Effects in the use of a genetically engineered strain of Lactococcus lactis delivering in situ IL-10 as a therapy to treat low-grade colon inflammation.

Abstract : : Irritable bowel syndrome (IBS) is a gastrointestinal disorder characterized by chronic abdominal pain, discomfort, and bloating. Interestingly, there is now evidence of the presence of a low grade inflammation status in many IBS patients, including histopathological and mucosal cytokine levels in the colon, as well as the presence of IBS-like symptoms in quiescent inflammatory bowel disease (IBD). The use of a genetically engineered food-grade bacterium, such as Lactococcus lactis, secreting the anti-inflammatory cytokine IL-10 has been proven by many pre-clinical studies to be a successful therapy to treat colon inflammation. In this study, we first reproduced the recovery-recurrence periods observed in IBS-patients in a new chronic model characterized by two episodes of DiNitro-BenzeneSulfonic-acid (DNBS)-challenge and we tested the effects of a recombinant strain of L. lactis secreting IL-10 under a Stress-Inducible Controlled Expression (SICE) system. In vivo gut permeability, colonic serotonin levels, cytokine profiles and spleen cell populations were then measured as readouts of a low-grade inflammation. In addition, since there is increasing evidence that gut microbiota tightly regulates gut barrier function, tight junction proteins were also measured by qRT-PCR after administration of recombinant L. lactis in DNBS-treated mice. Strikingly, oral administration of L. lactis secreting active IL-10 in mice resulted in significant protective effects in terms of permeability, immune activation and gut-function parameters. Although genetically engineered bacteria are, for now, used only as a "proof of concept," our study validates the interest in the use of the novel SICE system in L. lactis to express therapeutic molecule, such as IL-10, locally at mucosal surfaces.
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Submitted on : Wednesday, April 16, 2014 - 10:03:57 AM
Last modification on : Tuesday, February 26, 2019 - 10:12:45 AM

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Rebeca Martín, Florian Chain, Sylvie Miquel, Jane M Natividad, Harry Sokol, et al.. Effects in the use of a genetically engineered strain of Lactococcus lactis delivering in situ IL-10 as a therapy to treat low-grade colon inflammation.. Hum Vaccin Immunother, 2014, 10 (6), pp.1611-1621. ⟨10.4161/hv.28549⟩. ⟨hal-00979468⟩

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