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.


      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.


      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.


      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. no. NCT01276626.


      Abbreviations used in this paper:

      ANCOVA (analysis of covariance), BDNF (brain-derived neurotrophic factor), BL (Bifidobacterium longum NCC3001), BOLD (Blood Oxygen Level Dependent), CGRP (calcitonin gene-related peptide), CI (confidence interval), CRP (C-reactive protein), FDR (false discovery rate), fMRI (functional magnetic resonance imaging), GLM (general linear model), HAD (Hospital Anxiety and Depression), HAD-D (HAD-depression), HPA (hypothalamic-pituitary-adrenal), 5-HT (5-hydroxytryptamine), IBS (irritable bowel syndrome), IL (interleukin), ITT (intention-to-treat), NMR (nuclear magnetic resonance), OPLS (orthogonal projection to latent structures), OPLS-DA (OPLS discriminant analysis), PP (per-protocol evaluation), QoL (quality of life), ROI (region of interest), RR (relative risk), rRNA (ribosomal RNA), SF-36 (Short Form Health Survey), STAI (State-Trait Anxiety Inventory)
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