Entry 29
Probiotic science page
Uses type 1 fimbriae and microcins to competitively exclude pathogens and maintain ulcerative colitis remission, with RCT evidence.
Overview
Escherichia coli Nissle 1917 (EcN) is a non-pathogenic probiotic strain. Alfred Nissle isolated it in 1917 from the feces of a healthy soldier during a shigellosis outbreak [1,5]. It is the active ingredient in Mutaflor (Ardeypharm GmbH, Germany). This is one of the oldest commercially available probiotic preparations [1]. EcN is distinguished from commensal and pathogenic E. coli by specific genomic features. These include multiple prophages, fitness islands, and the absence of virulence determinants [6]. RCTs have extensively studied it for ulcerative colitis (a type of inflammatory bowel disease) maintenance and constipation-predominant irritable bowel syndrome. It is increasingly studied as a chassis for engineered live biotherapeutics [1,2,5].
Mechanism
EcN antagonizes enteropathogens. It does this through production of microcins (class IIb bacteriocins) that inhibit related Enterobacteriaceae. It also competes for adhesion sites and nutrients [5,6]. The strain carries flagella and fimbriae. These enable intestinal colonization and sticking to cells lining the gut. It lacks the genes for Shiga toxin, alpha-hemolysin, and other classical E. coli virulence factors [6]. EcN induces epithelial beta-defensin-2 expression via flagellin-TLR5 signaling. This enhances mucosal innate immunity [5]. The genome encodes fitness-conferring genomic islands. These include the pks locus for colibactin and the clb gene cluster. They contribute to ecological competitiveness. They are absent in avirulent laboratory strains [6]. Researchers have engineered EcN for therapeutic delivery of STING agonists (SYNB1891). They have also engineered it for tumor-colonizing detection of colorectal neoplasia. This exploits its tumor-homing capacity [5] (clinical trial).
Health Benefits
A landmark double-blind, double-dummy RCT enrolled 327 patients. It demonstrated that EcN (200 mg/day) was equivalent to standard mesalazine (500 mg × 3/day) for maintaining remission in ulcerative colitis (a type of inflammatory bowel disease) over 12 months. Relapse rates were 36.4% vs. 33.9% (P = 0.003 for equivalence) [1] (RCT). A multicenter RCT enrolled Korean ulcerative colitis patients. It confirmed that Mutaflor as add-on to 5-ASA therapy improved clinical response and mucosal healing compared to 5-ASA alone [2] (RCT). A double-blind RCT enrolled Alzheimer’s disease patients. It showed that EcN reduced serum NOX2 levels and lipopolysaccharide. This suggests systemic anti-inflammatory effects [3] (RCT). Researchers engineered EcN into SYNB1891. This is an STING agonist-expressing strain. A Phase I trial tested it for advanced malignancies. It showed acceptable safety and preliminary anti-tumor activity [5] (Phase I clinical trial). In a Phase 1/2a study, an engineered EcN strain (SYNB1618) metabolized phenylalanine for treatment of phenylketonuria. This demonstrated proof-of-concept for metabolic engineering of probiotics [unverified: Puurunen et al. 2021, PMID 34294923, confirmed via esummary]. In term neonates, an RCT suggested benefit of EcN for gut colonization [unverified: Olbertz et al. 2023, PMID 36446590, confirmed via esummary].
Biology
Escherichia coli Nissle 1917 is a Gram-negative, motile rod. It grows with or without oxygen. It measures approximately 0.5 × 1-3 µm. It belongs to the family Enterobacteriaceae (now reclassified within the order Enterobacterales) within the phylum Pseudomonadota [6]. The genome is approximately 5.0 Mb. It has ~4,700 predicted coding sequences. It contains six prophage regions, the pks colibactin island, and multiple fitness islands. It lacks genes for Shiga toxin, intimin, and hemolysin [6]. EcN is catalase-positive, oxidase-negative, and indole-positive. It ferments glucose and lactose [6]. It is serotype O6:K5:H1. The K5 capsule is a key fitness factor for serum resistance and intestinal colonization [6]. EcN is non-invasive. It does not produce thermolabile or thermostable enterotoxins [6]. Its natural habitat is the human and mammalian intestinal tract. It colonizes transiently [6].
Bibliography
Kruis W, Fric P, Pokrotnieks J, et al. (2004). Maintaining remission of ulcerative colitis with the probiotic Escherichia coli Nissle 1917 is as effective as with standard mesalazine. Gut. 53(11):1617-1623. PMID: 15479682
Park SK, Kang SB, Kim S, et al. (2022). Additive effect of probiotics (Mutaflor) on 5-aminosalicylic acid therapy in patients with ulcerative colitis. Korean Journal of Internal Medicine. 37(5):949-957. PMID: 36068716
Loffredo L, Alfano AR, Ettorre E, et al. (2025). Effect of the probiotic Escherichia coli Nissle 1917 on serum levels of NADPH oxidase-2 and lipopolysaccharide in patients with Alzheimer’s disease. Journal of Alzheimer’s Disease. 106(2):774-782. PMID: 40420691
Gurbatri CR, Radford GA, Vrbanac L, et al. (2024). Engineering tumor-colonizing E. coli Nissle 1917 for detection and treatment of colorectal neoplasia. Nature Communications. 15(1):646. PMID: 38245513
Vaghela P, Dave B, Dabhade A, et al. (2026). Redrawing the gut map: evolving probiotic approaches to microbiota modulation in inflammatory bowel disease. Antonie Van Leeuwenhoek. 119(3):51. PMID: 41644858
Sun J, Gunzer F, Westendorf AM, et al. (2005). Genomic peculiarity of coding sequences and metabolic potential of probiotic Escherichia coli strain Nissle 1917 inferred from raw genome data. Journal of Biotechnology. 117(2):147-161. PMID: 15823404
Available Products
Mutaflor (Ardeypharm GmbH, Herdecke, Germany) is the primary commercial product containing viable EcN. It is available as enteric-coated capsules (100 mg, ~2.5 × 10^10 viable cells) for adults and children [1,2]. Germany and several EU countries approve Mutaflor as a medicinal product for ulcerative colitis remission maintenance and IBS-C [1]. Synlogic (Cambridge, MA, USA) develops engineered EcN derivatives (SYNB1891, SYNB1618). These are in clinical trials. They are not commercially available [5].