Research
Beneficial Bacteria
Part 3
Study Examines Whether Giving Good Bacteria Reduces Infections

Dr.
Robert G. Martindale, gastroinestinal surgeon and nutritionist,
is giving ICU
patients back good bacteria to see if it can help them avoid
infections.
3-3-2004
Whether giving good bacteria that normally helps keep the
intestinal tract and immune system healthy can reduce infections
in intensive-care patients is the focus of a new clinical
study at the Medical College of Georgia.
"When
people are admitted to intensive care on broad-spectrum
antibiotics, we know that 25 to 40 percent of them will
get an infection with a resistant bacteria during their
stay," says Dr. Robert G. Martindale, gastrointestinal
surgeon, nutritionist and principal investigator on the
new study.
As
the name indicates, these antibiotics are designed to protect
patients from infection by a broad range of agents. However,
they also can wipe out the natural bacterial flora in the
intestinal tract, a disruption with widespread consequences
including making the intestinal lining more susceptible
to bacterial invasion, impacting the health of colon cells
and disarming the immune system.
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"We kill all the normal bacteria in our GI tracts,
allow these abnormal bacteria to grow and we are in trouble, we have
upset the balance," says Dr. Martindale who restores the balance
in patients who arrive at MCG Medical Center critically ill from sepsis
following routine surgery.
He first prescribes more targeted antibiotic therapy,
then returns some of the primary healthy bacteria, such as lactobacillus
plantarum, that play many important roles including maintaining a
healthy intestinal lining, protecting from invaders such as Salmonella
and E. coli, encouraging the activity of macrophages, an immune system
component that gobbles up invaders and preventing diarrhea.
"We know very well that the source of sepsis
in these patients, 50 to 70 percent of the time, is their own intestines,"
Dr. Martindale says. "The question is, 'Why?' Why do bacteria
from our own intestines that normally live with us in a nice, healthy
relationship become aggressive and infective? Because we give these
broad-spectrum antibiotics, we have big operations, GI bleeds …
all these things destroy the normal lining of the intestines. Now
these bacteria become aggressive."
Giving good bacteria, called probiotics, is accepted
therapy in many countries. But even though the bacteria can be found
on grocery-store shelves, the therapy has not caught on in the germ-vigilant
U.S.A., Dr. Martindale says.
"Americans don't like the concept," he says,
and because the bacteria already are available and affordable, there
is little financial incentive for pharmaceutical companies to get
involved, although a company not involved in making probiotics is
sponsoring his new study.
He hopes the study, the country's first large, randomized
trial to assess probiotics' effectiveness in reducing infections in
ICU patients, will help change that.
Eligible patients include those on broad-spectrum
antibiotics admitted to adult ICUs at MCG Medical Center. Louisiana
State University in Shreveport also will enroll patients and the University
of Maryland in Baltimore likely will as well, Dr. Martindale says.
He plans to enroll a total of 400 patients in one
of three study arms he designed. Twice a day for 10 days, patients
will receive either a placebo, probiotics or probiotics in conjunction
with non-digestible fibers called prebiotics, which encourage the
growth and activity of good bacteria. Pairing prebiotics and probiotics
is called symbiotics.
"These bacteria are good," says Dr. Martindale
and it's not just hospitalization and antibiotics that are destroying
them. Rather, it's the American lifestyle in general, with its emphasis
on cleanliness and a diet low in fiber and high in refined, processed
food that is weakening the natural, protective mechanisms of the gut
and surrounding immune cells. "Humans that eat a good mixed diet
with lots of fiber have plenty of Lactobacillus plantarum. Americans
have little," he says.
Dr. Martindale has spent two years exploring probiotics'
potential in restoring a healthy, normal flora including collaborating
with Dr. Vadivel Ganapathy, biochemist and interim chair of the MCG
Department of Biochemistry and Molecular Biology, who studies nutrient
transport systems.
In research currently published as an accelerated
communication in the Journal of Biological Chemistry, Dr. Ganapathy
helps explains the importance of eating fruits and vegetables and
not abusing antibiotics. His work details SLC5A8, a transporter that
he has found delivers short-chain fatty acids to colonic cells to
help keep them healthy. This was a missing piece of the puzzle of
how the colonic cells use glucose found in the indigestible plant
cells walls that make it to the colon. Good bacteria produce an enzyme
that enables the glucose to be released. In the process of fermenting
this glucose so it can be used as energy, bacteria also produce energy-packed
short-chain fatty acids.
Dr. Ganapathy found that the transporter, SLC5A8,
delivers these fatty acids to colon cells. When colon cells don't
get enough of this preferred nutrient, they can become sick and cancerous.
Drs. Martindale and Ganapathy are pursing the idea that the transporter
also delivers short-chain fatty acids to nearby immune cells to keep
them healthy as well. The gastrointestinal tract, which runs a path
through the middle of the body, has more immune cells than any other
part of the body, Dr. Martindale says. Those immune cells must stay
vigilant so they can assess everything that moves through the tract.
"Clearly, the National Institutes of Health,
the National Cancer Institute, all of the national organizations will
say to lower your risk of cancer, you need to eat mixed fruits and
vegetables," Dr. Martindale says. "And, if we eat more fruits
and vegetables, it fits right along with this, you get more fiber,
you get more fermentation substrates to the bacteria that live in
your colon. If you start looking at the data on what bacteria do for
us, there truly is a mutualistic relationship between us and the bacteria
that live in our colon."
This story has been adapted from a news release issued
by Medical College Of Georgia, www.mcg.edu.
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