A large clinical trial in India finds a synbiotic may help prevent neonatal sepsis

Sepsis is a life-threatening condition characterized by systemic inflammation; it is one of the major contributors to neonatal mortality, especially in developing countries. The World Health Organization (WHO) estimates that 1 million deaths per year (10% of all under-five mortality) are due to neonatal sepsis and that 42% of these deaths occur in the first week of life. Although exclusive breastfeeding and chlorhexidine antisepsis interventions (on vaginal areas, newborn skin and the umbilical cord) have been proven to benefit neonatal health in low-resource settings, no prophylactic tool is widely used.

A new community-based, double-blind, placebo-controlled randomized trial, led by Dr. Ira H. Gewolb from the Division of Neonatology at College of Human Medicine at Michigan State University (East Lansing, Michigan, USA), has found that a synbiotic consisting of a strain of Lactobacillus plantarum and fructooligosaccharide may be effective in preventing sepsis in rural Indian newborns. Synbiotics are combinations of a probiotic -the Lactobacillus plantarum strain – with a prebiotic – here the fructooligosaccharide.

The researchers enrolled 4,556 healthy newborns -all of them weighing at least 2,000 g at birth, born at 35 weeks of gestation or later, who were breastfed and had no signs of sepsis or other morbidity- from 149 randomly chosen rural Indian villages and monitored them for 60 days. It is noteworthy that neonatal and infant mortality rates in the studied region are among the highest in India, according to the Department of Health & Family Welfare from the Government of Odisha state.

Infants in the treatment arm (n = 2,278) took a daily dose of the synbiotic (consisting of a capsule containing 109 colony forming units of Lactobacillus plantarum ATCC strain 202195 and 150 mg of fructooligosaccharide with 100 mg maltodextrin as excipient) for one week, whereas the placebo group (n = 2,278) took capsules containing only 250 mg of maltodextrin.

Primary outcome was a composite of sepsis (composed of septicaemia, meningitis, culture-negative sepsis, and low respiratory tract infections) or death. Secondary outcomes were other infections (including diarrhoea, omphalitis, local infections, abscess, and otitis media) and weight gain.

The colonizing ability, tolerance and impact on the stool microbiota of administration of L. plantarum ATCC strain 202195 in combination with fructooligosaccharide was previously reported in newborns by the same research group. The probiotic strain was initially isolated from healthy volunteers’ stool and when administered to infants colonized their gut successfully and remained there for up to 4 months.

Newborn babies who took the synbiotic had a significantly lower risk of developing sepsis. Just 5.4% of the infants who took the synbiotic developed sepsis in their first 2 months of life, compared to 9% of those who received a placebo. The researchers calculated that the reduction of sepsis risk was between 25-50%. Some sepsis cases in newborn babies begin in the gut and the symbiotic may prevent them by either ousting pathogenic microorganisms or stopping commensal ones from entering the bloodstream and causing infections.

Apart from preventing sepsis, the synbiotic also reduced the risk of infection by Gram-positive bacteria (by 82%), Gram-negative bacteria (by 75%), and pneumonia and other airway-related infections (by 34%).

Regarding tolerance and safety, the symbiotic was well tolerated and did not cause any harmful side effects. Only 6 cases of abdominal distention were reported across both groups.

To sum up, this is the first large clinical trial that has found benefits of a symbiotic for sepsis prevention in newborns from a developing country. “We may need to test this in different settings and we are working with the government to do so,” says the first author Dr. Panigrahi. In an article in The Atlantic, Ed Yong writes, “Beyond protecting infants… this approach would also reduce the use of antibiotics, and slow the spread of drug-resistant infections. And perhaps best of all, it can be done cheaply. You would need to treat 27 infants to prevent one case of sepsis, and each week-long course costs just one U.S. dollar.”



Panigrahi P, Parida S, Nanda NC, et al. A randomized synbiotic trial to prevent sepsis among infants in rural India. Nature. 2017. doi: 10.1038/nature23480.

Paul Enck
Paul Enck
Prof. Dr. Paul Enck, Director of Research, Dept. of Psychosomatic Medicine and Psychotherapy, University Hospital Tübingen, Germany. His main interests are gut functions in health and disease, including functional and inflammatory bowel disorders, the role of the gut microbiota, regulation of eating and food intake and its disorders, of nausea, vomiting and motion sickness, and the psychophysiology and neurobiology of the placebo response, with specific emphasis on age and gender contributions. He has published more than 170 original data paper in scientific, peer-reviewed journals, and more than 250 book chapters and review articles. He is board member/treasurer of the European Society of Neurogastroenterology and Motility and of the German Society of Neurogastroenterology and Motility, and has served as reviewer for many international journals and grant agencies.