The vagus nerve is an important pathway signalling immune activation of the G.I. tract to the brain. Probiotics are live organisms that may engage signaling pathways of the brain-gut axis to modulate inflammation. The protective effects of Lactobacillus reuteri (LR) and Bifidobacterium infantis (BI) during intestinal inflammation were studied after bdiaphragmatic vagotomy in acute DSS colitis in BALB/c mice and chronic colitis induced by transfer of CD4⁺ CD62L⁺ T lymphocytes from BALB/c into SCID mice. LR and BI (1x10⁹) were given daily. Clinical score, MPO levels, in vivo and in vitro secreted inflammatory cytokine levels were found to be more severe in mice that were vagotomized compared to sham-operated animals. LR in the acute DSS model was effective in decreasing the MPO and cytokine levels in the tissue in sham as well as vagotomized mice. BI had a strong downregulatory effect on secreted in vitro cytokine levels and had a greater anti-inflammatory effect in vagotomized- compared to sham-operated mice. Both LR and BI retained anti-inflammatory effects in vagotomized mice. In SCID mice vagotomy did not enhance inflammation, but BI was more effective in vagotomized mice than shams. Taken together, the intact vagus has a protective role in acute DSS-induced colitis in mice but not in the chronic T cell transfer model of colitis model. Furthermore, LR and BI do not seem to engage their protective effects via this cholinergic anti-inflammatory pathway but the results interestingly show that in the T cell transfer model vagotomy had a biologic effect as it increased the effectiveness of the BI in downregulation of colonic inflammation.