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A randomized controlled trial to test the effect of multispecies probiotics on cognitive reactivity to sad mood
Open accessAbstract
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.
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“Several studies in healthy participants have demonstrated reduced stress-induced cortisol levels and pro-inflammatory cytokines, along with improved cognitive test performance, perceptions of stress, anxiety, and mood (465–469).”
From Signalling cognition: The gut microbiota and hypothalamic-pituitary-adrenal axis (2023) · cites this paper as [468]
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“Various Lactobacillus strains, or Lactobacillus-containing supplements, have been shown to reduce depressive-like behaviour in rodents [1, 13, 23, 44, 45] and improve measures of depression in humans [3, 5, 39, 76].”
From Distinct actions of the fermented beverage kefir on host behaviour, immunity and microbiome gut-brain modules in the mouse (2020) · cites this paper as [76]
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“…that individuals who typically respond to low mood by ruminating about possible causes and consequences of their state have more difficulties in recovering from depression (Nolen-Hoeksema et al., 1993; Kuehner and Weber, 1999; Nolen-Hoeksema, 2000; Spasojevic and Alloy, 2001; Moulds et al., 2008).”
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BackgroundInfluentialObese-type gut microbiota induce neurobehavioral changes in the absence of obesity
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BackgroundInfluentialNeuroimaging of the brain–gut axis: From basic understanding to treatment of functional GI disorders
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Bifidobacteria modulate cognitive processes in an anxious mouse strain
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“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; Savignac et al., 2015).”
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“E-mail addresses: L.Steenbergen@fsw.leidenuniv.nl (L. Steenbergen), R.Sellaro@ fsw.leidenuniv.nl (R. Sellaro), S.vanHemert@winclove.nl (S. van Hemert), J.A.Bosch@ uva.nl (J.A. Bosch), Colzato@fsw.leidenuniv.nl (L.S. Colzato).”
BackgroundResultInfluentialCognitive reactivity to sad mood: structure and validity of a new measure
van der Does, W. A. J. (2002) · Behaviour Research and Therapy · doi:10.1016/s0005-7967(00)00111-x · Cited by 215 · cited 2×
“The total score is calculated by adding-up all items, hence scores range between 0 and 63 (0–13: minimal depression, 14–19: mild depression, 20–28: moderate depression and 29–63: severe depression; van der Does, 2002a).”
MethodLow-dose endotoxemia and human neuropsychological functions
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“⇑ Corresponding author at: Leiden University, Institute for Psychological Research, Cognitive Psychology, Wassenaarseweg 52, 2333 AK Leiden, The Netherlands.”
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“Internal consistency (Cronbach’s alpha; a) is 0.89 for the LEIDS total score, and ranges between 0.62 (Acceptance/Coping) and 0.84 for the subscales (Hopelessness/Suicidality; Antypa and van der Does, 2010; Williams et al., 2008).”
BackgroundInfluentialClassification Trees Distinguish Suicide Attempters in Major Psychiatric Disorders
Mann, J. J., Ellis, S. P., WATERNAUX, C. M., Liu, X., Oquendo, M. A., Malone, K. M., Brodsky, B. S., Haas, G. L., & Currier, D. (2008) · The Journal of Clinical Psychiatry · doi:10.4088/jcp.v69n0104 · Cited by 149
The effects of gut microbiota on CNS function in humans
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“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; Tillisch, 2014).”
BackgroundResultColzato, L. S., Hertsig, G., van den Wildenberg, W. P. M., & Hommel, B. (2010) · Neuroscience · doi:10.1016/j.neuroscience.2010.02.029 · Cited by 143
Self-citationForebrain parasympathetic control of heart activity: retrograde transneuronal viral labeling in rats
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“Animal studies have further suggested that gut-to-brain signals are transmitted via the vagus nerve (Ter Horst and Postema, 1997; Tillisch et al., 2013).”
BackgroundKoning, C. J., Jonkers, D. M. A. E., Stobberingh, E. E., Mulder, L. H. C., Rombouts, F. M., & Stockbrügger, R. W. (2007) · The American Journal of Gastroenterology · doi:10.1111/j.1572-0241.2007.01547.x · Cited by 100
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“These genera have been found to be effective in ameliorating anxious and depressive symptoms (Benton et al., 2006; Rao et al., 2009; Yamamura et al., 2009; Desbonnet et al., 2010; Bravo et al., 2011; Messaoudi et al., 2011).”
BackgroundThought suppression and cognitive vulnerability to depression
van der Does, W. A. J. (2005) · British Journal of Clinical Psychology · doi:10.1348/014466504x19442 · Cited by 91 · cited 4×
“…reactivity to transient changes in sad mood was measured by means of the revised Leiden Index of Depression Sensitivity (LEIDS-r; van der Does and Williams, 2003), which has been shown to be predictive of depression in multiple longitudinal studies (van der Does, 2005; Kruijt et al., 2013).”
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“Interestingly, cognitive reactivity to sad mood has been associated with serotonin concentrations, with higher scores correlating with lower serotonin levels (Booij and Van der Does, 2007; Wells et al., 2010; see also Firk and Markus, 2009).”
BackgroundEffect of the rehydration medium on the recovery of freeze-dried lactic acid bacteria
de Valdez, G. F., de Giori, G. S., Holgado, A. P. D. R., & Oliver, G. (1985) · Applied and Environmental Microbiology · doi:10.1128/aem.50.5.1339-1341.1985 · Cited by 73 · cited 1×
“The batch used for the present experiments contained >2.5 109 CFU/g, whereas the placebo contained 1 104 CFU/g. Rehydration of freeze-dried lactic acid bacteria in milk, water and physiological salt solution has been shown to result in equal survival rates (de Valdez et al., 1985).”
MethodInfluentialAn Investigation of the Relationship Between Cognitive Reactivity and Rumination
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“Internal consistency (Cronbach’s alpha; a) is 0.89 for the LEIDS total score, and ranges between 0.62 (Acceptance/Coping) and 0.84 for the subscales (Hopelessness/Suicidality; Antypa and van der Does, 2010; Williams et al., 2008).”
BackgroundInfluentialGut Pathogens: enteric health at the interface of changing microbiology
Ahmed, N., Sechi, L. A., Mégraud, F., & Hasnain, S. E. (2009) · Gut Pathogens · doi:10.1186/1757-4749-1-1 · Cited by 69
Neural and Hormonal Regulation of Gastrointestinal Function: An Overview
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“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; Mayer et al., 2014).”
BackgroundCognitive and serotonergic vulnerability to depression: Convergent findings.
Booij, L., & van der Does, W. A. J. (2007) · Journal of Abnormal Psychology · doi:10.1037/0021-843x.116.1.86 · Cited by 55 · cited 2×
“…found to predict depression incidence in multiple longitudinal studies and to correlate with depression risk factors, such as depression history (Moulds et al., 2008), genetic markers of depression (Antypa and van der Does, 2010), and reaction to tryptophan depletion (Booij and van der Does, 2007).”
BackgroundPsychometric properties of the Leiden Index of Depression Sensitivity (LEIDS).
Solis, E. C., Antypa, N., Conijn, J. M., Kelderman, H., & van der Does, W. A. J. (2016) · Psychological Assessment · doi:10.1037/pas0000326 · Cited by 54
Kruijt, A.-W., Antypa, N., Booij, L., de Jong, P. J., Glashouwer, K., Penninx, B. W. J. H., & Van der Does, W. (2013) · PLoS ONE · doi:10.1371/journal.pone.0070245 · Cited by 49
Stress modulation of visuomotor binding
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“The M.I.N.I. is a short structured interview, taking about 15 min, which screens for several psychiatric disorders (Sheehan et al., 1998; Colzato et al., 2008, 2010).”
BackgroundSelf-citationClinical Studies Evaluating Effects of Probiotics on Parameters of Intestinal Barrier Function
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“Thus, our results show that the intake of multispecies probiotics for a 4-week period significantly reduced overall cognitive reactivity to depression and in particular aggressive and ruminative thoughts.”
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Intestinal permeability measurements: general aspects and possible pitfalls.
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De Beck Depression Inventory (BDI).
Bouman, T. K. (1994) · University of Groningen research database (University of Groningen / Centre for Information Technology) · Cited by 21
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“Each bacterial strain of the multispecies probiotics used in this study has been found to improve epithelial barrier function both when tested separately and in combination (Van Hemert and Ormel, 2014).”
BackgroundThe role of vagal function in the prevention of and risk for cardiovascular disease and mortality
Thayer, J. F., & Lane, R. D. (2006) · European Journal of Cardiovascular Prevention & Rehabilitation · doi:10.1097/00149831-200605001-00124 · Cited by 4
Flagged first, then by citations
4 of the 80 references couldn’t be matched to a known paper.
Cited by
Sorted by citations
Cryan, J. F., O'Riordan, K. J., Cowan, C. S. M., Sandhu, K. V., Bastiaanssen, T. F. S., Boehme, M., Codagnone, M. G., Cussotto, S., Fulling, C., Golubeva, A. V., et al. (2019) · Physiological Reviews · doi:10.1152/physrev.00018.2018 · Cited by 5,286
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“…of small studies in healthy individuals suggest pre- and probiotic consumption can positively affect aspects of mood and anxiety (Messaoudi et al., 2011; Steenbergen et al., 2015), modulate HPA function (Messaoudi et al., 2011; Schmidt et al., 2015) and alter brain activity (Tillisch et al., 2013).”
BackgroundMartin, C. R., Osadchiy, V., Kalani, A., & Mayer, E. A. (2018) · Cellular and Molecular Gastroenterology and Hepatology · doi:10.1016/j.jcmgh.2018.04.003 · Cited by 1,284
Stress & the gut-brain axis: Regulation by the microbiome
Foster, J. A., Rinaman, L., & Cryan, J. F. (2017) · Neurobiology of Stress · doi:10.1016/j.ynstr.2017.03.001 · Cited by 1,150
The microbiome-gut-brain axis in health and disease
Dinan, T. G., & Cryan, J. F. (2017) · Gastroenterology Clinics of North America · doi:10.1016/j.gtc.2016.09.007 · Cited by 1,111
Metadata
- Authors
- Steenbergen, L., Sellaro, R., van Hemert, S., Bosch, J. A., & Colzato, L. S.
- Affiliations
- Leiden University (NL)
- University of Amsterdam (NL)
- Corresponding author
- Steenbergen, Laura
- Venue
- Brain, Behavior, and Immunity
- Publisher
- Elsevier BV
- Published
- 2015-08
- Volume
- 48
- Pages
- 258-264
- ISSN
- 0889-1591 (ISSN-L)
- OpenAlex
- W1978433534
- Cited by
- 671
- References
- 80
- Citations by year
- 2026: 26 · 2025: 44 · 2024: 58 · 2023: 52 · 2022: 73 · 2021: 72 · 2020: 88 · 2019: 68 · 2018: 65 · 2017: 59 · 2016: 51 · 2015: 15
- FWCI
- 84.76
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Brain Behavior and Immunity (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- Pure Amsterdam UMC (publishedVersion, other-oa)
- Leiden Repository (Leiden University) (submittedVersion)
- UvA-DARE (University of Amsterdam) (submittedVersion, cc-by-nc-nd)
- Padua Research Archive (University of Padova) (submittedVersion, cc-by-nc-nd)
- Data Archiving and Networked Services (DANS) (submittedVersion)
- Data Archiving and Networked Services (DANS) (submittedVersion, other-oa)
- Funders
- Nederlandse Organisatie voor Wetenschappelijk Onderzoek (452-12-001)
- Topics
- Life Sciences › Agricultural and Biological Sciences › Food Science › Probiotics and Fermented Foods
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gut microbiota and health
- Life Sciences › Neuroscience › Biological Psychiatry › Tryptophan and brain disorders
- Keywords
- multispecies probiotics, depression vulnerability, rumination, aggressive thoughts, Bifidobacterium bifidum, Bifidobacterium animalis subsp. lactis, Lactobacillus, Lactococcus lactis, gut microbiota, depression prevention, probiotic supplementation
- MeSH terms
- Adolescent, Affect, Bifidobacterium, Cognition, Depressive Disorder, Double-Blind Method, Female, Humans, Lactobacillus, Lactobacillus acidophilus, Male, Social Behavior, Dietary Supplements, Probiotics, Young Adult
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
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