E. coli Nissle 1917

Overview

Escherichia coli Nissle 1917 (EcN) is a unique probiotic strain of E. coli with a remarkable history and multifaceted health benefits. Unlike its pathogenic cousins, this strain is a harmless commensal bacterium that can promote gut health and combat intestinal pathogens.^[1] Discovered over a century ago, E. coli Nissle 1917 has been extensively studied as a therapeutic probiotic and is the active ingredient in the probiotic product Mutaflor.^[2] With its ability to colonize the human gut and outcompete disease-causing microbes, EcN has found applications ranging from the management of gastrointestinal diseases to cutting-edge biotechnology.

Historical Background of E. coli Nissle 1917

E. coli Nissle 1917 dates back to World War I and highlights one of the earliest examples of probiotic therapy. The probiotic strain was discovered by Alfred Nissle in 1917, who isolated it from the stool of a World War I soldier who had remained healthy despite a dysentery outbreak afflicting his comrades.^[3] Nissle suspected the soldier’s gut harbored a protective microbe. Indeed, the isolated bacterium showed strong antagonistic activity against Shigella and other intestinal pathogens in lab tests.^[4] Nissle named it “strain Nissle 1917,” marking the year of discovery. In 1917, Alfred Nissle immediately recognized the therapeutic potential of this strain. He developed it into a probiotic medicine called Mutaflor, introducing it into medical practice that same year.^[5] Mutaflor (containing EcN) has been available in the German pharmaceutical market ever since, making it one of the oldest probiotic remedies in continuous use. For decades, it was used in Germany and other countries to treat bacterial diarrhea and gut inflammation, even as antibiotics rose to prominence.^[6] Although overshadowed by antibiotics in the mid-20th century, E. coli Nissle saw a renaissance in the late 20th century as interest in probiotics and microbiome-friendly therapies grew. Researchers like Ulrich Sonnenborn chronicled “100 years of research” on this strain, noting it is “probably the most intensely investigated bacterial strain today.”^[7] This rich history cements E. coli Nissle 1917’s reputation as a pioneering probiotic, discovered in the crucible of war, developed into a medication long before probiotics became mainstream, and continues to benefit human health over a century later.

Probiotic Mechanisms of E. coli Nissle 1917

E. coli Nissle 1917 (EcN) is a potent probiotic strain that supports gut health by employing several complex and complementary mechanisms. One of the key actions is iron sequestration, where EcN produces multiple siderophores and iron-uptake systems to outcompete pathogenic bacteria that rely on iron for growth.^[8] Another mechanism is microcin production; EcN produces antimicrobial peptides such as MccM and MccH47 that specifically target and inhibit the growth of competing pathogens, including other Enterobacteriaceae.^[9] The probiotic also plays a significant role in immune modulation, where it interacts with host immune cells, balancing the immune response by reducing inflammation and enhancing the gut barrier integrity. EcN’s ability to modulate immune functions, stimulate protective molecules, and strengthen the gut lining is crucial in maintaining a hostile environment for pathogens while promoting health.^[10] Together, these combined actions allow EcN to compete with harmful microbes, safeguard the gut ecosystem, and support intestinal health.

Mechanisms of Pathogen Competition and Probiotic Action by E. coli Nissle 1917

Mechanism	Action by EcN
Iron Sequestration	EcN produces siderophores and multiple metal-uptake systems (e.g., FepA, FhuA) that bind and assimilate zinc and iron, depriving competing pathogens of this essential nutrient.[11] This effect is beneficial in inflammatory gut conditions where pathogens depend on metals.
Microcin Production	EcN synthesizes antimicrobial peptides such as MccM and MccH47.[12] These microcins are conjugated to siderophores and specifically target the cell membranes of competing bacteria, thereby disrupting essential processes.[13]
Biofilm Formation	EcN produces F1C fimbriae and cellulose, enabling it to form stable biofilms on the intestinal mucosa.[14] This biofilm physically excludes enteric pathogens, preventing their adhesion and colonization in the gut.
Secreted Inhibitory Factors	EcN secretes unidentified factors that directly inhibit the invasion of enteric pathogens such as Salmonella, Yersinia, Shigella, Legionella, and Listeria into epithelial cells.[15] These factors work independently of microcin production, providing an additional layer of protection.
Immune Modulation	EcN modulates immune responses by promoting the production of anti-inflammatory cytokines and enhancing the gut’s physical barrier.[16] It increases the expression of tight junction proteins and β-defensins, and modulates the activity of dendritic cells and natural killer (NK) cells, thereby balancing the immune response to favor health while suppressing excessive inflammation.[17]

Clinical Applications and Health Benefits

Over the course of decades of study and clinical use, E. coli Nissle 1917 has demonstrated efficacy in a range of gastrointestinal conditions. Its ability to modulate gut microbiota and immunity makes it a versatile therapeutic option. Key clinical applications of EcN include:

Ulcerative Colitis (UC)

One of the most significant uses of EcN is in inflammatory bowel disease, particularly ulcerative colitis.^[18] Clinical trials have demonstrated that E. coli Nissle is effective in maintaining remission in UC patients, comparable to standard medication (5-ASA mesalazine).^[19] In fact, the strain is the only probiotic recommended by the European Crohn’s and Colitis Organisation (ECCO) as an effective alternative to mesalazine for maintaining UC. For example, a landmark study found EcN could keep UC patients in remission as successfully as mesalamine, highlighting its anti-inflammatory benefits.^[20] EcN likely helps by normalizing the gut flora and reducing intestinal inflammation in UC. This offers patients a drug-free option to manage a chronic inflammatory condition, which is especially valuable for those who cannot tolerate or prefer to minimize traditional medications.

Irritable Bowel Syndrome (IBS)

Probiotics are often explored for IBS relief, and EcN is no exception. In a randomised controlled trial involving patients with IBS, EcN significantly increased responder rates compared with placebo.^[21] In a multicenter trial, a majority of IBS patients experienced symptom improvement after 4 weeks of Mutaflor (EcN) therapy, characterized by reduced pain scores and improved quality of life.^[22] Those IBS patients whose condition onset followed infection or antibiotic use seem to benefit the most. While IBS is complex and responses vary, EcN’s combined effects on gut flora balance and immune modulation make it a promising adjunct therapy for managing IBS symptoms in some individuals.

Infectious Diarrhea and Prevention of Gut Infections

The antagonistic power of EcN against pathogens translates into protection against certain diarrheal illnesses.^[23] Historically, Nissle’s concept was to use EcN to prevent or treat infectious diarrhea, and indeed it has been used successfully for acute gastroenteritis and dysentery.^[24] More recently, research has shown that EcN can reduce colonization by pathogens such as Salmonella.^[25] As a probiotic, it helps restore microbial balance after antibiotics and occupies niches that opportunistic pathogens might otherwise take. Some trials suggest that taking EcN can lower the risk or duration of diarrhea in specific contexts, although the results may depend on the particular pathogen. Overall, EcN acts as a biological barrier against GI infections by competing for resources and producing antimicrobial factors.

Chronic Constipation

Interestingly, E. coli Nissle 1917 has also been used to manage chronic constipation. It may seem counterintuitive (since E. coli is not a laxative), but case studies and a 1990s trial found that EcN supplementation improved bowel regularity in people with slow transit constipation.^[26] The proposed explanation is that EcN’s metabolic byproducts, such as short-chain fatty acids (e.g., acetic acid), can stimulate colonic movement, and their restoration of a healthy microbiota may improve gut motility.^[27] By enhancing peristalsis and improving stool consistency, EcN offers a probiotic approach to relieving constipation without the need for laxatives.

Catheter-associated urinary tract infections (CAUTIs)

Urinary tract infections (UTIs), especially those associated with indwelling catheters, are common in hospital settings. E. coli Nissle 1917 (EcN) has shown potential in preventing catheter-associated UTIs by forming biofilms on mannoside-functionalized silicone catheters.^[28] These biofilms prevent the colonization of Enterococcus faecalis, a major pathogen involved in catheter-related UTIs.^[29] The biofilm formation by EcN physically blocks pathogens from adhering to catheter surfaces, providing a protective barrier. This could reduce the incidence of UTIs in patients who need long-term catheterization.

Anti-Tumor Applications

EcN’s serum sensitivity, resulting from a mutation in its lipopolysaccharide coat, facilitates rapid clearance from the bloodstream, leading to high tumor colonization and minimal off-target tissue colonization.^[30][31] Its fitness factors, such as microcins and siderophores, allow it to outcompete other bacteria and thrive in the hypoxic conditions typical of tumors.^[32] These properties make EcN a promising candidate for clinical oncology, with minimal risk of systemic side effects or off-target effects. Additionally, EcN’s lack of antibiotic resistance further supports its safety as a therapeutic option in cancer treatments.

Respiratory Infections in Preterm Infants

A pilot study on late preterm newborns showed that supplementing with the probiotic E. coli strain Nissle 1917 (EcN) significantly lowered acute respiratory infections (ARIs) and hospitalizations in the first year of life, with no reported adverse effects.^[33] While the study’s direct impact during the first month of life was strong, the long-term reduction was more of a trend. These findings suggest EcN may be a promising and safe prophylactic measure for vulnerable newborns, though larger trials are needed to confirm the results. 

Product Development and Availability

The primary commercial formulation of E. coli Nissle 1917 is Mutaflor, a probiotic capsule containing live EcN. First launched by Nissle in 1917, Mutaflor has the distinction of being a registered medicinal probiotic in Germany for over a century.^[34] Unlike many yogurts or dietary supplements, Mutaflor is regulated as a pharmaceutical in certain countries, ensuring consistent potency (each capsule typically contains 2.5–25 billion viable EcN cells). This strain-specific probiotic is produced under controlled conditions to preserve its unique properties.

Mutaflor is available in several countries worldwide, including Canada, most of Europe, and parts of Asia and Australia. In these regions, it is used by gastroenterologists and general practitioners alike as a treatment or adjunct for the conditions mentioned (e.g., UC, IBS).^[35] Notably, Mutaflor remains the only probiotic product on the market that contains EcN strain 1917 as its active ingredient. In the United States, however, E. coli Nissle 1917 is not readily available. Regulatory hurdles (specifically, changes in the FDA’s dietary supplement guidelines around 2011) prevented Mutaflor from being sold as a supplement in the US. As a result, US patients interested in EcN have had to obtain it from abroad or via clinical trials. Nonetheless, in an era of increasing interest in the microbiome, there is hope that EcN or similar live biotherapeutics may eventually find a place in the US market, especially given their documented benefits.

Current Biotechnology and Innovations

Beyond its traditional use as an off-the-shelf probiotic, E. coli Nissle 1917 has emerged as a key player in modern biotechnology and synthetic biology.^[36] Scientists are leveraging EcN’s friendly nature and gut-colonizing ability to create engineered probiotics that perform novel therapeutic functions. The ongoing innovations ensure that E. coli Nissle 1917 remains at the cutting edge of probiotic therapy. As Ulrich Sonnenborn predicted, EcN derivatives will be used as carriers of bioactive molecules and novel therapeutics in the future^[37]. We are already witnessing this prophecy in action with clinical trials of engineered EcN strains for metabolic and infectious diseases.

Biotechnology Applications	Research Directions
Genetically Engineered Therapeutics	Researchers have modified EcN to deliver drugs, enzymes, or signals inside the human body. For example, an engineered EcN strain has been developed to aid in the treatment of the metabolic disorder phenylketonuria (PKU).[38] In this case, EcN was given new genes to metabolize phenylalanine, effectively turning it into a living medicine in the gut. Another engineered EcN, developed by the company Synlogic (code-named SYNB1020), was programmed to consume ammonia in the intestines as a novel treatment for hyperammonemia (excess ammonia in blood due to liver disease). In preclinical models, this modified EcN lowered toxic ammonia levels and improved survival.[39]
Targeted Anti-Infectives	Building on EcN’s innate antagonism toward microbes, scientists have taken it a step further by engineering EcN to seek and destroy specific pathogens. In a notable 2017 study, researchers inserted genetic circuits into EcN, enabling it to sense the presence of Pseudomonas aeruginosa and then secrete tailored anti-Pseudomonas factors.[40] The engineered EcN not only killed P. aeruginosa in lab cultures but also successfully cleared and prevented Pseudomonas infections in animal models (mice and even C. elegans worms).
Live Vaccine Vectors	Because EcN is non-pathogenic yet immunogenic enough to stimulate the immune system mildly, researchers have proposed using it as a vaccine vector.[41] The idea is to genetically modify EcN, turning it into an oral vaccine that exposes the gut immune system to those antigens and triggers protective immunity.[42] Since EcN can survive passage through the stomach and colonize the gut, it could present antigens over an extended period, potentially yielding a strong immune response. This approach is still largely experimental, but it presents EcN’s versatility as a vehicle for antigen delivery in diseases.

E. coli Nissle 1917 stands out as a remarkable probiotic strain that bridges historical medicine and contemporary science. For over 100 years, it has helped prevent and treat intestinal ailments by outcompeting pathogens and reinforcing gut health. Its proven clinical benefits in health conditions have made it a staple probiotic for physicians in many parts of the world. At the same time, the unique characteristics it possesses inspire the development of new biotech therapies. The story of EcN illustrates the broader promise of the microbiome: that our bacterial allies can be harnessed to improve health in ways conventional drugs often cannot. Accessible to the general public yet of great interest to researchers, E. coli Nissle 1917 exemplifies how a well-researched probiotic can be both safe and effective, while also being innovative. As research progresses and awareness grows, EcN’s legacy is likely to expand, cementing its role as both a therapeutic workhorse and a platform for next-generation biotechnologies.

Research Feed

References

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2. Yanlong Jiang, Qingke Kong, Kenneth L. Roland, Amanda Wolf, Roy Curtiss. Multiple effects of Escherichia coli Nissle 1917 on growth, biofilm formation, and inflammation cytokines profile of Clostridium perfringens type A strain CP4. (Pathogens and Disease, Volume 70, Issue 3, April 2014, Pages 390–400)
3. 100 years of E. coli strain Nissle 1917. Ulrich Sonnenborn. (Oxford University Press's Academic Insights for the Thinking World, April 28th 2017)
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8. Siderophore-mediated zinc acquisition enhances enterobacterial colonization of the inflamed gut.. Behnsen, J., Zhi, H., Aron, A.T. et al.. (Nat Commun 12, 7016 (2021).)
9. Microcins mediate competition among Enterobacteriaceae in the inflamed gut.. Sassone-Corsi, M., Nuccio, P., Liu, H., Hernandez, D., Vu, C. T., Takahashi, A. A., Edwards, R. A., & Raffatellu, M. (2016).. (Nature, 540(7632), 280.)
10. Role and mechanisms of action of Escherichia coli Nissle 1917 in the maintenance of remission in ulcerative colitis patients: An update.. Scaldaferri, F., Gerardi, V., Mangiola, F., Lopetuso, L. R., Pizzoferrato, M., Petito, V., Papa, A., Stojanovic, J., Poscia, A., Cammarota, G., & Gasbarrini, A. (2016).. (World Journal of Gastroenterology, 22(24), 5505.)
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16. Role and mechanisms of action of Escherichia coli Nissle 1917 in the maintenance of remission in ulcerative colitis patients: An update.. Scaldaferri, F., Gerardi, V., Mangiola, F., Lopetuso, L. R., Pizzoferrato, M., Petito, V., Papa, A., Stojanovic, J., Poscia, A., Cammarota, G., & Gasbarrini, A. (2016).. (World Journal of Gastroenterology, 22(24), 5505.)
17. Escherichia coli Nissle 1917 protects gnotobiotic pigs against human rotavirus by modulating plasmacytoid dendritic and natural killer cell responses.. Vlasova, A. N., Shao, L., Kandasamy, S., Fischer, D. D., Rauf, A., Langel, S. N., Chattha, K. S., Kumar, A., Huang, C., Rajashekara, G., & Saif, L. J. (2016).. (European Journal of Immunology, 46(10), 2426.)
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20. Role and mechanisms of action of Escherichia coli Nissle 1917 in the maintenance of remission in ulcerative colitis patients: An update.. Scaldaferri, F., Gerardi, V., Mangiola, F., Lopetuso, L. R., Pizzoferrato, M., Petito, V., Papa, A., Stojanovic, J., Poscia, A., Cammarota, G., & Gasbarrini, A. (2016).. (World Journal of Gastroenterology, 22(24), 5505.)
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31. Engineering tumor-colonizing E. coli Nissle 1917 for detection and treatment of colorectal neoplasia. Gurbatri, C. R., Radford, G. A., Vrbanac, L., Im, J., Thomas, E. M., Coker, C., Taylor, S. R., Jang, Y., Sivan, A., Rhee, K., Saleh, A. A., Chien, T., Zandkarimi, F., Lia, I., M Lannagan, T. R., Wang, T., Wright, J. A., Kobayashi, H., Ng, J. Q., . . . Danino, T. (2024). Engineering tumor-colonizing E. Coli Nissle 1917 for detection and treatment of colorectal neoplasia.. (Nature Communications, 15, 646.)
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33. Prophylaxis of acute respiratory infections via improving the immune system in late preterm newborns with E. coli strain Nissle 1917: a controlled pilot trial.. Aryayev, M.L., Senkivska, L.I., Bredeleva, N.K. et al.. (Pilot Feasibility Stud 4, 79 (2018))
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35. Benefits and concerns of probiotics: an overview of the potential genotoxicity of the colibactin-producing Escherichia coli Nissle 1917 strain.. Falzone, L., Lavoro, A., Candido, S., Salmeri, M., Zanghì, A., & Libra, M. (2024).. (Gut Microbes, 16(1).)
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37. The non-pathogenic Escherichia coli strain Nissle 1917 – features of a versatile probiotic.. Sonnenborn, U., & Schulze, J. (2009).. (Microbial Ecology in Health and Disease, 21(3–4), 122–158.)
38. Improvement of a synthetic live bacterial therapeutic for phenylketonuria with biosensor-enabled enzyme engineering.. Adolfsen, K.J., Callihan, I., Monahan, C.E. et al.. (Nat Commun 12, 6215 (2021).)
39. An engineered E. coli Nissle improves hyperammonemia and survival in mice and shows dose-dependent exposure in healthy humans. Caroline B. Kurtz et al. ,. (Sci. Transl. Med.11,eaau7975(2019))
40. Engineered probiotic Escherichia coli can eliminate and prevent Pseudomonas aeruginosa gut infection in animal models.. Hwang, I., Koh, E., Wong, A. et al.. (Nat Commun 8, 15028 (2017).)
41. The non-pathogenic Escherichia coli strain Nissle 1917 – features of a versatile probiotic.. Sonnenborn, U., & Schulze, J. (2009).. (Microbial Ecology in Health and Disease, 21(3–4), 122–158.)
42. Gut Microbiota-Based Immunotherapy: Engineered Escherichia coli Nissle 1917 for Oral Delivery of Glypican-1 in Pancreatic Cancer.. Vruzhaj, I., Gambirasi, M., Busato, D., Giacomin, A., Toffoli, G., & Safa, A. (2025).. (Medicina, 61(4), 633.)