The data comes from a randomised clinical trial, published in Nature, in which a team of researchers tested the potential effects of a special mixture included a probiotic called Lactobacillus plantarum ATCC-202195 combined with fructo-oligosaccharide (FOS), an oral synbiotic preparation developed by the team.
Led by Professor Pinaki Panigrahi from the University of Nebraska Medical Center College of Public Health, the trial involving more than 4,500 infants in India is the culmination of 15 years of research by the team – and could seriously impact infant health and save lives worldwide.
Results from the double-blind, placebo-controlled study showed that sepsis and deaths in the first two months of infancy were reduced by 40% - more than twice the anticipated reduction of 20%.
"This is the largest clinical trial of probiotics in newborns funded by the National Institutes of Health," said Panigrahi.
The effectiveness of sepsis and death prevention in infants seen was so successful the study was halted early.
Sepsis is a severe complication of bacterial infection that results in around one million infant deaths worldwide each year, mostly in developing countries.
It occurs when the immune system stops fighting germs and begins to turn on itself and can lead to tissue damage, organ failure and death.
Currently an estimated 40% of patients with severe sepsis in developing countries do not survive.
"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,” the lead researcher noted. "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," he added.
Commenting on the findings of the study, Gregor Reid, Professor of Microbiology and Immunology at Western University in Ontario, Canada, said the study is important for several reasons including the fact that the large sample size helps to further counter critics of probiotic and prebiotic research, while the challenging setting “where children die readily from sepsis shows that we can save lives anywhere if we have the will.”
Furthermore, Reid noted that while data on prevention of necrotizing enterocolitis is ‘very strong’, sepsis has remained a problem.
“This provides a very hopeful alternative to current (and often insufficient) therapy,” he told NutraIngredients. “Hopefully clinicians, including in the US and Europe where regulators prefer bureaucracy to common sense, will start to embrace probiotics and prebiotics as readily as some of the imperfect drugs they currently prescribe so avidly.”
The team enrolled 4,556 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.
During their first days of life, the newborns were randomised to receive an oral preparation containing either the specially designed symbiotic combination or a placebo for seven days.
The teams said that very few trials on the use of probiotics to prevent sepsis have focused on newborns, whose comparatively naive immune system and less complex intestinal environment would allow the probiotic to grow.
“We show a significant reduction in the primary outcome (combination of sepsis and death) in the treatment arm (risk ratio 0.60, 95% confidence interval 0.48–0.74),” wrote Panigrahi and colleagues.
Significant reductions were also reported for culture-positive and culture-negative sepsis and lower respiratory tract infections.
“These findings suggest that a large proportion of neonatal sepsis in developing countries could be effectively prevented using a synbiotic containing L. plantarum ATCC-202195,” added the team.
Also commenting on the study results, George Paraskevakos, executive director at the International Probiotic Association (IPA) noted that it is seeing more research combining probiotic and prebiotic ingredients and that current science is “starting to underline the positive impact of combining these two ingredients.”
“The research and results from this publication are very encouraging,” he said.
However the IPA's Scientific Committee noted that the potential for a synbiotic effect may not have been fully assessed because the amount of FOS used in the study was small at 150 mg – while research has suggested that safe and efficacious doses are higher.
Despite its question of whether the prebiotic dosage size was ‘meaningful’, the IPA said the results ‘remain impressive’ and “gives encouragement to both fields (Probiotic and prebiotic) working together, sharing science, and helping identify new opportunities for research in this area.”
According to Panigrahi, the formula could be a "very cheap oral sepsis vaccine” – costing just $1 per infant.
"This study has to be replicated in different countries and under different circumstances,” he said. “We maintained tight controls on the administration of the synbiotic and conducted a rigorous follow-up which will not be available in real life.”
The lead researcher also noted that it is important to find out why respiratory infections were reported to go down, and work out how the combination affects the lungs.
Professor Reid added that while the findings are very important, and show potential for preventing many infections and deaths – it is important that the industry does not attempt to use the study to market their own strains and formulations.
“I hope companies don't start saying that their 'probiotic' does the same,” commented the expert.
“Clearly, the formula was created from investigative work, and although mechanisms were not elucidated, the results do not mean other probiotics can do this,” he warned.
Published online, doi: 10.1038/nature23480
“A randomized synbiotic trial to prevent sepsis among infants in rural India”
Authors: Pinaki Panigrahi, et al