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Hum Vaccin Immunother. 2014;10(6):1611-21. doi: 10.4161/hv.28549. Epub 2014 Apr 14.

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.

Author information

1
INRA; Commensal and Probiotics-Host Interactions Laboratory; UMR 1319 Micalis; Jouy-en-Josas, France; AgroParisTech; UMR1319 Micalis; Jouy-en-Josas, France.
2
Farncombe Family Digestive Health Research Institute; McMaster University; Hamilton, ON Canada.
3
INRA; Commensal and Probiotics-Host Interactions Laboratory; UMR 1319 Micalis; Jouy-en-Josas, France; AgroParisTech; UMR1319 Micalis; Jouy-en-Josas, France; Department of Gastroenterology and Nutrition; AP-HP; Hôpital Saint-Antoine F-75012 and UPMC Univ Paris; Paris, France; INSERM; Equipe AVENIR U1057 / UMR CNRS 7203; Paris, France.

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 inflammatory 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 2 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 molecules, such as IL-10, locally at mucosal surfaces.

KEYWORDS:

IBS; IL-10; Lactococcis lactis; genetically engineered bacteria; gut hyperpermeability; probiotic

PMID:
24732667
PMCID:
PMC5396252
DOI:
10.4161/hv.28549
[Indexed for MEDLINE]
Free PMC Article

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