Abstract
Escherichia coli Nissle 1917 (EcN) is a probiotic strain with proven efficacy in inducing and maintaining remission of ulcerative colitis. However, the microbial factors that mediate these beneficial effects are not fully known. Gram-negative bacteria release outer membrane vesicles (OMVs) as a direct pathway for delivering selected bacterial proteins and active compounds to the host. In fact, vesicles released by gut microbiota are emerging as key players in signaling processes in the intestinal mucosa. In the present study, the dextran sodium sulfate (DSS)-induced colitis mouse model was used to investigate the potential of EcN OMVs to ameliorate mucosal injury and inflammation in the gut. The experimental protocol involved pre-treatment with OMVs for 10 days before DSS intake, and a 5-day recovery period. Oral administration of purified EcN OMVs (5 μg/day) significantly reduced DSS-induced weight loss and ameliorated clinical symptoms and histological scores. OMVs treatment counteracted altered expression of cytokines and markers of intestinal barrier function. This study shows for the first time that EcN OMVs can mediate the anti-inflammatory and barrier protection effects previously reported for this probiotic in experimental colitis. Remarkably, translation of probiotics to human healthcare requires knowledge of the molecular mechanisms involved in probiotic–host interactions. Thus, OMVs, as a non-replicative bacterial form, could be explored as a new probiotic-derived therapeutic approach, with even lower risk of adverse events than probiotic administration.
Highlights
The term inflammatory bowel diseases (IBD) mainly refers to ulcerative colitis (UC) and Crohn’s disease
When dextran sodium sulfate (DSS) was orally administered to mice, the intestinal inflammatory status was induced, and characterized in the control colitic group (DSS control) by marked body weight loss (Figure 3A) and diarrhea with bleeding feces, which resulted in an increased disease activity index (DAI) score in this group from day 5 (Figure 3B)
Colon length is inversely associated with the severity of DSS-induced colitis (Pandurangan et al, 2015), and the colonic weight/length ratio is widely used as an indicator of the colonic oedema that typically occurs in experimental colitis (Hou et al, 2014)
Summary
The term IBD mainly refers to UC and Crohn’s disease. These are chronic inflammatory disorders of the intestinal tract that may cause life-threatening complications and have an increasing incidence worldwide. Many studies have evaluated the therapeutic potential of certain bacteria, including commensal and probiotic strains, to ameliorate IBD in clinical trials (Fedorak, 2010; Wasilewski et al, 2015) or in animal models of colitis (Ewaschuk et al, 2008; Garrido-Mesa et al, 2011; Shen et al, 2012; Kang et al, 2013; Martín et al, 2015; Souza et al, 2016) Overall, these studies have shown the ability of these bacteria to exert beneficial effects on parameters related with gut function, including improvement of gut permeability, reduction of inflammatory cytokine production and/or release, and amelioration of the histological alterations observed in these inflammatory conditions. These effects may be mediated, at least in part, by bacterial secreted factors (Ewaschuk et al, 2008; Martín et al, 2015) or by released membrane vesicles (Shen et al, 2012; Kang et al, 2013)
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