Gut Bacteria Play Key Role In Immune System

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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.

 

 

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

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