Gut Bacteria Play Key Role in Immune System
By Michael Smith, North American Correspondent, MedPage Today
Published: October 16, 2008
Reviewed by Dori F. Zaleznik, MD; Associate Clinical Professor of
Medicine, Harvard Medical School, Boston.

NEW YORK, Oct. 16 -- The development of key immune cells is triggered
by specific types of bacteria in the gut, a finding that could lead to
new therapies for diseases of inflammation, researchers here said.

In the absence of bacteria from the cytophaga-flavobacter-
bacteroidetes phylum -- or CFB, for short -- the immune cells are also
not present, at least in mice, according to Dan Littman, M.D., Ph.D.,
of New York University, and colleagues.

On the other hand, when bacteria from that phylum are introduced into
animals lacking them, the result is a restoration of Th17 immune
cells, Dr. Littman and colleagues said in the Oct. 16 issue of Cell
Host & Microbe.Action Points
--------------------------------------------------------------------------------

Explain to interested patients that commensal intestinal bacteria play
important roles in maintaining health by aiding in digestion and
helping to ward off pathogens, among other things.


Note that this study suggests that specific types of commensal
bacteria also play a role in stimulating production of cells of the
immune system, which may open the door to new ways to treat
inflammatory diseases.
Th17 cells -- CD4-positive cells that have a potent pro-inflammatory
effect-- are normally in a balance with another population of CD4-
positive cells, dubbed Foxp3-positive cells, which play a regulatory
role in the immune system.


The finding that different populations of gut bacteria influence the
development of the Th17 cells could open the door to new treatments
for inflammatory bowel disease and other illnesses of the immune
system, Dr. Littman said.


"The number of inflammatory diseases known to involve T helper 17
cells seems to be growing every week," Dr. Littman said. For that
reason, he and colleagues have been studying the development of the
cells.


In a series of experiments in mice, he and colleagues showed that a
complete absence of so-called commensal bacteria in the small
intestine leads to a lack of Th17 cells. Commensal bacteria are the
useful organisms that help in digestion and aid in protecting against
pathogens.


In commercially available germ-free mice -- which have a complete lack
of bacteria and fungi -- Th17 cells were not detectable and the
presence of interleukin-17 secreted by the cells was at the limit of
detectability.


On the other hand, Foxp3-positive cells were increased, even though
the total number of CD4-positive cells was two- to three-fold lower
than normal.


When the researchers used a cocktail of antibiotics to destroy the
commensal bacteria, they found that the proportion of Th17 cells fell
by half after four weeks of treatment. In mice given the cocktail from
birth, the proportion of Th17 cells was 80% lower than in control
animals by six to eight weeks of age.


Dr. Littman and colleagues then broke out individual antibiotics to
see if they influenced the number of Th17 cells. Vancomycin (Vancocin)
-- which mainly attacks Gram-positive bacteria -- had a similar effect
to the whole cocktail.


On the other hand, antibiotics that attack anaerobic and Gram-negative
bacteria had little effect.


More than 90% of the commensal intestinal bacteria -- in both mice and
humans -- are either members of the Gram-negative CFB phylum or the
Gram-positive Firmicutes phylum, the researchers noted.


A series of experiments showed that members of the CFB phylum are not
present in animals that lack Th17 cells, Dr. Littman and colleagues
said, although those from the Firmicutes phylum remain.


The researchers found that some strains of experimental mice have
intestinal bacteria but no Th17 cells. Comparing those animals with
other strains, Dr. Littman and colleagues discovered that CFB bacteria
were associated with the creation of Th17 cells.


Exactly which members of the CFB phylum induce the cells is currently
under study, the researchers said.


"It's not the amount of microbial flora but the kind of microbial
flora that seems to count," Dr. Littman said.


The findings point to ways of manipulating the immune system,
commented Yasmine Belkaid, Ph.D., of the National Institutes of
Health, one of the sponsors of the study.


"There is more and more evidence that gut flora have a tremendously
important influence on human health," Dr. Belkaid said in a statement.
"This new study is the first report that has associated a defined set
of gut flora with the induction of specific immune cells."


The study was supported by the Howard Hughes Medical Institute, the
Helen and Martin Kimmel Center for Biology and Medicine, the Sandler
Program for Asthma Research, the National Gnotobiotic Rodent Resource
Center, the NIH, the Phillip Morris Foundation, and the Canadian
Institutes of Health Research. The researchers did not report any
conflicts.





Additional source: Cell Host & Microbe
Source reference:
Ivanov II, et al "Specific Microbiota Direct the Differentiation of
IL-17-Producing T-Helper Cells in the Mucosa of the Small
Intestine"Cell Host & Microbe 2008; 4: 337-349.

http://www.medpagetoday.com/InfectiousDisease/GeneralInfectiousDisease/11343