Dataset Information

Oral Administration of the Probiotic Strain Escherichia coli Nissle 1917 Reduces Susceptibility to Neuroinflammation and Repairs Experimental Autoimmune Encephalomyelitis-Induced Intestinal Barrier Dysfunction.

ABSTRACT: Multiple sclerosis (MS) is a chronic inflammatory disease of the central nervous system (CNS) with an increasing incidence in developed countries. Recent reports suggest that modulation of the gut microbiota might be one promising therapy for MS. Here, we investigated whether the probiotic Escherichia coli strain Nissle 1917 (ECN) could modulate the outcome of experimental autoimmune encephalomyelitis (EAE), a murine model of MS. We evidenced that daily oral treatment with ECN, but not with the archetypal K12 E. coli strain MG1655, reduced the severity of EAE induced by immunization with the MOG_35-55 peptide. This beneficial effect was associated with a decreased secretion of inflammatory cytokines and an increased production of the anti-inflammatory cytokine IL-10 by autoreactive CD4 T cells, both in peripheral lymph nodes and CNS. Interestingly, ECN-treated mice exhibited increased numbers of MOG-specific CD4⁺ T cells in the periphery contrasting with severely reduced numbers in the CNS, suggesting that ECN might affect T cell migration from the periphery to the CNS through a modulation of their activation and/or differentiation. In addition, we demonstrated that EAE is associated with a profound defect in the intestinal barrier function and that treatment with ECN, but not with MG1655, repaired intestinal permeability dysfunction. Collectively, our data reveal that EAE induces a disruption of the intestinal homeostasis and that ECN protects from disease and restores the intestinal barrier function.

SUBMITTER: Secher T

PROVIDER: S-EPMC5603654 | biostudies-literature | 2017

REPOSITORIES: biostudies-literature

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Publications

Oral Administration of the Probiotic Strain <i>Escherichia coli</i> Nissle 1917 Reduces Susceptibility to Neuroinflammation and Repairs Experimental Autoimmune Encephalomyelitis-Induced Intestinal Barrier Dysfunction.

Secher Thomas T Kassem Sahar S Benamar Mehdi M Bernard Isabelle I Boury Michele M Barreau Frederick F Oswald Eric E Saoudi Abdelhadi A

Frontiers in immunology 20170914

Multiple sclerosis (MS) is a chronic inflammatory disease of the central nervous system (CNS) with an increasing incidence in developed countries. Recent reports suggest that modulation of the gut microbiota might be one promising therapy for MS. Here, we investigated whether the probiotic <i>Escherichia coli</i> strain Nissle 1917 (ECN) could modulate the outcome of experimental autoimmune encephalomyelitis (EAE), a murine model of MS. We evidenced that daily oral treatment with ECN, but not wi ...[more]

PMID: 28959254

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Project description:Although Escherichia coli Nissle 1917 (EcN) has been used therapeutically for over a century, the determinants of its probiotic properties remain elusive. EcN produces two siderophore-microcins (Mcc) responsible for an antagonistic activity against other Enterobacteriaceae. EcN also synthesizes the genotoxin colibactin encoded by the pks island. Colibactin is a virulence factor and a putative pro-carcinogenic compound. Therefore, we aimed to decouple the antagonistic activity of EcN from its genotoxic activity. We demonstrated that the pks-encoded ClbP, the peptidase that activates colibactin, is required for the antagonistic activity of EcN. The analysis of a series of ClbP mutants revealed that this activity is linked to the transmembrane helices of ClbP and not the periplasmic peptidase domain, indicating the transmembrane domain is involved in some aspect of Mcc biosynthesis or secretion. A single amino acid substitution in ClbP inactivates the genotoxic activity but maintains the antagonistic activity. In an in vivo salmonellosis model, this point mutant reduced the clinical signs and the fecal shedding of Salmonella similarly to the wild type strain, whereas the clbP deletion mutant could neither protect nor outcompete the pathogen. The ClbP-dependent antibacterial effect was also observed in vitro with other E. coli strains that carry both a truncated form of the Mcc gene cluster and the pks island. In such strains, siderophore-Mcc synthesis also required the glucosyltransferase IroB involved in salmochelin production. This interplay between colibactin, salmochelin, and siderophore-Mcc biosynthetic pathways suggests that these genomic islands were co-selected and played a role in the evolution of E. coli from phylogroup B2. This co-evolution observed in EcN illustrates the fine margin between pathogenicity and probiotic activity, and the need to address both the effectiveness and safety of probiotics. Decoupling the antagonistic from the genotoxic activity by specifically inactivating ClbP peptidase domain opens the way to the safe use of EcN.

Dataset Information

Oral Administration of the Probiotic Strain Escherichia coli Nissle 1917 Reduces Susceptibility to Neuroinflammation and Repairs Experimental Autoimmune Encephalomyelitis-Induced Intestinal Barrier Dysfunction.

Publications

Oral Administration of the Probiotic Strain <i>Escherichia coli</i> Nissle 1917 Reduces Susceptibility to Neuroinflammation and Repairs Experimental Autoimmune Encephalomyelitis-Induced Intestinal Barrier Dysfunction.

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