E. coli Nissle 1917
The Probiotic That Is a "Bad" Bacterium
Evidence grade 3 of 5, Mixed. Read how the Atlas grades evidence.
6 human trials, about 150 studies, Thousands. The written rationale for this grade is still being prepared.
- FDA
- Sold as Mutaflor; regulatory status varies by country
- WADA
- Not prohibited
Reference only. Not medical advice.
What can go wrong
Generally well tolerated in trials, with mild, transient GI effects (gas, bloating, occasional loose stools) most commonly reported. As a live E. coli strain it warrants caution in severely immunocompromised people, and its genome carries the pks island encoding colibactin, a genotoxin whose long-term relevance is debated, so it is best viewed as a specific clinical tool rather than a casual daily supplement. It is a prescription product in several countries and is not sold in the United States, and formal ulcerative colitis management, including any use during pregnancy, in childhood, or alongside other therapy, should be directed by a qualified gastroenterologist or physician who can weigh risks and benefits for the individual.
Escherichia coli Nissle 1917 (EcN, sold as Mutaflor) is one of the oldest and most counterintuitive probiotics: a benign strain of a species better known for its dangerous relatives. German physician Alfred Nissle isolated it in 1917 from a soldier who resisted dysentery, and it carries no classical virulence genes. Its strongest evidence is for maintaining remission in ulcerative colitis, where three double-blind equivalence trials found it non-inferior to standard mesalazine, though later meta-analysis and a Cochrane review rated the pooled data as limited and low certainty. It is a prescription drug in several countries and is not sold in the United States. It is also the entry that shows probiotic safety is a strain-level question, and it carries an unresolved wrinkle: the same genome hosts the pks island encoding colibactin, a genotoxin that some researchers argue cannot be cleanly separated from its benefit.
A century-old probiotic strain of E. coli, evidence-backed for maintaining ulcerative colitis remission, as effective as standard mesalamine in trials.
What people take it for
These are the reasons people give for taking it. They are not effects it has been shown to have.
What people get wrong
Often saidE. coli is always dangerous, so an E. coli probiotic makes no sense
ActuallyWhether E. coli harms is strain-specific. Nissle 1917 carries no classical virulence genes and produces no known toxins, and it has real equivalence-trial evidence for ulcerative colitis maintenance, while other E. coli strains cause serious illness. That contrast is exactly why strain identity, not species, is what matters (World J Gastroenterol review; PMC4917610).
Often saidProbiotics never match real drugs for disease
ActuallyFor maintaining ulcerative colitis remission, EcN was non-inferior to standard mesalazine across three double-blind trials, most notably Kruis 2004 (Gut, n=327, equivalence p=0.003). That is a rare case of a probiotic matching a conventional therapy for a defined use, though it is equivalence rather than superiority and the pooled data remain limited.
Often saidA century-old probiotic is fully understood and obviously safe
ActuallyLong use is not the same as a clean safety file. Sequencing revealed EcN hosts the pks island encoding colibactin, a genotoxin linked to colorectal-cancer mutations, and some researchers report its genotoxicity cannot be dissociated from its benefit (Olier 2012, Gut Microbes; Nougayrede 2021, mSphere). The clinical trial safety record is reassuring, but the mechanism debate is genuinely open.
Often saidIf it works this well, you can just buy it in the US
ActuallyEcN is a prescription drug (Mutaflor) in several countries and is not distributed in the United States; a 2011 New Dietary Ingredient path did not open US supplement sale. Strong evidence for a specific indication does not guarantee availability.
Who profits, and who pushes back
Jean-Philippe Nougayrede and colleagues
Nissle 1917 produces the genotoxin colibactin during gut colonization and induces DNA damage; administration as a probiotic or as a chassis to deliver therapeutics might exert long-term adverse effects and should be considered in a risk-versus-benefit evaluation.
Maiwenn Olier and colleagues
In their DSS-colitis model, removing the colibactin pathway (clbA) abolished genotoxicity but also abolished protection, leading them to conclude the probiotic activity of E. coli Nissle 1917 cannot be dissociated from its genotoxicity.
Cochrane IBD review authors (Iheozor-Ejiofor and colleagues)
For probiotics in maintaining ulcerative colitis remission, the certainty of evidence is low and there is insufficient evidence to draw firm conclusions, reflecting a lack of well-designed randomized trials.
Ardeypharm (Mutaflor)
Sells this. Has a commercial interest in a product sold as this compound, as of July 2026.
Markets the strain, mainly in Germany; the UC evidence is genuine but commercial availability is uneven.
IBD researchers
Provide the RCT evidence for maintenance of remission comparable to mesalamine.
European gastroenterologists
Use Nissle in selected UC patients, especially where standard therapy is not tolerated.
Where the research comes from
| Place | Share of published research |
|---|---|
| Germany | 45% |
| Europe | 35% |
| Other | 20% |
Research published from: Germany, Europe, Global.
How we got here
During the First World War, the German physician Alfred Nissle isolated an E. coli strain from the stool of a soldier who, unlike comrades deployed to a Shigella-heavy region of the Balkans (Dobruja), had not developed dysentery. Nissle reasoned the man carried an antagonistically strong strain and, working near Freiburg in the pre-antibiotic era when enteric infection devastated troops, developed it into the drug Mutaflor. That strain, E. coli Nissle 1917 (serotype O6:K5:H1), became one of the longest-used probiotics and later one of the best-studied, with equivalence trials in the 1990s and 2000s establishing it as non-inferior to mesalazine for maintaining ulcerative colitis remission. Modern genome work found no classical virulence genes yet did find the pks island encoding colibactin, reframing an old remedy as a live-strain question of risk and benefit. It remains a standout example of why bacterial reputations are strain-level, not species-level, and, more recently, a chassis for engineered live therapeutics.
- 1917Alfred Nissle isolates the protective E. coli strain from a soldier near Freiburg and develops it into the drug Mutaflor
- 1997Kruis pilot RCT signals equivalence to mesalazine for maintaining ulcerative colitis remission
- 1999Rembacken publishes a non-inferiority trial (Lancet, n=120) showing EcN is not inferior to mesalazine for preventing UC relapse
- 2004Kruis publishes the largest equivalence trial (Gut, n=327), confirming EcN maintenance is equivalent to standard mesalazine
- 2007Henker RCT (n=113) reports EcN shortens acute diarrhea in infants and toddlers
- 2011US distribution ends after a New Dietary Ingredient notification to the FDA does not clear the way for sale as a supplement
- 2012Researchers report the strain's genotoxicity (colibactin) cannot be cleanly separated from its probiotic activity (Gut Microbes)
- 2015Systematic review and meta-analysis (6 trials, 719 patients) finds EcN comparable to mesalazine but with wide confidence intervals
- 2020Cochrane review rates probiotic UC-maintenance evidence low certainty and calls it insufficient for firm conclusions
- 2024Synlogic discontinues Phase 3 of its EcN-engineered PKU therapy (SYNB1934) for lack of efficacy, then winds down operations
At a glance
- Isolated
- Alfred Nissle, 1917
- Species
- E. coli (a benign strain)
- Best evidence
- Maintaining ulcerative colitis remission
- Product
- Mutaflor
What this entry does not yet cover
What follows is unfinished work on our side, not a finding about E. coli Nissle 1917. A short entry is not a safe entry.
- Cost and market. We have not documented what it sells for or who sells it.
- Supply chain. We have not mapped where it is made.
- Who uses it. We have not documented the user groups.
- What could change. No forward-looking summary yet.
- How it compares. We have not set it against the alternatives.
- Children and teenagers. We have not checked what is known about younger people.
Sources
Kruis 2004 equivalence RCT (Gut, n=327): EcN non-inferior to mesalazine for UC maintenance, per-protocol relapse 36.4% vs 33.9%, equivalence p=0.003
Rembacken 1999 non-inferiority trial (Lancet, n=120): EcN not inferior to mesalazine for preventing UC relapse
2015 systematic review and meta-analysis (6 trials, 719 patients): EcN comparable to mesalazine, pooled OR 0.92 (95% CI 0.15-9.66)
2020 Cochrane review (4 studies, 587 participants): low-certainty, insufficient evidence for firm conclusions on probiotics for UC maintenance
Cochrane Database Syst Rev (Iheozor-Ejiofor et al. 2020) via PubMed record
Mechanisms (microcins/iron systems, F1C fimbriae, flagellin adhesin, ZO-1/ZO-2 tight junctions, defensin induction, cytokine modulation), serotype O6:K5:H1, no known toxins, ECCO recommends EcN as only probiotic alternative to mesalazine for UC maintenance
Genotoxicity of EcN cannot be dissociated from its probiotic activity; removing colibactin pathway (clbA) abolished protection in DSS colitis
EcN produces colibactin in the gut, induces DNA interstrand cross-links and mutations; authors urge risk-benefit evaluation before probiotic or chassis use
Historical isolation in 1917 by Alfred Nissle from a soldier near Freiburg resistant to dysentery in the Balkans; development into Mutaflor; no virulence genes
Oxford University Press blog, '100 years of E. coli strain Nissle 1917'
Henker 2007 RCT (n=113): EcN suspension shortens acute diarrhea in infants and toddlers (2.5 vs 4.8 days, p=0.0007)
US regulatory status: 2011 New Dietary Ingredient notification for E. coli strain Nissle 1917 / Mutaflor (Medical Futures Inc.); product not distributed in the US thereafter
Engineered EcN chassis (Synlogic SYNB1934/labafenogene) Phase 3 PKU trial discontinued Feb 2024 for lack of efficacy, not safety; company wound down
Phase 2 data for EcN-engineered PKU strains (SYNB1618/SYNB1934) lowering plasma phenylalanine; no serious adverse events