Probiotic Bifidobacterium longum NCC3001 Reduces Depression Scores and Alters Brain Activity: A Pilot Study in Patients With Irritable Bowel Syndrome.

BACKGROUND & AIMS: Probiotics can reduce symptoms of irritable bowel syndrome (IBS), but little is known about their effects on psychiatric comorbidities. We performed a prospective study to evaluate the effects of Bifidobacterium longum NCC3001 (BL) on anxiety and depression in patients with IBS. METHODS: We performed a randomized, double-blind, placebo-controlled study of 44 adults with IBS and diarrhea or a mixed-stool pattern (based on Rome III criteria) and mild to moderate anxiety and/or depression (based on the Hospital Anxiety and Depression scale) at McMaster University in Canada, from March 2011 to May 2014. At the screening visit, clinical history and symptoms were assessed and blood samples were collected. Patients were then randomly assigned to groups and given daily BL (n = 22) or placebo (n = 22) for 6 weeks. At weeks 0, 6, and 10, we determined patients' levels of anxiety and depression, IBS symptoms, quality of life, and somatization using validated questionnaires. At weeks 0 and 6, stool, urine and blood samples were collected, and functional magnetic resonance imaging (fMRI) test was performed. We assessed brain activation patterns, fecal microbiota, urine metabolome profiles, serum markers of inflammation, neurotransmitters, and neurotrophin levels. RESULTS: At week 6, 14 of 22 patients in the BL group had reduction in depression scores of 2 points or more on the Hospital Anxiety and Depression scale, vs 7 of 22 patients in the placebo group (P = .04). BL had no significant effect on anxiety or IBS symptoms. Patients in the BL group had a mean increase in quality of life score compared with the placebo group. The fMRI analysis showed that BL reduced responses to negative emotional stimuli in multiple brain areas, including amygdala and fronto-limbic regions, compared with placebo. The groups had similar fecal microbiota profiles, serum markers of inflammation, and levels of neurotrophins and neurotransmitters, but the BL group had reduced urine levels of methylamines and aromatic amino acids metabolites. At week 10, depression scores were reduced in patients given BL vs placebo. CONCLUSION: In a placebo-controlled trial, we found that the probiotic BL reduces depression but not anxiety scores and increases quality of life in patients with IBS. These improvements were associated with changes in brain activation patterns that indicate that this probiotic reduces limbic reactivity. ClinicalTrials.gov no. NCT01276626.

Lack of utility of symptoms and signs at first presentation as predictors of inflammatory bowel disease in secondary care.

OBJECTIVES: There are few data concerning the utility of symptoms and signs at first presentation in predicting a diagnosis of ulcerative colitis (UC) or Crohn's disease (CD). We conducted a study to examine this issue in secondary care. METHODS: We collected complete symptom, colonoscopy, and histology data prospectively from 1,981 consecutive adult patients with lower gastrointestinal symptoms at two hospitals in Hamilton, Ontario. Assessors were blinded to symptom status. The reference standard used to define the presence of UC or CD was according to accepted histological criteria. Patients without UC or CD served as controls. Sensitivity, specificity, and positive and negative likelihood ratios (LRs) were calculated for individual items from the clinical history, as well as combinations of these. RESULTS: In identifying 302 patients with inflammatory bowel diseases (IBD), positive LRs for individual items ranged from 1.18 (incomplete emptying) to 2.30 (passage of stools more than four times per day at least most of the time) and negative LRs from 0.70 (bloody stools) to 0.96 (incomplete emptying). Combinations of items had a high specificity, but at the expense of sensitivity. Items that were independent predictors of IBD after logistic regression analysis were family history of IBD, younger age, passage of stools more than four times per day ≥75% of the time, urgency most of the time, and anemia. CONCLUSIONS: Individual items from the clinical history are not helpful in predicting a diagnosis of UC or CD. However, this may be because some items lacked sufficient detail. Combinations of symptoms and computer models had a high specificity, but overall were only modestly useful diagnostically. Future studies should evaluate biological markers in combination with symptoms to improve accuracy.

Prevalence of organic disease at colonoscopy in patients with symptoms compatible with irritable bowel syndrome: cross-sectional survey.

OBJECTIVE: Guidelines for the management of irritable bowel syndrome (IBS) encourage a positive diagnosis, but some evidence suggests organic disease may be missed unless investigations are performed. We examined yield of colonoscopy in a cohort of secondary care patients meeting criteria for IBS. MATERIALS AND METHODS: Demographic data, symptoms and findings at colonoscopy were recorded prospectively in consecutive, unselected adults with gastrointestinal (GI) symptoms compatible with IBS according to the Rome III criteria. Prevalence of organic GI disease was compared between those meeting criteria for IBS, according to the presence or absence of co-existent alarm features, and by IBS subtype. RESULTS: A total of 559 patients met Rome III criteria for IBS, of whom 423 reported ≥1 alarm feature and 136 none. There was a significantly higher prevalence of organic GI disease among those reporting alarm features (117 [27.7%]), compared with those without (21 [15.4%]) (p = 0.002). In the latter group of 136 patients, Crohn's disease was the commonest finding (10 [7.4%] subjects), followed by coeliac disease (4 [2.9%] subjects), and microscopic colitis (3 [2.2%] subjects). Regardless of presence or absence of alarm features, patients with constipation-predominant IBS were less likely to exhibit organic GI disease than those with diarrhea-predominant or mixed IBS (12.7% vs. 32.1% and 23.8%, p = 0.006). CONCLUSIONS: One in six patients with symptoms compatible with IBS without alarm features in this selected group exhibited organic GI disease following investigation. Assessment of alarm features in a comprehensive history is vital to reduce diagnostic uncertainty that can surround IBS.

The Rome III criteria for the diagnosis of functional dyspepsia in secondary care are not superior to previous definitions.

BACKGROUND & AIMS: Although the Rome III criteria for functional dyspepsia were defined 7 years ago, they have yet to be validated in a rigorous study. We addressed this issue in a secondary-care population. METHODS: We analyzed complete symptom, upper gastrointestinal (GI) endoscopy, and histology data from 1452 consecutive adult patients with GI symptoms at 2 hospitals in Hamilton, Ontario, Canada. Assessors were blinded to symptom status. Individuals with normal upper GI endoscopy and histopathology findings from analyses of biopsy specimens were classified as having no organic GI disease. The reference standard used to define the presence of true functional dyspepsia was epigastric pain, early satiety or postprandial fullness, and no organic GI disease. Sensitivity, specificity, and positive and negative likelihood ratios (LRs), with 95% confidence intervals (CIs), were calculated. RESULTS: Of the 1452 patients, 722 (49.7%) met the Rome III criteria for functional dyspepsia. Endoscopy showed organic GI disease in 170 patients (23.5%) who met the Rome III criteria. The Rome III criteria identified patients with functional dyspepsia with 60.7% sensitivity, 68.7% specificity, a positive LR of 1.94 (95% CI, 1.69-2.22), and a negative LR of 0.57 (95% CI, 0.52-0.63). In contrast, the Rome II criteria identified patients with functional dyspepsia with 71.4% sensitivity, 55.6% specificity, a positive LR of 1.61 (95% CI, 1.45-1.78), and a negative LR of 0.51 (95% CI, 0.45-0.58). The area under a receiver operating characteristics curves did not differ significantly for any of the diagnostic criteria for functional dyspepsia. CONCLUSIONS: In a validation study of 1452 patients with GI symptoms, the Rome III criteria performed only modestly in identifying those with functional dyspepsia, and were not significantly superior to previous definitions.

Validation of the Rome III criteria for the diagnosis of irritable bowel syndrome in secondary care.

BACKGROUND & AIMS: There are few validation studies of existing diagnostic criteria for irritable bowel syndrome (IBS). We conducted a validation study of the Rome and Manning criteria in secondary care. METHODS: We collected complete symptom, colonoscopy, and histology data from 1848 consecutive adult patients with gastrointestinal symptoms at 2 hospitals in Hamilton, Ontario; the subjects then underwent colonoscopy. Assessors were blinded to symptom status. Individuals with normal colonoscopy and histopathology results, and no evidence of celiac disease, were classified as having no organic gastrointestinal disease. The reference standard used to define the presence of true IBS was lower abdominal pain or discomfort in association with a change in bowel habit and no organic gastrointestinal disease. Sensitivity, specificity, and positive and negative likelihood ratios, with 95% confidence intervals, were calculated for each diagnostic criteria. RESULTS: In identifying patients with IBS, sensitivities of the criteria ranged from 61.9% (Manning) to 95.8% (Rome I), and specificities from 70.6% (Rome I) to 81.8% (Manning). Positive likelihood ratios ranged from 3.19 (Rome II) to 3.39 (Manning), and negative likelihood ratios from 0.06 (Rome I) to 0.47 (Manning). The level of agreement between diagnostic criteria was greatest for Rome I and Rome II (κ = 0.95), and lowest for Manning and Rome III (κ = 0.59). CONCLUSIONS: Existing diagnostic criteria perform modestly in distinguishing IBS from organic disease. There appears to be little difference in terms of accuracy. More accurate ways of diagnosing IBS, avoiding the need for investigation, are required.

Pathogenic factors involved in the development of irritable bowel syndrome: focus on a microbial role.

Irritable bowel syndrome (IBS) is a symptom complex characterized by recurrent abdominal pain or discomfort, and accompanied by abnormal bowel habits, in the absence of any discernible organic abnormality. Its origin remains unclear, partly because multiple pathophysiologic mechanisms are likely to be involved. A significant proportion of patients develop IBS symptoms after an episode of gastrointestinal infection. In addition to gastrointestinal pathogens, recent evidence suggests that patients with IBS have abnormal composition and higher temporal instability of their intestinal microbiota. Because the intestinal microbiota is an important determinant of normal gut function and immunity, this instability may constitute an additional mechanism that leads to symptom generation and IBS. More importantly, a role for altered microbiota composition in IBS raises the possibility of therapeutic interventions through selective antibiotic or probiotic administration. The new concept of functional bowel diseases incorporates the bidirectional communication between the gut and the central nervous system (gut-brain axis), which may explain the multiple facets of IBS by linking emotional and cognitive centers of the brain with peripheral functioning of the gastrointestinal tract and vice versa.