For all the air time they’re given, you’d expect probiotics to do wonders but the truth is rigorous studies to back up these claims have been few and far between. The concept seems sound, the theory is there, but practical results just haven’t been that convincing. Well, in the culmination of two decades’ work, Pinaki Panigrahi of the University of Nebraska Medical Center might have just convincingly proven that probiotics work at least in one area: they fight infant sepsis.

Understanding probiotics

It’s one of the few large-scale rigorous probiotic trials that reported great success. Image credits: Brian Gratwicke.

Probiotics are basically live microorganisms that allegedly provide health benefits when consumed. There are numerous commercial claims about the benefits of probiotics, including reducing gastrointestinal discomfort, improving immune health, relieving constipation, or avoiding the common cold. However, these claimed benefits have not been thoroughly proven (though they haven’t been disproven either).

Another problem, writes Ed Yong for The Atlantic, is that commercial strains of probiotics were chosen because they were easy to grow and manufacture, and not based on their performance in the human body. Most times, they completely fail to colonize the human body, becoming, as Yong puts it, a “breeze that blows between two open windows.” But again, since the concept seems sound, researchers haven’t given up on probiotics.

In a massive study, Dr. Panigrahi used them to tackle one of the biggest causes for infant mortality: sepsis.

“This is the largest clinical trial of probiotics in newborns funded by the National Institutes of Health,” Dr. Panigrahi said. The team enrolled more than 4,500 newborns from 149 villages in the Indian province of Odisha and followed them for their first 60 days, the most critical period when they get sick and die.

Fighting sepsis

The probiotic cocktail could save hundreds of thousands of infants in India alone. Image credits: Etan Sivad.

Sepsis arises when the body’s response to infection causes injury to its own tissues and organs. It’s estimated that sepsis kills around one million infants each year, mostly in developing countries. But it’s not just developing countries that are battling the problem. In the US, the inpatient cost for hospitals treating sepsis is nearly $24 billion each year.

Since 2008, Panigrahi and colleagues have been carrying a randomized, double-blind, placebo-controlled study. They traveled 149 villages in rural India, giving infants a concoction containing a strain of Lactobacillus plantarum, chosen for its ability to attach to gut cells. The probiotic cocktail also contained sugar, which was meant to provide nutrients for the microorganisms and help them get a foothold inside the infants’ bodies. “It’s food for the bugs,” Panigrahi says.

The results were so successful that the study was stopped early — when results are so conclusive, studies are often stopped because it is considered unethical to keep adding people to the placebo group.

“We were concerned when the data safety and monitoring board stopped the study prematurely. We had enrolled just about half of our proposed subjects. Typically, a study is stopped when something is wrong.”

“But, it was a moment of superlative thrill when we learned it was stopped due to early efficacy. We were surprised a second time when the complete data analysis showed that respiratory tract infections also were reduced — something we did not anticipate in our population,” Dr. Panigrahi said.

Infants who were given the probiotic cocktail were 40% less likely to develop sepsis. Just 5.4 percent of the infants developed sepsis, compared to the 9% who were given a placebo. The probiotic formula could be a “very cheap oral sepsis vaccine,” Dr. Panigrahi said.

The benefits extend far beyond just saving lives. Infants who get sepsis can suffer from lingering damage their entire life, such as stunted growth and impaired cognitive function.

There are two directions for continuing the study. First, researchers want to try the same thing in different parts of the world, to see if there are cultural or environmental factors which affect the rate of success. Secondly, they want to understand the exact mechanism through which the cocktail fended off sepsis.

“This study has to be replicated in different countries and under different circumstances. We maintained tight controls on the administration of the synbiotic and conducted a rigorous follow-up which will not be available in real life,” he said.

“We have to find out why respiratory infections went down. How does this treatment affect the lungs?”

Journal Reference: Pinaki Panigrahi et al — A randomized synbiotic trial to prevent sepsis among infants in rural India. doi:10.1038/nature23480