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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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Brain-gut-microbiota axis: challenges for translation in psychiatry
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Sundman, M., Chen, N., Subbian, V., & Chou, Y. (2017) · Brain Behavior and Immunity · doi:10.1016/j.bbi.2017.05.009 · Cited by 204
Cheng, J., Hu, H., Ju, Y., Liu, J., Wang, M., Liu, B., & Zhang, Y. (2024) · General Psychiatry · doi:10.1136/gpsych-2023-101374 · Cited by 234
Communicating systems in the body: how microbiota and microglia cooperate
Erny, D., de Angelis, A. L. H., & Prinz, M. (2016) · Immunology · doi:10.1111/imm.12645 · Cited by 195
Harnessing Gut Microbes for Mental Health: Getting From Here to There
Bruce‐Keller, A. J., Salbaum, J. M., & Berthoud, H. (2017) · Biological Psychiatry · doi:10.1016/j.biopsych.2017.08.014 · Cited by 192
Gut Microbiota and Brain Function: An Evolving Field in Neuroscience: Table 1.
Foster, J. A., Lyte, M., Meyer, E., & Cryan, J. F. (2015) · The International Journal of Neuropsychopharmacology · doi:10.1093/ijnp/pyv114 · Cited by 188
“Other combinations of probiotics have been shown to reduce a sad mood triggered by a psychological stimulus (Steenbergen et al., 2015) and to reduce depression anxiety and stress scales whilst modulating the hypothalamic pituitary adrenal (HPA) axis in petrochemical workers (Mohammadi et al., 2015).”
Effects of Probiotics on Cognitive Reactivity, Mood, and Sleep Quality
Marotta, A., Sarno, E., Del Casale, A., Pane, M., Mogna, L., Amoruso, A., Felis, G. E., & Fiorio, M. (2019) · Frontiers in Psychiatry · doi:10.3389/fpsyt.2019.00164 · Cited by 186
“In line with previous studies (12, 36, 37), we found a reduction in depressive mood state in the group that received the probiotics.”
BackgroundMethodResultInfluentialSteroids, stress and the gut microbiome-brain axis
Tetel, M. J., de Vries, G. J., Melcangi, R. C., Panzica, G., & O'Mahony, S. M. (2018) · Journal of Neuroendocrinology · doi:10.1111/jne.12548 · Cited by 187
“Steenbergen and colleagues (100) showed that a multispecies probiotic reduced negative thoughts associated with sad mood, which the authors suggest supports the concept of probiotics intervention as a preventive approach for depression (100).”
The Gut-Brain Axis, the Human Gut Microbiota and Their Integration in the Development of Obesity
Bliss, E., & Whiteside, E. (2018) · Frontiers in Physiology · doi:10.3389/fphys.2018.00900 · Cited by 196
“Additionally, probiotic treatment, in particular, treatment selective for an increase in Bifidobacterium and Lactobacilli, reduces anxiety in mice with inflammatory bowel disease, enhances cognitive reactivity to depressed mood in humans and reduces depression scores in patients with irritable bowel syndrome, as well…”
BackgroundToro-Barbosa, M. D., Hurtado‐Romero, A., García-Amezquita, L. E., & García‐Cayuela, T. (2020) · Nutrients · doi:10.3390/nu12123896 · Cited by 204
“Even though the authors did not measure any biological markers to elucidate a possible action mechanism behind the psychobiotic effect, they did state that intestinal microbiota increase plasma tryptophan levels, facilitating serotonin turnover in the brain, which has been associated with cognitive reactivity to sad m…”
BackgroundEl Hage, R., Hernandez-Sanabria, E., & Van de Wiele, T. (2017) · Frontiers in Microbiology · doi:10.3389/fmicb.2017.01889 · Cited by 185
“, 2014, 2017) through production of neuroactive substances (Steenbergen et al., 2015; Kristensen et al., 2016).”
BackgroundAshique, S., Mohanto, S., Ahmed, M. G., Mishra, N., Garg, A., Chellappan, D. K., Omara, T., Iqbal, S., & Kahwa, I. (2024) · Heliyon · doi:10.1016/j.heliyon.2024.e34092 · Cited by 205
“Results show that BDNF articulation was upgraded in cortical designs lined up with further developed longer potentiation [119].”
BackgroundRetractedTillisch, K., Mayer, E. A., Gupta, A., Gill, Z., Brazeilles, R., Le Nevé, B., van Hylckama Vlieg, J. E. T., Guyonnet, D., Derrien, M., & Labus, J. S. (2017) · Psychosomatic Medicine · doi:10.1097/psy.0000000000000493 · Cited by 185
A review of dietary and microbial connections to depression, anxiety, and stress
Taylor, A. M., & Holscher, H. D. (2018) · Nutritional Neuroscience · doi:10.1080/1028415x.2018.1493808 · Cited by 204
Majeed, M. A., Nagabhushanam, K., Arumugam, S., Majeed, S., & Ali, F. H. M. (2018) · Food & Nutrition Research · doi:10.29219/fnr.v62.1218 · Cited by 189
“This suggests that the probiotics or gut microbes may be a useful therapeutic option in stress-related disorders such as depression and anxiety (13, 20).”
BackgroundDo bacteria shape our development? Crosstalk between intestinal microbiota and HPA axis
de Weerth, C. (2017) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2017.09.016 · Cited by 189
“…decreased psychological stress, anxiety, and cortisol stress reactivity (Allen et al., 2016), reduced negative thoughts associated with sad mood (Steenbergen et al., 2015), and altered brain activity and information processing of emotional material in a brain imaging study (Tillisch et al.,…”
Stress and the gut microbiota-brain axis
Molina‐Torres, G., Rodríguez-Arrastia, M. J., Román, P., Sánchez‐Labraca, N., & Cardona, D. (2019) · Behavioural Pharmacology · doi:10.1097/fbp.0000000000000478 · Cited by 189
“significantly reduced self-reported cognitive reactivity to sad mood in depressed individuals, thus alleviating stress-induced symptoms (Steenbergen et al., 2015).”
The link between inflammation, bugs, the intestine and the brain in alcohol dependence
Leclercq, S., de Timary, P., Delzenne, N. M., & Stärkel, P. (2017) · Translational Psychiatry · doi:10.1038/tp.2017.15 · Cited by 174
Snigdha, S., Ha, K., Tsai, P., Dinan, T. G., Bartos, J. D., & Shahid, M. (2021) · Pharmacology & Therapeutics · doi:10.1016/j.pharmthera.2021.107978 · Cited by 173
The Role of Gut Dysbiosis in the Pathophysiology of Neuropsychiatric Disorders
Anand, N., Gorantla, V. R., & Chidambaram, S. B. (2022) · Cells · doi:10.3390/cells12010054 · Cited by 194
The contribution of the gut microbiome to neurodevelopment and neuropsychiatric disorders
Warner, B. B. (2018) · Pediatric Research · doi:10.1038/s41390-018-0191-9 · Cited by 171
Waclawiková, B., & El Aidy, S. (2018) · Pharmaceuticals · doi:10.3390/ph11030063 · Cited by 172
“Similarly, when healthy male and female participants (n = 20) were administered with, either a placebo product or a mixture of several probiotics strains of Bifidobacteria and Lactobacilli over a period of 4 weeks, they exhibited substantially reduced reactivity to sad mood compared to control group [129].”
BackgroundKadosh, K. C., Muhardi, L., Parikh, P., Basso, M., Mohamed, H. J. J., Prawitasari, T., Samuel, F. O., Ma, G., & Geurts, J. M. W. (2021) · Nutrients · doi:10.3390/nu13010199 · Cited by 206
Gutted! Unraveling the Role of the Microbiome in Major Depressive Disorder
Bastiaanssen, T. F. S., Cussotto, S., Claesson, M. J., Clarke, G., Dinan, T. G., & Cryan, J. F. (2020) · Harvard Review of Psychiatry · doi:10.1097/hrp.0000000000000243 · Cited by 159
Peterson, C. T. (2020) · Journal of Evidence-Based Integrative Medicine · doi:10.1177/2515690x20957225 · Cited by 160
“lactis W19 and W58 for 30 days reported reduced reactivity to sad mood, which was associated with reduced rumination and aggressive cognition, in the probiotic treated group compared to placebo group.(124) Fully understanding the mechanisms of microbiota-gut-brain axis communication will catalyze the development of mi…”
ResultMechanistic Insights into the Link between Gut Dysbiosis and Major Depression: An Extensive Review
Sonali, S., Ray, B., Hediyal, T. A., Rathipriya, A. G., Sunanda, T., Mahalakshmi, A. M., Rungratanawanich, W., Essa, M. M., Qoronfleh, M. W., Chidambaram, S. B., et al. (2022) · Cells · doi:10.3390/cells11081362 · Cited by 166
“In another study, a cocktail of probiotics, including Bifidobacterium lactis W52, Lactobacillus acidophilus W37, Bifidobacterium bifidum W23, Lactobacillus brevis W63, Lactobacillus salivarius W24, Lactobacillus casei W56, and Lactococcus lactis (W19 and W58), has shown promising results in reducing negative thoughts…”
BackgroundImpact of Environmental Pollutants on Gut Microbiome and Mental Health via the Gut–Brain Axis
Singh, S., Sharma, P., Pal, N., Kumawat, M., Shubham, S., Sarma, D. K., Tiwari, R. R., Kumar, M., & Nagpal, R. (2022) · Microorganisms · doi:10.3390/microorganisms10071457 · Cited by 161
Wei, C.-L., Wang, S., Yen, J.-T., Cheng, Y.-F., Liao, C.-L., Hsu, C.-C., Wu, C.-C., & Tsai, Y.-C. (2019) · Brain Research · doi:10.1016/j.brainres.2019.01.025 · Cited by 150
“, 2007), multi-species probiotics (Steenbergen et al., 2015), or a combination of Lactobacillus helveticus R0052 and Bifidobacterium longum R0175 (Messaoudi et al.”
Chen, Y., Fang, L., Chen, S., Zhou, H., Fan, Y., Li, L., Li, J., Xu, J., Chen, Y., Ma, Y., et al. (2020) · BioMed Research International · doi:10.1155/2020/8456596 · Cited by 153
Skonieczna‐Żydecka, K., Marlicz, W. M., Misera, A., Koulaouzidis, A., & Łoniewski, I. (2018) · Journal of Clinical Medicine · doi:10.3390/jcm7120521 · Cited by 151
“[155] demonstrated that, after 4 weeks of probiotic supplementation, a statistically significant improvement of aggression and rumination compared to placebo was found.”
BackgroundThe Relationship Between the Gut Microbiome-Immune System-Brain Axis and Major Depressive Disorder
Foster, J. A., Baker, G. B., & Dursun, S. M. (2021) · Frontiers in Neurology · doi:10.3389/fneur.2021.721126 · Cited by 161
A potential role for the gut microbiome in substance use disorders
Meckel, K. R., & Kiraly, D. D. (2019) · Psychopharmacology · doi:10.1007/s00213-019-05232-0 · Cited by 146
“Butyrate, in particular, is known to be a potent HDAC inhibitor, and other SCFAs such as propionate have also demonstrated HDAC inhibition (Stilling et al. 2014; Koh et al. 2016).”
Role of the intestinal microbiome, intestinal barrier and psychobiotics in depression
Trzeciak, P., & Herbet, M. (2021) · Nutrients · doi:10.3390/nu13030927 · Cited by 139
Targeting gut microbiome: a novel and potential therapy for autism
Yang, Y., Tian, J., & Yang, B. (2018) · Life Sciences · doi:10.1016/j.lfs.2017.12.027 · Cited by 140
Sánchez, M., Darimont, C., Panahi, S., Drapeau, V., Marette, A., Taylor, V. H., Doré, J., & Tremblay, A. (2017) · Nutrients · doi:10.3390/nu9030284 · Cited by 138
“While the present study did not examine the biological mechanisms responsible for the beneficial effects on mood, a number of hypotheses have been made, including an increase in plasma tryptophan concentrations leading to a facilitation of serotonin turnover in the brain, and an improvement in the epithelial barrier f…”
BackgroundYang, Z., Li, J., Gui, X., Shi, X., Bao, Z., Han, H., & Li, M. D. (2020) · Molecular Psychiatry · doi:10.1038/s41380-020-0729-1 · Cited by 139
“(W19 and W58), it was found that 4-week probiotic intervention significantly reduced overall cognitive reactivity to sad mood in comparison with the participants receiving placebo [100].”
Result
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
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