Benign—Not: Unexpected deaths in probiotics study

Prescribing “good” bugs for the gut—it may sometimes be bad medicine.

That’s what Dutch doctors have concluded after reviewing the findings of a novel treatment in people with acute pancreatitis.

The researchers knew that some of their 296 patients would succumb to infectious complications of an inflamed pancreas, a gland that makes hormones and digestive juices. But they never expected that patients provided nutrition laced with probiotics—supposedly beneficial gut microbes—would experience a death rate nearly triple that of people fed just the nutrients.

Yogurts and other foods or dietary supplements containing probiotics have reduced infections and the severity of gastrointestinal disorders in many trials. So, Dutch physicians looked to see if probiotics would similarly benefit newly diagnosed acute-pancreatitis patients.

All the patients received food pumped directly into the small intestine. For half the recruits, the food was laced with a novel mix of six strains of bacteria. During the trial, neither the patients nor the doctors running the experiments knew who had received the twice-daily supplements of bacteria, each for a 1-month period.

Although the overall death rate in the trial matched the value typically seen with acute pancreatitis—11 percent—just 6 percent of the untreated patients died. In contrast, 16 percent of patients receiving the probiotics died. This “was shocking,” says study leader Marc G.H. Besselink of University Medical Center in Utrecht, the Netherlands. “We’re quite devastated.”

His group reports its findings in a paper in the Feb. 23 Lancet.

Nearly one-third of each group developed infections, but the probiotic bacteria did not cause them in the treated group. “We know,” Besselink explains, “because we did blood cultures” to identify the agents responsible. Tests also ruled out any tainting of the probiotics with infectious germs.

What the team did find were nine cases of bowel ischemia—eight of them fatal—a condition in which tissue dies from oxygen starvation, allowing germs and toxins to escape into the body. In each case, the patient had received probiotics.

Besselink surmises that the oxygen demand of microbes introduced into an already stressed digestive system might have contributed to the suffocation of bowel cells. Or, he says, gut cells might simply have viewed the probiotic bacteria as a threat and inappropriately revved up an immune reaction against them, producing collateral damage to the bowel.

As the Dutch researchers begin animal tests of these hypotheses, they advise other physicians to avoid use of probiotics for patients with acute pancreatitis and for people in intensive care units, or where probiotics will be delivered through a tube directly into the intestines.

The study showed a striking survival benefit for administering food into the small intestine, already a type of therapy, notes gastroenterologist David C. Whitcomb of the University of Pittsburgh. The error, he suspects, was seeding probiotics into the same place, a region normally all but devoid of microbes.

The stomach and colon are rife with microbial life, he notes, and trials that deposited probiotics in these regions have shown promise. By contrast, he points out, earlier studies that sterilized the intestine with antibiotics—the antithesis of probiotics—improved the prognosis of acute pancreatitis sufferers.

Lee E. Morrow of Creighton University Medical Center in Omaha, Neb., sees no need to generalize the Dutch trial’s findings to all critically ill patients. His team has been administering a single Lactobacillus GG probiotic to roughly 200 intensive care patients with head trauma and other conditions that require breath support from a ventilator. Doses are delivered partly by mouth and partly by tube into the stomach.

This ongoing trial is showing “clear, statistically significant benefits in reducing ventilator-associated pneumonia,” Morrow says. “So [the Dutch findings] are certainly not stopping our study.”