance of
rich bacterial communities in mammal guts.
They began by studying mice with various immune deficiencies and
attempted to restore their immune systems by providing the missing
components. They monitored the bacterial communities in the mice's
guts with or without the reconstitutions and evaluated the flow of
information between the immune system and bacteria. They discovered
that the precise control of IgA production by regulatory T cells is
critical for keeping a rich and balanced bacterial community.
Colonies of bacteria from mice with rich (left
poor (right panel) bacterial communities.
To investigate how bacteria feed back to the host, they looked at
germ-free mice (mice born and maintained sterile in special
incubators) and young pups that had been transplanted with different
bacterial communities (either by injection of bacteria or by
painting the fur with fecal bacteria extracts from normal or
They discovered that the immune system detects and responds
differently to different bacterial communities. Rich and balanced
bacterial communities seem to be perceived as "self" and induce a
quick maturation of the immune system and gut responses (induction
of regulatory T cells and IgA), while a poor and unbalanced
bacterial community is apparently perceived as "non-self" and
induces responses aimed at eliminating it (T cells with inflammatory
properties and IgG or IgE responses).
Diagram showing the regulatory loop between
immune system and gut bacteria.
Sidonia Fagarasan, who led the work, said, "This study should
have an impact on the way we understand immune-related disorders
associated with bacteria dysbiosis in the gut. In order to
re-establish a healthy state we need to interfere not only with the
bacteria, by providing probiotics or through faecal transplantation,
but also with the immune system, by correcting the faults caused
either by inherited deficiencies or by aging."
"It was surprising," she continues, "to see how the
reconstitution of T cell-deficient mice with a special regulatory T
cell type leads to dramatic changes in gut bacterial communities. It
was spectacular to see how the immune system perceives and reacts to
different bacteria communities. It gives us hopes that with a better
knowledge of the symbiotic relationships between the immune system
and bacteria in the gut, we could intervene and induce modifications
aiming to re-establish balance and restore health."
1. Shimpei Kawamoto, Mikako Maruya, Lucia M. Kato, Wataru
Suda, Koji Atarashi, Yasuko Doi, Yumi Tsutsui, Hongyan Qin, Kenya
Honda, Takaharu Okada, Masahira Hattori, and Sidonia Fagarasan,
Foxp3+ T Cells Regulate Immunoglobulin A Selection and Facilitate
Diversification of Bacterial Species Responsible for Immune
Homeostasis. Immunity, doi: 10.1016/j.immuni.2014.05.016