Scientific Abstract

Proposal No.  IBD-0109R
Principal Investigator:  John Bienenstock, M.D.
Applicant Organization:  McMaster University (Hamilton, Ontario, Canada)
Project Title: Is there a neurophysiologic basis for immunoregulation by probiotics?
Period of Award:  September 1, 2004 - August 31, 2007

Probiotics are nonpathogenic live organisms that promote health when ingested.  There is evidence to support a therapeutic role for probiotics in the treatment of inflammatory bowel disease.  In animal models of intestinal inflammation, treatment with probiotics leads to a marked reduction in disease severity.  While the anti-inflammatory mechanism of probiotics is unknown, recent studies have suggested that the probiotic attenuation of colitis in IL-10 deficient mice is associated with a reduced ability to produce Th1-type cytokines both mucosal and systemically.

There is constant communication between the intestine and the brain that occurs primarily through the vagus nerves.  We have evidence to suggest that probiotic organisms may engage signaling pathways of this brain-gut axis as mice colonized with (Lactobacillus) LB exhibit significantly lower levels of behavioral despair than sham-treated animals in the forced swim model of depression.  Communication between brain and gut is bi-directional and stimulation of the afferent or efferent vagus can lead to subsequent efferent activity and the release of acetylcholine. 

Our hypothesis is that colonization with a probiotic organism (Lactobacillus reuteri) leads to activation of a cholinergic anti-inflammatory pathway and vagally mediated antinociception that provide protection against the deleterious tissue damage and visceral hypersensitivity associated with IBD.

We will determine:

1.   If LB and/or NGF can mimic the effect of vagal stimulation on the endotoxin response.  We will examine the effect of probiotic ingestion and exogenous NGF on TNFα levels in the serum and GI tract of mice following LPS exposure. 

2.   If the cholinergic anti-inflammatory pathway is involved in the protective effects of LB in intestinal inflammation.

3.   The impact of treatment with the probiotic on the magnitude of visceral afferent and pseudoaffective responses to noxious colonic distension.  We will also examine whether the antinociceptive effects of LB include somatic pain.