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https://medicalxpress.com/news/2018-12-gut-microbiome-intestinal-immune.html?fbclid=IwAR0v71IUUoJvggWnrkJIpzvks7jZ7ync8vpLoXcLltVd10lbayHkSdB91WY


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Gut microbiome regulates the intestinal immune system, researchers
find December
18, 2018 by Mollie Rappe  , Brown University <http://www.brown.edu/>
[image: Gut microbiome regulates the intestinal immune system, researchers
find]
<https://3c1703fe8d.site.internapcdn.net/newman/gfx/news/hires/2018/2-gutmicrobiom.jpg>
Brown researchers found that the amount of vitamin A-converting protein,
shown in green, varied between the guts of normal mice (CV) and mice
without gut bacteria (GF). Credit: Vaishnava Lab/Immunity

Scientist have long known that bacteria in the intestines, also known as
the microbiome, perform a variety of useful functions for their hosts, such
as breaking down dietary fiber in the digestive process and making vitamins
K and B7.

Yet a new study unveils another useful role the microbiome plays. A team of
researchers from Brown University found that in mice, the gut microbiome
regulates the host's immune system—so that rather than the host's defense
system attacking these helpful bacteria
<https://medicalxpress.com/tags/helpful+bacteria/>, the bacteria can
co-exist peacefully with the immune system.

What's the trick to the microbiome's work with the immune system? Vitamin
A—the bacteria moderate active vitamin
<https://medicalxpress.com/tags/vitamin/> A levels in the intestine,
protecting the microbiome from an overactive immune response.

That insight may prove important for understanding and treating autoimmune
and inflammatory diseases
<https://medicalxpress.com/tags/inflammatory+diseases/>, said Shipra
Vaishnava, an assistant professor of molecular microbiology and immunology
at Brown.

"A lot of these diseases are attributed to increased immune response or
immune activation, but we've found a new way that bacteria in our gut can
dampen the immune response," Vaishnava said. "This research could be
critical in determining therapies in the case of autoimmune diseases such
as Crohn's disease or other inflammatory bowel diseases, as well as vitamin
A deficiency."

The study was published on Tuesday, Dec. 18, in the journal *Immunity*.

*Microbiomes of mice and men*

The gut microbiome is an ecosystem made of 100 trillion bacteria that have
evolved to live in the special conditions of the intestines, Vaishnava
said. The vast majority of these bacteria do not harm their hosts but are
helpful instead. A healthy microbiome, just like a healthy forest, has many
species co-existing together and can fend off hostile intruders—such as
disease-causing bacteria or invasive species.

In both humans and mice, the phyla Firmicutes and Bacteroidetes comprise
the majority of the gut microbial community. To play their part in
regulating their hosts' immune systems, the bacteria in the microbiome
fine-tune the levels of a protein responsible for the conversion of vitamin
A to its active form in their hosts' gastrointestinal tract, the
researchers found.

Vaishnava's team found that Firmicutes bacteria, particularly members of
the class Clostridia, reduce the expression of a protein within the cells
that line the intestines. The protein, retinol dehydrogenase 7 (Rdh7)
converts dietary vitamin A to its active form, retinoic acid, Vaishnava
said. The Clostridia bacteria, common to both mice and men, also promote
increased vitamin A storage in the liver, the team found.

Vaishnava expects the findings are generalizable to the interactions
between the human microbiome and their hosts as well.

Mice genetically engineered to not have Rdh7 in their intestinal cells have
less retinoic acid in the intestinal tissue, as the researchers expected.
Specifically, the guts of the engineered mice had fewer immune cells that
make IL-22, an important cellular signal that coordinates the antimicrobial
response against gut bacteria. Other components of the immune system such
as cells with immunoglobulin A and two types of T-cells were the same as in
standard mice, suggesting Rdh7 is only essential for the regulating
antimicrobial response, Vaishnava said.

The researchers do not know exactly how Rdh7 is suppressed, but Clostridia
bacteria are known to produce short chain fatty acids that change host gene
expression. As a next step in their research, the team will study how
bacteria regulate Rdh7 expression, including examining various short chain
fatty acids, Vaishnava said.

In addition, the team will conduct research to understand why Rdh7
suppression is critical. They are working to genetically engineer mice to
always express Rdh7 in their intestinal cells. Vaishnava wants to see how
this affects the mouse microbiome and if it leads to any inflammation or
autoimmune disease-like conditions for the mice. They will also explore the
impacts of increased vitamin A storage in the liver due to bacteria Rdh7
regulation, Vaishnava said.

*Helping human health*

The researchers say that understanding how bacteria regulate the immune
system's responses could be important in unlocking the keys to disorders
like Crohn's disease.

Data from clinical studies has shown that inflammation in the bowel is a
result of disrupted interactions between a host and their gut microbiome
<https://medicalxpress.com/tags/gut+microbiome/>, Vaishnava said.

"The role of vitamin A in inflammation is context-dependent and is very
hard to tease apart," Vaishnava said. "A change in vitamin A status and
vitamin A metabolic genes coincides with inflammatory bowel diseases, but
we don't know if this promotes inflammation or not. We hope that adding our
finding—that bacteria can regulate how vitamin A is being metabolized in
the intestine or stored—could help clarify why the field is seeing what it
is seeing."

These findings could also provide clues about the importance of the
microbiome <https://medicalxpress.com/tags/microbiome/> in addressing
vitamin A deficiency, a problem that is particularly prevalent in Africa
and Southeast Asia.

Vitamin A deficiency affects approximately one third of children under the
age of five, according to the World Health Organization (WHO). Vitamin A
deficiency weakens the immune system
<https://medicalxpress.com/tags/immune+system/> and increases the risk of
infectious diseases. The WHO has been providing at-risk children with
vitamin A supplements for the past 25 years, but it hasn't been as
successful as hoped for, according to Vaishnava. This study shows bacteria
are a big part of vitamin A absorption and storage and perhaps children
need to have the right combination of bacteria in the gut in order for the
vitamin A supplements to be most effective, she added.

"Both our diet and the bacteria in our gut are critically linked in
regulating how our immune cells behave," Vaishnava said. "Finding what
those links are at a molecular level is important to figuring out how we
could use either diet or bacteria <https://medicalxpress.com/tags/bacteria/>,
or both of them together, to have a therapeutic effect in inflammatory or
infectious diseases."

<https://medicalxpress.com/news/2018-12-gut-microbiome-intestinal-immune.html?fbclid=IwAR0v71IUUoJvggWnrkJIpzvks7jZ7ync8vpLoXcLltVd10lbayHkSdB91WY#>
*Explore
further:* Scientists uncover protective influence of Vitamin A against
inflammatory bowel disease
<https://medicalxpress.com/news/2013-06-scientists-uncover-vitamin-inflammatory-bowel.html>

*More information:* Mayara Grizotte-Lake et al, Commensals Suppress
Intestinal Epithelial Cell Retinoic Acid Synthesis to Regulate
Interleukin-22 Activity and Prevent Microbial Dysbiosis, *Immunity*
(2018). DOI:
10.1016/j.immuni.2018.11.018
<http://dx.doi.org/10.1016/j.immuni.2018.11.018>

*Journal reference:* Immunity
<https://medicalxpress.com/journals/immunity/> [image:
search and more info] <https://medicalxpress.com/journals/immunity/> [image:
website] <http://www.cell.com/immunity/home>

*Provided by:* Brown University
<https://medicalxpress.com/partners/brown-university/> [image: search and
more info] <https://medicalxpress.com/partners/brown-university/> [image:
website] <http://www.brown.edu/>