Background and methods: The immunomodulatory activity of a synbiotic combination containing three bacterial strains (Lactobacillus helveticus R0052, Bifidobacterium longum subsp. infantis R0033 and Bifidobacterium bifidum R0071) and short-chain fructooligosaccharide was examined in two distinct infectious rat models. In the T_h1 model, Wistar rats were administered the synbiotic combination for 2 weeks prior to challenge with a single oral dose of enterotoxigenic Escherichia coli or vehicle. In the T_h2 model, pretreated rats were challenged with a single subcutaneous dose of hook worm, Nippostrongylus brasiliensis. Blood samples were collected 3 hours or 4 days postchallenge and serum levels of pro- and anti-inflammatory cytokines were measured. Results: Significant reductions in pro-inflammatory cytokines interleukin (IL)-1α, IL-1β, IL-6, and tumour necrosis factor (TNF)-α were observed in both models suggesting a single, unifying mode of action on an upstream regulator. The N. brasiliensis study also compared the effect of the individual strains to synbiotic. For most of cytokines the combination appeared to average the effect of the individual strains with the exception of IL-4 and IL-10 where there was apparent synergy for the combination. Furthermore, the cytokine response varied by strain. Conclusions: It was concluded that this synbiotic combination of these three microbes could be beneficial in both T_h1 and T_h2 diseases.