Study examines whether giving good bacteria reduces infections

03/02/04



Dr. Robert G. Martindale, gastrointestinal surgeon and nutritionist, is giving ICU patients back good bacteria to see if it can help them avoid infections.
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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.

"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."

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