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   ScienceDirect    
   Brain, Behavior, and Immunity    
   Available online 7 April 2015, doi:10.1016/j.bbi.2015.04.003    
   Open Access, Creative Commons license    
   In Press, Corrected Proof — Note to users    
      
      
   A randomized controlled trial to test the effect of multispecies probiotics on   
   cognitive reactivity to sad mood ☆    
      
   Laura SteenbergenRoberta SellaroLorenza S. Colzato    
   Show more    
   Highlights    
   •    
   Multispecies probiotic supplementation reduced cognitive reactivity to sad   
   mood.    
   •    
   Strongest effects for reduced rumination and reduced aggressive thoughts.    
   •    
   Multispecies probiotics may be used as potential preventive strategy for   
   depression.    
   Abstract    
   Background: Recent insights into the role of the human microbiota in cognitive   
   and affective functioning have led to the hypothesis that probiotic   
   supplementation may act as an adjuvant strategy to ameliorate or prevent   
   depression. Objective: Heightened    
   cognitive reactivity to normal, transient changes in sad mood is an   
   established marker of vulnerability to depression and is considered an   
   important target for interventions. The present study aimed to test if a   
   multispecies probiotic containing    
   Bifidobacterium bifidum W23, Bifidobacterium lactis W52, Lactobacillus   
   acidophilus W37, Lactobacillus brevis W63, Lactobacillus casei W56,   
   Lactobacillus salivarius W24, and Lactococcus lactis (W19 and W58) may reduce   
   cognitive reactivity in non-depressed    
   individuals. Design: In a triple-blind, placebo-controlled, randomized, pre-   
   and post-intervention assessment design, 20 healthy participants without   
   current mood disorder received a 4-week probiotic food-supplement intervention   
   with the multispecies    
   probiotics, while 20 control participants received an inert placebo for the   
   same period. In the pre- and post-intervention assessment, cognitive   
   reactivity to sad mood was assessed using the revised Leiden index of   
   depression sensitivity scale. Results:    
   Compared to participants who received the placebo intervention, participants   
   who received the 4-week multispecies probiotics intervention showed a   
   significantly reduced overall cognitive reactivity to sad mood, which was   
   largely accounted for by reduced    
   rumination and aggressive thoughts. Conclusion: These results provide the   
   first evidence that the intake of probiotics may help reduce negative thoughts   
   associated with sad mood. Probiotics supplementation warrants further research   
   as a potential    
   preventive strategy for depression.    
      
   Keywords    
   ProbioticsDepressionCognitive reactivity    
   1 Introduction    
   The intestine and the brain are intimately connected via the brain-gut axis,   
   which involves bidirectional communication via neural, endocrine and immune   
   pathways (Grossman, 1979, Grenham et al., 2011, Mayer, 2011 and Mayer et al.,   
   2014). In recent years    
   it has become increasingly evident that this communication also involves   
   interactions with the intestinal microbiota, which release immune activating   
   and other signaling molecules that may play an important role in regulating   
   the brain and subsequent    
   behavior (Mayer, 2011, Cryan and Dinan, 2012 and Foster and McVey Neufeld,   
   2013). For example, the microbiota produce neuroactive substances and their   
   precursors (e.g., tryptophan) which can reach the brain via endocrine and   
   afferent autonomic pathways (   
   Desbonnet et al., 2008 and Desbonnet et al., 2010). Also, bacterial products,   
   such as the gram-negative endotoxins, can influence mood and cognitive   
   functions via indirect (e.g., immune activation) and direct (e.g., Toll-like   
   receptors on glial cells)    
   mechanisms (Lehnardt et al., 2003, Krabbe et al., 2005, Ait-Belgnaoui et al.,   
   2012 and McCusker and Kelley, 2013).    
      
   These novel insights have fuelled the hypothesis that modification of   
   microbial ecology, for example by supplements containing microbial species   
   (probiotics), may be used therapeutically to modify stress responses and   
   symptoms of anxiety and depression (   
   Logan and Katzman, 2005, Cryan and O’Mahony, 2011 and Bruce-Keller et al.,   
   2015). While most of this research is relatively recent, and predominantly   
   involves animal and pre-clinical human studies, the results appear in support   
   of this hypothesis (   
   Logan and Katzman, 2005, Cryan and Dinan, 2012, Foster and McVey Neufeld,   
   2013, Tillisch, 2014 and Savignac et al., 2015). For instance, Bravo et al.   
   (2011) observed a reduction in anxious and depressive behavior after feeding   
   healthy mice with    
   Lactobacillus rhamnosus JB-1. Similarly, Desbonnet et al. (2010) observed a   
   reduction in depressive-like behaviors in adult rats after feeding them with   
   Bifidobacterium infantis 35624. This reduction was comparable to the effects   
   of administering the    
   antidepressant citalopram (Desbonnet et al., 2010). Probiotic studies in   
   humans are still scarce, but the available data are promising. For example,   
   Benton et al. (2006) found in a non-clinical sample that a 3-week intervention   
   with probiotics-containing    
   milk drink (i.e., Lactobacillus casei Shirota) improved mood scores compared   
   to participants who received a placebo intervention. Improvement in mood was   
   only observed for participants who showed elevated symptoms of depression at   
   baseline. In another    
   pre-clinical study it was demonstrated that participants who were given a   
   mixture of probiotics containing Lactobacillus helveticus R0052 and   
   Bifidobacterium longum R0175 showed significantly less psychological distress   
   than matched controls (Messaoudi    
   et al., 2011). Furthermore, Rao et al. (2009) demonstrated that patients with   
   chronic fatigue syndrome, which is often comorbid with anxiety disorders,   
   reported significantly less anxiety symptoms after ingestion of a daily dose   
   of L. casei Shirota for 2    
   months, as compared to a placebo group. On the basis of these and other   
   results it has been suggested that probiotics may serve as adjuvant or   
   preventive therapy for depression (for reviews see Logan and Katzman, 2005,   
   Cryan and Dinan, 2012, Foster and    
   McVey Neufeld, 2013 and Tillisch, 2014).    
      
      
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