At Last, a Big, Successful Trial of Probiotics (2017)
A large Indian study of 4,500 newborn babies found that the right microbes can prevent a life-threatening condition called sepsis.
For all the hype that surrounds them, probioticsproducts that contain supposedly beneficial bacteriahave rarely proven their worth in large, rigorous studies. There are good reasons for this disappointing performance. The strains in most commercially produced probiotics were chosen for historical reasons, because they were easy to grow and manufacture, and not because they are well-adapted to the human body. When they enter our gut, they fail to colonize. As I wrote in my recent book, theyre like a breeze that blows between two open windows.
But even though probiotic products might be underwhelming, the probiotic concept is sound. Bacteria can beneficially tune our immune systems and protect us from disease. Its just a matter of finding the right strains, and helping them to establish themselves. Many scientists are now trying to do just that, and one such team, led by Pinaki Panigrahi at the University of Nebraska Medical Center, has just scored a big win.
Since 2008, Panigrahis team has been running a large clinical trial in rural India, where they gave a probiotic of their own devising to thousands of randomly selected newborn babies. Their product contained a strain of Lactobacillus plantarum, chosen for its ability to attach to gut cells. The team also added a sugar, chosen to nourish the microbe and give it a foothold when it enters
a babys gut. Together, this combination is called a synbiotic. And it was strikingly effective.
The team found that babies who took this concoction had a significantly lower risk of developing sepsisa life-threatening condition where infections trigger body-wide inflammation, restricted blood flow, and organ failure. Sepsis is one of the biggest killers of newborn babies, ending around 600,000 lives every year when theyve barely begun. Some proportion of these cases begin in the gut, and probiotics might be able to prevent them by ousting harmful microbes, or by stopping benign ones from crossing into the bloodstream and causing infections.
Sure enough, in Panigrahis trial, just 5.4 percent of the infants who took the synbiotic developed sepsis in their first two months of life, compared to 9 percent of those who received a placebo. Thats a reduction of 40 percent. Such estimates always come with a margin of error, but the team calculate that the reduction in risk should still be somewhere between 25 and 50 percent.
Its not surprising that a one-size-fits-all approach hasnt worked thus far.
The effect was twice as large as what the team expected, especially since the infants took daily doses of the synbiotic for just one week. And given the clear evidence of benefits, independent experts who were monitoring the study decided to stop the trial early: It would have been unethical to continue depriving half the newborns of the treatment. Panigrahi originally planned to enroll 8,000 babies into the study. He stopped at 4,557.
Which is still a huge number! Probiotics trials have been criticized in the past for being small and statistically underpowered. Those that looked at sepsis, for example, usually involved just 100 to 200 babies, making it hard to know whether any beneficial effects were the result of random chance. The biggest trial to date included 1,315 infants; Panigrahis study is over three times bigger. [It] exemplifies how intervention research should be done, writes Daniel Tancredi from the University of California, Davis, in a commentary that accompanies the paper.
In most studies, people take the probiotics that are available on the shelf without asking why that probiotic should work in the disease theyre interested in. And they think theyll stumble onto something good, says Panigrahi. Its counter-intuitive, but we did the same thing.
At first, his team tested Lactobacillus GG and Lactobacillus sporogenesthe most commonly used probiotics in Indiain small pilot studies. Both strains are claimed to colonize the gut. We did the trial and the colonization was almost zero, says Panigrahi. To f
