Probiotic in Irritable Bowel Syndrome (IBS) Patients With Diarrhea
Probiotic in Irritable Bowel Syndrome (IBS) Patients With Diarrhea
We present the study design of a clinical trial designed to assess the clinical effects of
 the multispecies probiotic combination "BIO-25" in IBS-D patients. To this aim the primary
 endpoints of the study will be improvement in abdominal pain and stool consistency. The study
 will also be designed and powered to investigate the effect of the probiotic BIO-25 on the
 putative inflammation-associated parameters related to microinflammation in IBS, using
 postulated improvements in Hs-CRP, and calprotectin as markers of that effect. Additional
 aims of the study will examine the possible effect of probiotic BIO-25 on the cholinergic
 status.
Probiotic treatment in IBS is safe and effective. Probiotics have been shown to improve the
 anti-inflammatory/proinflammatory ratio, and may also improve intestinal motility, and the
 bacterial composition of the intestines. There is a substantial body of evidence in support
 of the use of probiotics in IBS. Probiotics appear to be particularly effective in the
 reduction of abdominal bloating and discomfort. The strains of the multispecies probiotic
 combination (BIO-25 LR) were tested and found to be beneficial in well-designed studies of
 IBS patients. Patients with post-infectious IBS, as well as many patients with "classic" IBS,
 manifest a low-grade inflammatory state that may be associated with visceral hypersensitivity
 and impaired motility. Probiotics may suppress this low-grade inflammation. In a recent study
 we found that highly sensitive CRP (hs-CRP), a serum marker of micro-inflammation, was
 significantly higher in patients with diarrhea-predominant IBS than healthy controls,
 although within normal limits in both groups. Thus, hs-CRP may serve as a marker of this
 low-grade, sub-clinical inflammation. If treatment with probiotic reduces the degree of
 low-grade inflammation in IBS, the improvement may be reflected in reduced hs-CRP levels.
 This study can contribute to our understanding of the pathophysiology of IBS and provide
 further evidence for the effectiveness of probiotic in its treatment.
Inclusion Criteria:

 A diagnosis of IBS-D according to the Rome III criteria, agreement to participate and the
 ability to sign an informed consent. Moreover, the definition of inclusion criteria is
 based on the FDA Draft Guidance for Clinical Evaluation of Products (add ref here). Over
 the two week run-in period:

 -  Pain Intensity: weekly average of worst abdominal pain in past 24 hours score of ≥ 3.0
 on a 0 (no pain at all) to 10 (worst possible pain) point scale

 -  Stool Consistency: ≥30% of days/week with at least one stool ≥6 using the Bristol
 Stool Score (BSS, Fig. 1) (ref).

 Exclusion Criteria:

 1) Hyperthyroidism, 2) celiac disease 3) pregnancy, 4) other gastrointestinal diagnoses
 that might interfere with the study (e.g. active peptic disease, inflammatory bowel
 disease), 5) a history of malignancy that might, to the best judgment of the doctor,
 interfere with the study, 6) any infectious or inflammatory disease within the last month,
 7) active medically treated asthma, 8) baseline levels of HsCRP > 10mg/liter, 9) steroid
 treatment for any indication, 10) fecal incontinence, and 11) treatment with probiotics or
 antibiotics of any kind within the last 4 weeks, 11) Diabetes.