title: Is the mucosal route of administration essential for probiotic function? Subcutaneous administration is associated with attenuation of murine colitis and arthritis.
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.
  
  
  OBJECTIVE
  (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 beta (TGF-beta) 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-beta.
authors.affiliation: Alimentary Pharmabiotic Centre, Department of Medicine, National University of Ireland, Cork, Ireland.
authors.forename: B
authors.initials: B
authors.lastname: Sheil
authors.forename: J
authors.initials: J
authors.lastname: McCarthy
authors.forename: L
authors.initials: L
authors.lastname: O'Mahony
authors.forename: M W
authors.initials: MW
authors.lastname: Bennett
authors.forename: P
authors.initials: P
authors.lastname: Ryan
authors.forename: J J
authors.initials: JJ
authors.lastname: Fitzgibbon
authors.forename: B
authors.initials: B
authors.lastname: Kiely
authors.forename: J K
authors.initials: JK
authors.lastname: Collins
authors.forename: F
authors.initials: F
authors.lastname: Shanahan
mesh_terms: D000818:Animals; D001169:Arthritis, Experimental / Q000473:pathology / Q000517:prevention & control*; D002478:Cells, Cultured; D003092:Colitis / Q000276:immunology / Q000473:pathology / Q000628:therapy*; D016207:Cytokines / Q000096:biosynthesis; D005260:Female; D007279:Injections, Subcutaneous; D007778:Lactobacillus; D051379:Mice; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D019936:Probiotics / Q000008:administration & dosage* / Q000627:therapeutic use; D011897:Random Allocation; D013154:Spleen / Q000276:immunology
chemical_list: D016207:Cytokines