E. coli Nissle

Microbiota-host communication is primarily achieved by secreted factors that can penetrate the mucosal surface, such as extracellular membrane vesicles (EVs). The EVs released by the gut microbiota have been extensively studied in cellular and experimental models of human diseases. However, little is known about their in vivo effects in early life, specifically regarding immune and intestinal maturation. This study aimed to investigate the effects of daily administration of EVs from probiotic and commensal E...

BACKGROUND & AIMS: Hereditary tyrosinemia type 1 (HT1) results from the loss of fumarylacetoacetate hydrolase (FAH) activity and can lead to lethal liver injury. Therapeutic options for HT1 remain limited. In this study, we aimed to construct an engineered bacterium capable of reprogramming host metabolism and thereby provide a potential alternative approach for the treatment of HT1. METHODS: Escherichia coli Nissle 1917 (EcN) was engineered to express genes involved in tyrosine metabolism in the anoxic conditions that are characteristic of the intestine (EcN-HT)...

Probiotic bacteria confer multiple health benefits, including preventing the growth, colonization, or carriage of harmful bacteria in the gut. Bacteriocins are antibacterial peptides produced by diverse bacteria, and their production is tightly regulated and coordinated at the transcriptional level. A popular strategy for enhancing the antibacterial properties of probiotic bacteria is to retrofit them with the ability to overproduce heterologous bacteriocins. This is often achieved from non-native constitutive promoters or in response to host or pathogen signal from synthetic promoters...

γ-Conglutin (γ-C) from lupin seeds has been identified as a potent allergen with cross reactivity to peanuts. Here, we investigated how γ-C affected the response in bone marrow-derived dendritic cells (DCs) to bacterial stimuli. γ-C enhanced L. acidophilus NCFM (LaNCFM)-induced IL-12, IL-10, and IL-23 dose-dependently. In contrast, together with E. coli Nissle or LPS, γ-C reduced the production of IL-12 but not of IL-23 and IL-10. Enzyme-hydrolyzed γ-C also enhanced LaNCFM-induced IL-12 and IL-23 production...

For patients with ulcerative colitis (UC), administration of the probiotic E. coli Nissle (EcN) holds promise for alleviation of disease symptoms. The mechanisms are unclear, but it has been hypothesised that a capacity of the probiotic to outcompete potentially detrimental UC-associated E. coli strains plays an important role. However, this could previously not be confirmed in a mouse model of competition between EcN and two UC-associated strains, as reported by Petersen et al. 2011. In the present study, we re-evaluated the idea, hypothesising that delivery of EcN by a micro device dosing system (microcontainers), designed for delivery into the intestinal mucus, could support colonisation and confer a competition advantage compared to classical oral dosing...

OBJECTIVE: Metabolic dysfunction-associated steatotic liver disease (MASLD), formerly known as non-alcoholic fatty liver disease (NAFLD), is the most prevalent liver disease globally, yet no therapies are approved. The effects of Escherichia coli Nissle 1917 expressing aldafermin, an engineered analog of the intestinal hormone FGF19, in combination with dietary change were investigated as a potential treatment for MASLD. METHODS: MASLD was induced in C57BL/6J male mice by American lifestyle-induced obesity syndrome diet and then switched to a standard chow diet for seven weeks...

UNLABELLED: Abstract. BACKGROUND: The development of proper immune responses to Newcastle disease (ND) vaccines is important in controlling the disease. Escherichia coli strain Nissle 1917 (EcN) is involved in regulating the immune system. AIMS: The current study evaluated the effects of EcN on immune responses to ND live vaccines in Japanese quails. METHODS: A total of 150 one-day-old quails were divided into three equal groups...

Considerable evidence suggests that insulin resistance is closely linked to Parkinson's disease (PD), leading to agents aiming at treating diabetes can be regarded as new neuroprotective strategies in PD, notably glucagon-like peptide-1 (GLP-1). However, the extremely short half-life of GLP-1 due to degradation by the ubiquitous proteolytic enzyme limits its clinical application. In this study, we engineered the recombinant integrant probiotic strain Escherichia coli Nissle 1917 (EcN) to create a strain EcN-GLP-1 that effectively delivers the heterologous GLP-1 molecule...

As a foodborne pathogen of global importance, Salmonella enterica serovar Enteritidis ( S. Enteritidis) is a threat to public health that is mainly spread by poultry products. Intestinal Enterobacteriaceae can inhibit the colonization of S. Enteritidis and are regarded as a potential antibiotic substitute. We investigated, in chicks, the anti- S. Enteritidis effects of Escherichia coli ( E. coli ) Nissle 1917, the most well-known probiotic member of Enterobacteriaceae. Eighty 1-d-old healthy female AA broilers were randomly divided into 4 groups, with 20 in each group, namely the negative control (group P), the E...

Chronic stress can lead to prolonged adrenal gland secretion of cortisol, resulting in human ailments such as anxiety, post-traumatic stress disorder, metabolic syndrome, diabetes, immunosuppression, and cardiomyopathy. Real time monitoring of chronic increases in cortisol and intervening therapies to minimize the physiological effects of stress would be beneficial to prevent these endocrine related illnesses. Gut microbiota have shown the ability to secrete, respond, and even regulate endocrine hormones. One such microbe, Clostridium scindens , responds transcriptionally to cortisol...

Synthetic biology provides a means of engineering tailored functions into probiotic bacteria. Of particular interest is introducing microbial sense and response functions; however, techniques for testing in physiologically relevant environments, such as those for the intended use, are still lacking. Typically, engineered probiotics are developed and tested in monoculture or in simplified cocultures still within ideal environments. In vitro fermentation models using simplified microbial communities now allow us to simulate engineered organism behavior, specifically organism persistence and intended functionality, within more physiologically relevant, tailored microbial communities...

In this study we performed a step-wise optimization of biologically active IL-2 for delivery using E. coli Nissle 1917. Engineering of the strain was coupled with an in vitro cell assay to measure the biological activity of microbially produced IL-2 (mi-IL2). Next, we assessed the immune modulatory potential of mi-IL2 using a 3D tumor spheroid model demonstrating a strong effect on immune cell activation. Finally, we evaluated the anticancer properties of the engineered strain in a murine CT26 tumor model. The engineered strain was injected intravenously and selectively colonized tumors...

Probiotics play an important role against infectious pathogens, such as Escherichia coli ( E. coli ), mainly through the production of antimicrobial compounds and their immunomodulatory effect. This protection can be detected both on the live probiotic microorganisms and in their inactive forms (paraprobiotics). Probiotics may affect different cells involved in immunity, such as macrophages. Macrophages are activated through contact with microorganisms or their products (lipopolysaccharides, endotoxins or cell walls)...

Widespread antibiotic resistance in commensal bacteria creates a persistent challenge for human health. Resident drug-resistant microbes can prevent clinical interventions, colonize wounds post-surgery, pass resistance traits to pathogens or move to more harmful niches following routine interventions such as catheterization. Accelerating the removal of resistant bacteria or actively decolonizing particular lineages from hosts could therefore have a number of long-term benefits. However, removing resident bacteria via competition with probiotics, for example, poses a number of ecological challenges...

OBJECTIVES: To investigate the probiotic Escherichia coli Nissle 1917 (EcN) in canine idiopathic diarrhea and urinary tract infections. ANIMALS/SAMPLES: The utility of EcN was explored in a 3-phase study from March 2017 to June 2020. Eighty-nine dogs with idiopathic diarrhea were included in phase 1, 3 healthy dogs were included in phase 2, and uropathogenic E coli (UPEC) isolates from 38 dogs with urinary tract infections were included in phase 3. PROCEDURES: In phase 1, dogs with diarrhea were prospectively enrolled in a randomized study to receive EcN (108 EcN bacteria/mL; < 10 kg received 5 mL/dose, 10 to 25 kg received 10 mL/dose, or > 25 kg received 15 mL/dose) or placebo for 3 days, followed by a 15-day observation phase...

To build therapeutic strains, Escherichia coli Nissle (EcN) have been engineered to express antibiotics, toxin-degrading enzymes, immunoregulators, and anti-cancer chemotherapies. For efficacy, the recombinant genes need to be highly expressed, but this imposes a burden on the cell, and plasmids are difficult to maintain in the body. To address these problems, we have developed landing pads in the EcN genome and genetic circuits to control therapeutic gene expression. These tools were applied to EcN SYNB1618, undergoing clinical trials as a phenylketonuria treatment...

Genetically engineered microbes, especially Escherichia coli, have been widely used in the biosynthesis of proteins and metabolites for medical and industrial applications. As a traditional probiotic with a well-established safety record, E. coli Nissle 1917 (EcN) has recently emerged as a microbial chassis for generating living therapeutics, drug delivery vehicles, and microbial platforms for industrial production. Despite the availability of genetic tools for engineering laboratory E. coli K-12 and B strains, new genetic engineering systems are still greatly needed to expand the application range of EcN...

Engineered microorganisms such as the probiotic strain Escherichia coli Nissle 1917 (EcN) offer a strategy to sense and modulate the concentration of metabolites or therapeutics in the gastrointestinal tract. Here, we present an approach to regulate production of the depression-associated metabolite gamma-aminobutyric acid (GABA) in EcN using genetic circuits that implement negative feedback. We engineered EcN to produce GABA by overexpressing glutamate decarboxylase (GadB) from E. coli and applied an intracellular GABA biosensor to identify growth conditions that improve GABA biosynthesis...

OBJECTIVE: Gut microbiota and its metabolites have regulatory effects on PCOS related ovarian dysfunction and insulin resistance. Escherichia coli Nissle 1917 (EcN) is a genetically controlled probiotic with an excellent human safety record for improving gut microbiome metabolic disorders and immune system disorders. Here we focused to explore the application and effect of probiotic EcN on the gut microbiota-metabolism-IL-22-mitochondrial damage axis in PCOS. METHODS: PCOS mice were constructed with dehydroepiandrosterone (DHEA) and treated with EcN, FMT or IL-22 inhibitors...

PURPOSE: SYNB1891 is a live, modified strain of the probiotic Escherichia coli Nissle 1917 (EcN) engineered to produce cyclic dinucleotides under hypoxia, leading to STimulator of INterferon Genes (STING) activation in phagocytic antigen-presenting cells in tumors and activating complementary innate immune pathways. PATIENTS AND METHODS: This first-in-human study (NCT04167137) enrolled participants with refractory advanced cancers to receive repeat intratumoral injections of SYNB1891 either alone or in combination with atezolizumab, with the primary objective of evaluating the safety and tolerability of both regimens...