Escherichia coli strain Nissle 1917 ameliorates experimental colitis by modulating intestinal permeability, the inflammatory response and clinical signs in a faecal transplantation model

Abstract

Inflammatory bowel diseases (IBDs) are a group of inflammatory conditions of the gut that include ulcerative colitis and Crohn's disease. Probiotics are live micro-organisms that may be used as adjuvant therapy for patients with IBD. The aim of this study was to evaluate the effect of prophylactic ingestion of Escherichia coli strain Nissle 1917 (EcN) in a murine model of colitis. For induction of colitis, mice were given a 3.5 % dextran sodium sulfate (DSS) solution for 7 days in drinking water. EcN administration to mice subjected to DSS-induced colitis resulted in significant reduction in clinical and histopathological signs of disease and preservation of intestinal permeability. We observed reduced inflammation, as assessed by reduced levels of neutrophils, eosinophils, chemokines and cytokines. We observed an increase in the number of regulatory T-cells in Peyer's patches. Germ-free mice received faecal content from control or EcN-treated mice and were then subjected to DSS-induced colitis. We observed protection from colitis in animals that were colonized with faecal content from EcNtreated mice. These results suggest that preventative oral administration of EcN or faecal microbiota transplantation with EcN-containing microbiota ameliorates DSS-induced colitis by modifying inflammatory responsiveness to DSS.

Commensal Escherichia coli Strains Can Promote Intestinal Inflammation via Differential Interleukin-6 Production

“…Further supporting the idea that the pathobiont phenotype may arise on multiple occasions are findings from others who report both context-dependent and strain-specific differences in the ability of E. coli isolates to either protect against or cause disease. Oral administration of the putative probiotic E. coli Nissle 1917 is documented to be protective during DSS-induced colitis ( 40 , 41 ). However, Nissle 1917 and E. coli K12 (a lab-adapted strain) both exacerbated intestinal inflammation and translocated to systemic organs in gnotobiotic C57BL/6j mice infected with Toxoplasma gondii ( 42 ).…”

Outer Membrane Vesicles and Soluble Factors Released by Probiotic Escherichia coli Nissle 1917 and Commensal ECOR63 Enhance Barrier Function by Regulating Expression of Tight Junction Proteins in Intestinal Epithelial Cells

“…Its therapeutic efficacy in the remission of ulcerative colitis has been proved through clinical trials (Kruis et al, 2004; reviewed by Scaldaferri et al, 2016). In addition, the effectiveness of this probiotic in the amelioration of induced experimental colitis in mice is well-documented (Grabig et al, 2006; Ukena et al, 2007; Garrido-Mesa et al, 2011; Olier et al, 2012; Souza et al, 2016). The ability of EcN to decrease intestinal permeability and cure leaky gut may be attributed, at least in part, to its ability to strength TJ.…”

“…Alterations in microbiota composition or aberrant responses to luminal bacteria or dietary components can result in increased intestinal permeability, which may lead to the development of such pathologies. In this context, many studies have been conducted to investigate the therapeutic potential of certain commensal and probiotic strains to ameliorate inflammatory bowel diseases in clinical trials (reviewed by Chibbar and Dieleman, 2015; Wasilewski et al, 2015) or in animal models of colitis (Ewaschuk et al, 2008; Arribas et al, 2009; Shen et al, 2012; Kang et al, 2013; Martin et al, 2014; Souza et al, 2016). In mice colitis models, beneficial bacteria reduce inflammatory cytokines, normalize gut permeability, and reinforce the epithelial barrier.…”

Fecal Microbiota Transplantation for Ulcerative Colitis: FoMenTing Change?

“…The treatment of IBD consists of immunomodulatory therapy that at times is supplemented by surgical interventions aiming to ensure longer remission periods and to prevent possible complications. Since dysbiosis, defined as an alteration of gut microbial species thought to be pathologic, is thought to contribute to IBD pathogenesis [6], the use of probiotics or FMT has been proposed as alternative therapies [7]. Although the efficacy of FMT has yet to be unambiguously supported in UC on the basis of very few randomized trials [8], the use of animal models to better understand the mechanism underlying this new approach is now being explored.…”

“…With regard to the use of probiotics or FMT to treat UC in a murine model [7,10,11], FMT is a more efficient therapy [9], perhaps related to the quantity and quality of bacteria, since FMT involves the entire fecal microbiota, whereas probiotic treatment introduces only a single or a few bacterial strains. The microbiota of healthy donors may act as a ''broad-spectrum antibiotic'' against pathogens with an added benefit of adding needed bacterial species, normalizing the overall microbial composition.…”