The probiotic Escherichia coli strain Nissle 1917 (EcN) stops acute diarrhoea in infants and toddlers Original paper

What was studied?

The Escherichia coli Nissle 1917 acute diarrhoea treatment was tested in a multicentre, randomized, double-blind, placebo-controlled Phase III trial in infants and toddlers to determine whether an oral EcN suspension could shorten the duration of acute infectious diarrhoea compared with placebo and to confirm its safety in very young children. The trial defined response very clearly as a fall in stool frequency to three or fewer loose stools in 24 hours for at least two consecutive days. The probiotic was administered once to three times daily, depending on age, with each millilitre containing 10⁸ viable EcN. Follow-up lasted up to 10 days or until a response was observed. The study also documented stool pathogens, abdominal pain, vomiting, temperature, and tolerance, allowing for the separation of clinical benefit from the usual rapid spontaneous recovery seen in pediatric gastroenteritis. The background was that EcN has microcin production, barrier support, and immune modulation, so the authors wanted to see if these mechanisms translate into faster clinical resolution in routine viral or unspecific diarrhoea.

Who was studied?

A total of 113 Caucasian children aged 2 to 47 months were enrolled across 11 paediatric centres in Russia and Ukraine during one winter–spring season when viral gastroenteritis is common, and they all had more than three watery or loose stools per day for no longer than three days at baseline. Fifty-five children received EcN suspension, and fifty-eight received a placebo suspension that appeared identical, with doses adjusted according to age: 1 ml once daily in infants under one year, twice daily in toddlers aged 1 to 3 years, and three times daily in toddlers over 3 years but under 4 years. Children with dehydration above 5%, with antibiotics or other live products, or with chronic bowel disease were excluded to keep the cohort homogeneous and to avoid confounders. Pathogen screens showed mostly viral or nonspecific causes, with a minority of bacterial detections, which matches everyday paediatric practice. Parents kept daily stool and symptom diaries, and investigators confirmed findings at visits.

Most important findings

EcN led to a significantly faster clinical response than the placebo, with a median time to response of 2.5 days for EcN and 4.8 days for the placebo. This difference of 2.3 days was statistically significant at p = 0.0007. Ninety-four point five percent of EcN children met the response definition within 10 days, compared with 67.2% on placebo, indicating that almost all EcN recipients stopped experiencing acute diarrhoea within the observation window. The separation of response curves began on day 3 and continued to widen through day 5, indicating a biological rather than chance effect. Stool consistency normalised more often in the EcN arm and abdominal pain and cramps resolved in more EcN recipients. Pathogen clearance was similar in both arms, so EcN did not act by eradicating the organism but by supporting host control. No safety signals appeared, with adverse events reported in only 3.6% of EcN versus 3.4% of placebo, all of which were mild. Taken together, the trial defines a microbiome-related signature for EcN benefit in acute paediatric diarrhoea: a short-duration watery stool illness, mostly viral or unspecified, in otherwise healthy children, treated early with a 10⁸ CFU/ml EcN suspension, resulting in faster stool normalization and better parent-judged health.

Key implications

Clinicians managing infants and toddlers with acute diarrhea can add Escherichia coli Nissle 1917 as an oral suspension to standard care to reduce illness duration by about two days, which is clinically relevant in children at risk of dehydration and for alleviating parental anxiety. The effect size is larger than that reported for many Lactobacillus-based products, so EcN is a reasonable first probiotic choice where it is licensed. Because EcN did not clear pathogens more effectively than the placebo, its benefit likely stems from barrier reinforcement, antimicrobial peptide release, and immune calming, all of which are consistent with previous EcN work. These mechanisms make EcN useful across both viral and nonspecific episodes. The study also reassures us about safety in very young children, supporting early-life probiotic strategies and providing human data for microbiome databases that link EcN to rapid recovery phenotypes in acute enteric infections.