A double-blind placebo-controlled trial to study therapeutic effects of probiotic Escherichia coli Nissle 1917 in subgroups of patients with irritable bowel syndrome Original paper

What was studied?

Escherichia coli Nissle 1917 irritable bowel syndrome therapy was tested in a randomized double-blind placebo-controlled 12-week trial to see whether a single well-characterized Gram-negative probiotic could improve symptoms in adults who met Rome II criteria for IBS and to identify the subgroup most likely to benefit, especially those with disturbed enteric microflora after gastroenteritis or antibiotic exposure, and the investigators used global patient satisfaction (IMPSS), symptom diaries, and IBS-related quality-of-life scores to compare EcN with placebo while keeping background medication stable. Hence, the paper links a clinical signal to the known EcN mechanisms of action, such as defensin induction, epithelial barrier support, and antagonism of enteroinvasive bacteria. These mechanisms are particularly relevant to microbiome-signature work, where postinfectious IBS often exhibits loss of stability and low-grade immune activation.

Who was studied?

A total of 120 adults aged 18–65 years with IBS diagnosed by Rome II, with symptoms for about a decade on average, were enrolled and randomized 1:1 to daily EcN (MUTAFLOR; 2.5–25×10⁹ CFU per capsule with an initial low dose then two capsules daily) or visually identical placebo for 12 weeks, most were women, bowel habit was mixed across constipation-predominant, diarrhoea-predominant, and alternating patterns, organic disease had been excluded by the Kruis score, and a prespecified subgroup had either bacterial gastroenteritis or an antibiotic course shortly before IBS onset, a group interpreted as having altered enteric microflora and therefore a higher chance of responding to a microbiota-directed intervention.

Most important findings

Escherichia coli Nissle 1917 irritable bowel syndrome treatment produced a higher overall responder rate than placebo, but the difference reached significance only in weeks 10 and 11, which means the effect was modest and slow, yet clinically detectable, and at week 12 the EcN group still showed an 11–12% advantage that did not reach p<0.05, while the key result came from the subgroup with prior gastroenteritis and or antibiotics where response reached about 60% on EcN versus about 14% on placebo, a 45.7 percentage-point gain that was statistically significant, showing that when IBS followed a presumed dysbiosis EcN could restore comfort much better than placebo; symptom tracking showed that both groups improved in pain intensity, duration, and frequency, confirming the significant placebo component in IBS trials, but some symptoms such as meteorism and nausea improved only with EcN, which matches EcN’s known epithelial and motility-modulating actions, and safety, laboratory parameters, and tolerance were as good as placebo, so the microbiome-relevant signature that emerges is IBS of postinfectious or postantibiotic origin, with gas-related symptoms, in a host who can support colonization by a defensin-inducing, pathogen-blocking E. coli.

Key implications

Clinicians should not expect Escherichia coli Nissle 1917 to relieve all-comers with IBS, but in patients whose IBS started after a clear enteric hit or antibiotic disruption, and who still report bloating or nausea, a 12-week EcN course is justified because the trial shows the most significant effect there, and this matches the biologic model in which EcN occupies mucosal niches, blocks pathogen invasion, stimulates β-defensins, and calms low-grade immune signals that are described in postinfectious IBS, so for microbiome-signature databases the paper supports tagging EcN to IBS cases with antecedent dysbiosis rather than to idiopathic IBS, and it also reinforces the need for long enough treatment windows, around 10–12 weeks, for probiotic effects to become distinct from placebo.