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 habored 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. 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.” 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” were mainstream, and still benefiting 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. 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. EcN’s biofilm formation capabilities further enhance its probiotic role. EcN secretes inhibitory factors beyond microcins that block pathogen invasion into intestinal epithelial cells. 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. 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

Clinical Applications and Health Benefits

Over decades of study and clinical use, E. coli Nissle 1917 has demonstrated efficacy in a variety 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. Clinical trials have shown that E. coli Nissle is effective in maintaining remission in UC patients, on par with standard medication (5-ASA mesalazine). 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 UC maintenance therapy. For example, a landmark study found EcN could keep UC patients in remission as successfully as mesalamine, highlighting its anti-inflammatory benefits. EcN likely helps by normalizing the gut flora and reducing intestinal inflammation in UC. This offers patients a drug-free option (a live biotherapeutic) 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. Some studies and patient trials report that E. coli Nissle 1917 can alleviate IBS symptoms such as abdominal pain, bloating (meteorism), and irregular bowel habits in a subset of patients. In a multicenter trial, a majority of IBS patients showed symptom improvement after 4 weeks of Mutaflor (EcN) therapy, with reduced pain scores and improved quality of life.Those IBS patients whose condition onset followed infection or antibiotic use seem to benefit the most. The German national guidelines (DGVS) explicitly list probiotics like E. coli Nissle 1917 as a treatment option for IBS alongside dietary and other interventions. 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. Historically, Nissle’s concept was to use EcN to prevent or treat infectious diarrhea, and indeed it has been used for acute gastroenteritis and dysentery with success. More recently, research showed that EcN can reduce colonization by pathogens like Salmonella (as discussed, via iron competition). EcN has also been tested to prevent antibiotic-associated diarrhea and traveler’s diarrhea. As a probiotic, it helps restore microbial balance after antibiotics and occupies niches that might otherwise be taken by opportunistic bugs. Some trials indicate taking EcN can lower the risk or duration of diarrhea in such contexts, though results can depend on the specific pathogen. Overall, EcN acts as a biological barrier against GI infections – essentially pushing out the “bad bugs” by competing for resources and producing antimicrobial factors.

Chronic Constipation

Interestingly, E. coli Nissle 1917 has been used to manage chronic constipation as well. 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. The proposed explanation is that EcN’s metabolic byproducts (like short-chain fatty acids, e.g. acetic acid) can stimulate colonic movement and its restoration of a healthy microbiota may improve gut motility. By enhancing peristalsis and stool consistency, EcN offers a probiotic approach to relieving constipation without harsh laxatives.

Urinary Tract Infection Prevention

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. These biofilms prevent the colonization of Enterococcus faecalis, a major pathogen involved in catheter-related UTIs. 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 has gained attention for its potential role in oncology. The strain can colonize tumor sites and thrive in hypoxic environments, typical of many tumors. EcN’s fitness factors, such as microcins, siderophores, cellulose-based biofilms, and adhesins, allow it to outcompete other bacteria in tumor microenvironments. These factors help EcN establish itself within tumors, contributing to its ability to survive and proliferate in challenging conditions. EcN’s microcins act as antimicrobial peptides, targeting tumor-associated bacteria that may influence cancer progression. EcN’s siderophores support its survival by scavenging iron, which is often limited in tumor sites. Its rapid clearance from systemic circulation due to serum sensitivity makes EcN a safe candidate for clinical use, minimizing the risk of off-target colonization.

Respiratory Infections in Preterm Infants

A pilot study in late preterm newborns showed that EcN prophylaxis significantly reduced episodes of acute respiratory infections and hospitalisations within the first year of life, with no adverse effects. Although the exact mechanisms are unclear, gut microbiota modulation may influence systemic immunity and the gut–lung axis.

Diverticular Disease

EcN has been explored in the context of diverticulosis and mild diverticulitis. Uncomplicated diverticular disease (which often involves gut flora imbalance and low-grade inflammation) may benefit from EcN’s anti-inflammatory and microbiome-modulating effects. Some clinicians use Mutaflor to help stabilize the gut environment in patients with diverticular disease, potentially reducing flare-ups or symptoms like pain and bloating. While more research is needed, this represents another potential niche where EcN’s probiotic action can support intestinal health.

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. 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 a number of countries worldwide, including Canada, much of Europe, and parts of Asia and Australia. In these regions, it’s used by gastroenterologists and general practitioners alike as a treatment or adjunct for the conditions mentioned (UC, IBS, etc.). Notably, Mutaflor remains the only probiotic product on the market that contains EcN strain 1917 as its active ingredient. This exclusivity owes to the proprietary nature of the strain and its long history with Ardeypharm (the company that manufactures Mutaflor in Germany). In the United States, however, E. coli Nissle 1917 is not readily available. Regulatory hurdles (specifically, changes in 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 as well, especially given its documented benefits.

Current Biotechnology and Innovations

Beyond its traditional use as an off-the-shelf probiotic, E. coli Nissle 1917 has stepped into the spotlight of modern biotechnology and synthetic biology. 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. We are already witnessing this prophecy in action with clinical trials of engineered EcN strains for metabolic and infectious 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 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 safe, effective, and 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.

References

^[6] Escherichia coli strain Nissle 1917—from bench to bedside and back: history of a special Escherichia coli strain with probiotic properties

^[7] Escherichia coli Nissle 1917 Inhibits Clostridium perfringens Growth and Modulates Inflammation

^[8] The non-pathogenic Escherichia coli strain Nissle 1917 – features of a versatile probiotic

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^[9] 100 years of E. coli strain Nissle 1917

References

1. Ulrich Sonnenborn,. Escherichia coli strain Nissle 1917—from bench to bedside and back: history of a special Escherichia coli strain with probiotic properties,. (FEMS Microbiology Letters, Volume 363, Issue 19, October 2016, fnw212,)
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)
4. 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.)
5. 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.)
6. Ulrich Sonnenborn,. Escherichia coli strain Nissle 1917—from bench to bedside and back: history of a special Escherichia coli strain with probiotic properties,. (FEMS Microbiology Letters, Volume 363, Issue 19, October 2016, fnw212,)
7. 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)
8. 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.)
9. 100 years of E. coli strain Nissle 1917. Ulrich Sonnenborn. (Oxford University Press's Academic Insights for the Thinking World, April 28th 2017)