Research
Helpful Bacteria
Part 2
Teamwork In The Intestine: Gut Bacteria Interact With
Intestine To Regulate Blood Supply
11-4-2002
St. Louis, Bacteria aren't always bad. In fact, they can
be extremely helpful partners. According to research at
Washington University School of Medicine in St. Louis, microbes
found naturally in the mouse and human gut interact with
intestinal cells, called Paneth cells, to promote the development
of blood vessels in the intestinal lining.
"This
study provides insights into the mutually beneficial partnerships
forged between mammals and their native microbes,"
says principal investigator Jeffrey I. Gordon, M.D., the
Dr. Robert J. Glaser Distinguished University Professor
and head of the Department of Molecular Biology and Pharmacology.
"These symbiotic relationships probably are most important
in the gut, which contains the largest and most complex
collection of bacteria."
Gordon's
team found that a key developmental program – orchestrating
formation of blood vessels in the gut following birth –
is a responsibility shared by intestinal bacteria and their
host. The study appears in the November 5 issue of the Proceedings
of the National Academy of Sciences; Thaddeus S. Stappenbeck,
M.D., Ph.D., instructor of molecular biology and pharmacology,
is first author and Lora Hooper, Ph.D., instructor of molecular
biology and pharmacology, is co-author.
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The team examined three groups of six-week-old male
mice. One group of animals was reared with normal bacteria; another
group was reared without any intestinal bacteria; a third group began
bacteria-free but then were colonized with microbes taken from intestines
of normal mice.
An imaging technique called confocal microscopy provided
three-dimensional images of sections of intestinal tissue taken from
each group of animals. The images offer a clear view of cells and
blood vessels in tissue samples, and allow investigators to measure
the density of capillaries, small blood vessels in the wall of the
intestine.
In mice lacking intestinal bacteria, blood vessel
formation stopped early during postnatal development. Remarkably,
this developmental program restarted and was completed just 10 days
after implanting microbes into bacteria-free mice.
Moreover, colonization by one particular type of bacteria
commonly found in normal mouse and human intestine, called Bacteroides
thetaiotaomicron, or B. thetaiotaomicron, stimulated blood vessel
development as efficiently as implantation of a whole microbial society.
The researchers also examined the pathway by which
bacteria influence blood vessel formation. They engineered mice lacking
Paneth cells, normal components of the intestinal lining that help
defend the body against attacks by harmful bacteria. Without Paneth
cells, blood vessels could not completely develop, even when microbes
such as B. thetaiotaomicron were introduced. The team concluded that
B. thetaiotaomicron and Paneth cells work together to stimulate postnatal
blood vessel formation.
"Our findings illustrate the importance of co-evolution
of animals and their microbial partners," says Gordon. "Bacteria
that live in the intestine appear to provide mammals with several
necessary services for healthy development. Unraveling the molecular
foundations of these relationships may provide new ways of preventing
or treating a variety of diseases."
Reference: Stappenbeck TS, Hooper LV, Gordon JI. Developmental
regulation of intestinal angiogenesis by indigenous microbes via Paneth
cells. Proceedings of the National Academy of Sciences, November 5,
2002.
Funding from the National Institutes of Health, AstraZeneca
and the Burroughs-Wellcome Foundation supported this research.
The full-time and volunteer faculty of Washington
University School of Medicine are the physicians and surgeons of Barnes-Jewish
and St. Louis Children's hospitals. The School of Medicine is one
of the leading medical research, teaching and patient-care institutions
in the nation. Through its affiliations with Barnes-Jewish and St.
Louis Children's hospitals, the School of Medicine is linked to BJC
HealthCare.
This story has been adapted from a news release issued
by Washington University School Of Medicine, medinfo.wustl.edu.
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