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

Research Glimpse: Animal studies indicate probiotics affect various behaviors as well as alter neurochemistry of different brain regions. Several human clinical trials also suggest probiotics influence different behaviors including anxiety, depressive symptoms, abnormal pain perception and altered cognitive reactivity to sad mood. Probiotics can treat the gastrointestinal symptoms of IBS but it is not yet known how they affect the comorbid symptoms of mental illness.

This randomized controlled pilot study investigated the effect of probiotic Bifidobacterium longum NCC3001 on depressive symptoms in patients diagnosed with both IBS (diarrhea and mixed subtypes, Rome III criteria) and mild to moderate anxiety and/or depression (Hospital Anxiety and Depression Scale, HADS).

For six weeks daily, the intervention group consumed 100-200ml of preheated (20C) milk (lactose-free, soy or rice) containing 1 gram of spray-dried powder consisting of 1X1010 cfus B. longum NCC3001 and maltodextrin. The placebo group consumed milk containing only 1 gram of maltodextrin; considered indistinguishable in package, color, taste and consistency. At time zero and at six weeks, both groups had numerous different parameters tested and analyzed, see Table 1.

At the end of the study, twice as many patients in the probiotic group had significantly decreased depressive symptom scores compared to placebo, in addition to some improvement in quality of life scores (Table 1). These patients also had significant changes in activity of regions of the brain associated with detection and response to fearful stimuli as well as visceral sensitivity. Excretion of several urinary metabolites was reduced in the probiotic group but only 4-cresol sulfate correlated with the depression scores. Because 4-cresol sulfate inhibits the enzyme converting dopamine into noradrenaline (i.e. dopamine β-hydroxylase) and has reduced activity in patients with depression in some studies, this might be part of the mechanism of action of the probiotic.

Study strengths include a robust study design (eg. selection of probiotic and outcome measures based on a previous animal study), the use of intention to treat principles to analyze the primary outcome, strict inclusion and exclusion criteria and a diverse range of secondary endpoints examined using state-of-the-art diagnostic technology and validated subjective criteria (Table 1).

Some limitations of this study include limited statistical power due to the small sample size (n=22); restriction to only certain subtypes of IBS (i.e. the results are not directly applicable to all patients with IBS); and a notable difference in baseline depression scores between the two groups. Moreover, participants in this study already had an altered brain gut axis, as indicated by diagnosis of both IBS and mild to moderate anxiety. Other patients with depression, and no overt signs of GIT involvement, might not have the same effect when ingesting probiotics. Moreover, the probiotic strain, vehicle used (i.e. preheated milk), maltodextrin (rather than established prebiotics including fructo-oligosaccharides, inulin, or galacto-oligosaccharides) is unique compared to other human studies examining the effect of probiotics on human mood and symptoms of mental illness, minimizing the validity of any direct comparison.

Nevertheless, this is the first RCT to demonstrate that a probiotic could influence co-morbid symptoms of mental illness associated with IBS, in addition to altering activity in a multiple brain regions associated with processing of emotions (eg. amygdala and fronto-limbic regions). Further well-designed metabolomics studies are needed to confirm the finding of reduced urinary excretion of 4 cresol as well as determine whether this is clinically meaningful. The results of this study are promising. However, additional clinical trials are needed establish whether probiotics are efficacious as adjuvant treatments for patients with isolated or comorbid symptoms of mental illness.

Reference: Pinto-Sanchez MI, Hall GB, Ghajar K et al. Probiotic Bifidobacterium longum NCC3001 Reduces Depression Scores and Alters Brain Activity: a Pilot Study in Patients With Irritable Bowel Syndrome, Gastroenterology 2017. May 5. pii: S0016-5085(17)35557-9. doi: 10.1053/j.gastro.2017.05.003. [Epub ahead of print]

Table 1: Outcome measures tested at time zero and following six weeks consumption of Bifidobacterium longum NCC3001
- Please refer to attached images at top left of this blog for Table 1 Primary and Secondary Outcome Measures