The proposed pilot project for this seed grant focuses on the role of intestinal serine-proteases in the pathogenesis of diarrhea-predominant IBS (D-IBS). In this study we will further assess serine-protease activity in patients with D-IBS and also explore a possible mechanism by which these proteases can lead to alterations in intestinal physiology and symptoms in these patients.

The general hypotheses for the proposed research are that (A) the levels of fecal serine-protease in patients with D-IBS are abnormally increased (B) this abnormal serine-protease activity leads to/is associated with an abnormal increase in intestinal permeability and therefore enables (C) chronic stimulation and activation of the mucosal immune system in these patients. In addition, it is aim to determine whither periodontal inflammation is associated with intestinal permeability and serine protease activity.

Inclusion Criteria:

• Any sex, race, or ethnicity.
• At least 18 years of age (no upper age limit).
• D-IBS patients must meet Rome III criteria for IBS and must have been evaluated by a physician to exclude other diseases that could explain the symptoms. For the latter, patients self statement is acceptable (no official document is required).
• Participation in Dr. Whitehead's 'heterogeneity of IBS' and/or Dr. Ringel's 'intestinal inflammation in patients with D-IBS' research study.

Exclusion Criteria:

• Healthy controls must have no significant or recurring gastrointestinal symptoms.
• Patients and healthy controls should not have a serious, unstable medical condition.
• Patients and healthy controls must have had no gastrointestinal tract surgery other than appendectomy or cholecystectomy.
• Patients and healthy controls must not be pregnant (by self-report). Pregnant women will not be allowed to participate as pregnancy can affect gastrointestinal symptoms.
• Patients and healthy controls must not have a history of inflammatory bowel disease, celiac disease, or other diagnosis that could explain chronic or recurring bowel symptoms in IBS patients or controls.
• Patients and healthy controls should have no history of lactose malabsorption (by self-report).
• Patients and healthy controls should have no history of clinical symptoms of acute infections during the last 8 weeks prior to enrolment in the study.
• Patients and healthy controls should have no history of anti-inflammatory agents including aspirin, non-aspirin, non-steroid anti-inflammatory (NSAID) or steroids in the last four weeks prior to study enrollment.
• Patients should not intentionally consume probiotics or undergo antibiotic treatment during the last 4 weeks prior to enrolment in the study. If the subject consumed any of these medications, a washout period of 4 weeks will be required).
• Patients must have no history of fainting or light headedness during periods of fasting.
• Patients must not have diabetes mellitus, or any similar conditions, that would cause an adverse reaction to the sugar drink.

Men and women of any race or ethnicity at least 18 years or older who have Diarrhea predominant Irritable Bowel Syndrome (D-IBS, n = 30) and healthy controls (n = 30).