A randomized synbiotic trial to prevent sepsis among infants in rural India

Abstract

Sepsis in early infancy results in one million annual deaths worldwide, most of them in developing countries. No efficient means of prevention is currently available. Here we report on a randomized, double-blind, placebo-controlled trial of an oral synbiotic preparation (Lactobacillus plantarum plus fructooligosaccharide) in rural Indian newborns. We enrolled 4,556 infants that were at least 2,000 g at birth, at least 35 weeks of gestation, and with no signs of sepsis or other morbidity, and monitored them for 60 days. 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), with few deaths (4 placebo, 6 synbiotic). Significant reductions were also observed 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.

Skin microbiota–host interactions

“…A clearer understanding of the dense network of microbe–microbe interactions will also allow us to provide more targeted therapies for dysbiosis, which has been implicated in atopic dermatitis but is also being explored as a pathogenic contributor to many other skin diseases, including psoriasis, hidradenitis suppurativa, and lupus erythematosus. In the gut, using microbes to correct dysbiosis has been successful in the case of faecal transplants for Clostridium difficile infections 142 , and more recently in the use of a Lactobacillus plantarum synbiotic to prevent neonatal sepsis 143 . Similar live microbial therapies for the skin have not yet been developed.…”

Designing synbiotics for improved human health

“…The design of a synbiotic, then, requires only that the probiotic exerts a greater effect in the presence of a prebiotic than in its absence, and vice versa. Unfortunately, few experiments address this consideration: prebiotics are not routinely combined with a corresponding probiotic to show an increased benefit to the host than in the absence of either component, as was the case in a recent synbiotic trial to prevent sepsis among infants in rural India (Panigrahi et al ., 2017). Future experimental work on the effects of synbiotics should assess not only the effect of the prebiotic on the probiotic, but the change in effect on the host in combination versus in isolation.…”

Gut microbes as future therapeutics in treating inflammatory and infectious diseases: Lessons from recent findings

“…This intervention strategy found effective in preventing the toxicity of irinotecan (an anticancer drug) in mice [302]. Recently, perturbation of gutmicrobial communities through the synbiotic approach by providing Lactobacillus plantarum (probiotic) in combination with the fructo-oligosaccharide (prebiotic) reduced the number of newborn deaths caused by sepsis [303]. The mechanism of protection involves restoration of gut epithelial barrier function through upregulating mucus production and inducing host immunity leading to the secretion of antimicrobial peptide and inhibiting pathogen translocation [304].…”