Lay Summary

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 live organisms that can promote health.  Several large studies are underway to explore the potential usefulness of probiotics in different groups of patients with inflammatory bowel disease (IBD), both in Europe and in North America.

The exact ways in which probiotics may be working in terms of reducing pain and/or inflammation in inflammatory bowel disease are not known.  We have been able to show that colonization of the intestine of mice by a particular probiotic organism leads to significant behavioral change in a standard model of depression.  This indicates that intestinal flora can change a behavioral response in the brain.  Therefore, a distinct possibility exists that there is a nerve-mediated response to probiotic colonization of the intestine.  Thus, there is a rational basis for examining in more detail the extent to which probiotic colonization influences several different models of intestinal inflammation and whether this is contributed to or mediated by efferent neuronal pathways involving the vagus.  We will employ standard electrophysiological recording to identify whether probiotics affect the threshold for sensation of visceral pain and whether this is located in the enteric nerves or beyond the spinal cord.  We will also test if probiotics have any effect on the perception of somatic pain.  We will examine the role of the anti-inflammatory cholinergic receptor in these systems by using a transgenic model in which the receptor (a7) has been knocked out.  We will also examine whether nerve growth factor (NGF), an unusual molecule necessary for nerve growth and which has been described as having potent anti-inflammatory effects in many systems including a model of colitis, plays a role in the probiotic downregulation of inflammation.

The experiments outlined will explore the role of a probiotic organism on regulating inflammation and visceral pain or even somatic pain through interaction and utilization of certain pathways.  Furthermore, novel information about how probiotics may work in these models may be forthcoming.  This would provide evidence for the involvement of the nervous system in these conditions in man and offer totally new therapeutic targets for intervention.