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Is the mucosal route of administration essential for probiotic function? Subcutaneous administration is associated with attenuation of murine colitis and arthritis
  1. B Sheil1,
  2. J McCarthy1,
  3. L O’Mahony1,
  4. M W Bennett2,
  5. P Ryan2,
  6. J J Fitzgibbon2,
  7. B Kiely3,
  8. J K Collins4,
  9. F Shanahan1
  1. 1Alimentary Pharmabiotic Centre, Department of Medicine, National University of Ireland, Cork, Ireland
  2. 2Alimentary Pharmabiotic Centre, Departments of Pathology, National University of Ireland, Cork, Ireland
  3. 3Alimentary Pharmabiotic Centre, Department of Microbiology, National University of Ireland, Cork, Ireland
  4. 4Alimentary Pharmabiotic Centre, Departments of Medicine and Microbiology, National University of Ireland, Cork, Ireland
  1. Correspondence to:
    Professor F Shanahan
    Alimentary Pharmabiotic Centre, Department of Medicine, National University of Ireland, Cork, Ireland; f.shanahanucc.ie

Abstract

Background: We and others have reported the prophylactic efficacy of oral consumption of probiotic lactobacilli in the interleukin 10 knockout (IL-10 KO) model of colitis. It has not been demonstrated that the oral route is essential for probiotic efficacy.

Aims: (i) To determine the effect of parenteral administration (subcutaneous) of Lactobacillus salivarius 118 on colitis of IL-10 KO mice; and (ii) to determine if observed responses are disease specific.

Methods: (i) IL-10 KO mice were injected subcutaneously with L salivarius 118 or saline over 19 weeks. At sacrifice, the bowels were histologically scored. Isolated splenocytes were cultured in vitro and cytokine levels measured. (ii) In the collagen induced arthritis model, DBA/1 mice were injected subcutaneously with the probiotic or saline. At sacrifice, paw thickness was measured and joints were histologically scored.

Results: (i) Colonic inflammatory scores were significantly decreased in IL-10 KO mice injected with L salivarius 118 compared with controls (p<0.05). Proinflammatory cytokine production from stimulated splenocytes was significantly lower for the probiotic group whereas stimulated transforming growth factor β (TGF-β) levels were significantly increased (p<0.05). (ii) Scoring of arthritis and paw thickness were significantly improved in the group of mice injected with L salivarius 118 compared with controls.

Conclusions: (1) Subcutaneous administration of L salivarius 118 significantly attenuated colitis in the IL-10 KO model and suppressed collagen induced arthritis, suggesting that the oral route may not be essential for probiotic anti-inflammatory effects and that responses are not disease specific. (2) The probiotic effect was associated with reduced production of proinflammatory (T helper 1) cytokines and maintained production of anti-TGF-β.

  • colitis
  • probiotics
  • arthritis
  • cytokines
  • IL-10 KO, interleukin 10 knockout
  • PBS, phosphate buffered saline
  • MRS broth, Man, Rogosa, Sharpe broth
  • DMEM, Dulbecco’s modified Eagle’s medium
  • TNF-α, tumour necrosis factor α
  • IL-12, interleukin 12
  • TGF-β, transforming growth factor β
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Footnotes

  • Conflict of interest: LO’M, BK, JKC, and FS are members of a multidepartmental university campus research company (Alimentary Health Ltd) which investigates host-flora interactions and the therapeutic manipulation of these interactions in various human and animal diseases. The content of this article was neither affected nor constrained by this fact.

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