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. 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 b (TGF-b) 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-b.

RETRACTED ARTICLE: Improvement in Th1/Th2 immune homeostasis, antioxidative status and resistance to pathogenic E. coli on consumption of probiotic Lactobacillus rhamnosus fermented milk in aging mice

“…It has been shown that probiotics are capable of inhibiting the nuclear factor-kB pathway in epithelial cells through various mechanisms, including blocking inhibitor kB degradation by inhibiting ubiquination (Neish et al 2000) or by inhibiting proteasome function (Jijon et al 2004). Induction of Treg cells by certain probiotic bacterial strains has also been hypothesized to exert potent antiinflammatory effects (Sheil et al 2004). In contrast, during E. coli infection experiment, all measured inflammatory proteins recorded a remarkable increase in LR-fed group as compared to control group.…”

Diversity of the genus Lactobacillus revealed by comparative genomics of five species

“…This strain was isolated from the terminal ileum of a healthy human subject undergoing reconstructive urinary tract surgery (Dunne et al, 1999). It has been extensively studied for its probiotic properties in human trials and animal models (Dunne et al, 1999(Dunne et al, , 2001McCarthy et al, 2003;Sheil et al, 2004). Members of this species are commonly isolated from the oral and GI tracts of humans and other animals (Ahrne et al, 1998;Heilig et al, 2002;Molin et al, 1993;Rogosa et al, 1953).…”

Multireplicon genome architecture of Lactobacillus salivarius

“…salivarius strain UCC118 was isolated from the terminal ileum of a (otherwise healthy) patient undergoing urinary tract reconstructive surgery (8). This strain has been extensively studied for its probiotic properties in human trials and animal models (8)(9)(10)(11). In addition, L. salivarius UCC118 produces a two-component bacteriocin Abp118 (12), which has broad spectrum activity against Gram-positive bacteria, including methicillin-resistant Staphylococcus aureus (8).…”