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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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Łoniewski, I., Skonieczna‐Żydecka, K., Sołek-Pastuszka, J., & Marlicz, W. M. (2022) · Journal of Clinical Medicine · doi:10.3390/jcm11175155 · Cited by 22
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“Food supplementation with a multispecies probiotic has been proposed as a strategy to reduce negative thoughts associated with sad mood; therefore, it represents a potential preventive strategy for depression (Steenbergen et al., 2015).”
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PROBIOTICS, PSYCHOBIOTICS, AND METABIOTICS: PROBLEMS AND PROSPECTS
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“salivarius W24, Lactococcus lactis W19 и W58), после которого испытуемые, по данным анкетирования, в меньшей мере по сравнению с контрольной группой (получавшей пла цебо) проявляли агрессивность, руминацию (длительные тягостные размышления) и другие негативные когнитивные реакции в ответ на неприятные психологические…”
Analysis of gut microbiota and depression and anxiety: Mendelian randomization from three datasets
Lai, Y., & Xiong, P. (2025) · General Hospital Psychiatry · doi:10.1016/j.genhosppsych.2025.03.012 · Cited by 20
Pan, B., Pan, Y., Huang, Y., Yi, M., Hu, Y., Lian, X., Shi, H., Wang, M., Xiang, G., Yang, W., et al. (2025) · BMC Psychiatry · doi:10.1186/s12888-024-06438-z · Cited by 21
Lai, C., Chen, C., She, S.-C., Chen, W., Kuo, T. B. J., Lin, H., & Yang, C. C. H. (2021) · Life Sciences · doi:10.1016/j.lfs.2021.120165 · Cited by 20
Nasr, N. (2018) · International Journal of Current Microbiology and Applied Sciences · doi:10.20546/ijcmas.2018.708.296 · Cited by 19
Food Components with the Potential to be Used in the Therapeutic Approach of Mental Diseases
Fernández, M. J. F., Valero‐Cases, E., & Frutos‐Rincón, L. (2018) · Current Pharmaceutical Biotechnology · doi:10.2174/1389201019666180925120657 · Cited by 20
Oluwagbemigun, K., Schnermann, M. E., Schmid, M. C., Cryan, J. F., & Nöthlings, U. (2022) · Gut Pathogens · doi:10.1186/s13099-022-00487-z · Cited by 20
Mutoh, N., Kakiuchi, I., Hiraku, A., Iwabuchi, N., Kiyosawa, K., Igarashi, K., Tanaka, M., Nakamura, M., & Miyasaka, M. (2023) · Beneficial Microbes · doi:10.3920/bm2022.0048 · Cited by 21
Yang, X., Zhao, Y., Xue, L., Wang, H., Zeng, J., Du, J., & Xu, Z. (2023) · Journal of Integrative Neuroscience · doi:10.31083/j.jin2204092 · Cited by 19
Kou, J., Kang, H., Hu, L., Wang, D., Wang, S., Wang, Q., & Yang, Z. (2023) · Geriatric Nursing · doi:10.1016/j.gerinurse.2023.09.009 · Cited by 21
Hashemi-Mohammadabad, N., Taghavi, S.-A., Lambert, N., Moshtaghi, R., Bazarganipour, F., & Sharifi, M. (2024) · BMC Psychiatry · doi:10.1186/s12888-023-05429-w · Cited by 20
“Steenbergen et al. (2015) conducted a randomized trial that evaluated the effects of probiotics on cognitive reactivity to sad mood using the Leiden index of depression sensitivity.”
MethodDissecting the biology of feeding and eating disorders
Huckins, L. M., Brennand, K., & Bulik, C. M. (2024) · Trends in Molecular Medicine · doi:10.1016/j.molmed.2024.01.009 · Cited by 20
Borkent, J., Ioannou, M., Neijzen, D., Haarman, B. C. M., & Sommer, I. E. (2024) · Schizophrenia Bulletin · doi:10.1093/schbul/sbae188 · Cited by 24
“Emerging evidence from preclinical studies, 11,12 as well as clinical populations, 13,14 suggests that probiotics may improve psychiatric symptoms and cognitive functioning, offering a novel avenue for intervention in BD and SSD.”
Cook, J., Lehne, C., Weiland, A., Archid, R., Ritze, Y., Bauer, K., Zipfel, S., Penders, J., Enck, P., & Mack, I. (2020) · Nutrients · doi:10.3390/nu12082396 · Cited by 20
The Viral Janus: Viruses as Aetiological Agents and Treatment Options in Colorectal Cancer
Turkington, C. J. R., Varadan, A. C., Grenier, S. F., & Grasis, J. A. (2021) · Frontiers in Cellular and Infection Microbiology · doi:10.3389/fcimb.2020.601573 · Cited by 19
“Critical traits from our metabolic profiles, immune responses, to even our moods are all shaped by microbes in the gut (Turnbaugh et al., 2006; Steenbergen et al., 2015; Spencer et al., 2019).”
BackgroundRenson, A., Kasselman, L. J., Dowd, J. B., Waldron, L., Jones, H. E., & Herd, P. (2020) · Brain Behavior & Immunity - Health · doi:10.1016/j.bbih.2020.100155 · Cited by 20
“…general mood, like depressive symptoms, anxiety or anger (Jiang et al., 2015; Kelly et al., 2016; Valles-Colomer et al., 2019) or studied indirect links to mood, such as probiotic use (Huang et al., 2016; Jiang et al., 2015; Slykerman et al., 2017; Steenbergen et al., 2015; Tillisch et al., 2013).”
BackgroundInfluentialProbiotics-targeting new milestones from gut health to mental health
Dey, G., & Mookherjee, S. (2021) · FEMS Microbiology Letters · doi:10.1093/femsle/fnab096 · Cited by 18
Yao, Y., Qi, X., Jia, Y., Ye, J., Chu, X., Wen, Y., Cheng, B., Cheng, S., Liu, L., Liang, C., et al. (2022) · Psychological Medicine · doi:10.1017/s0033291721005092 · Cited by 19
Zhu, J., Zhu, Y., & Song, G. (2023) · Microorganisms · doi:10.3390/microorganisms11061403 · Cited by 21
“lus fermentum W56, Lactobacillus salivarius W24, and others, significantly reduces overall cognitive responses to sad emotions, mainly due to a decrease in aggressive thinking [51].”
BackgroundChan, H. H. Y., Siu, P. L. K., Choy, C. T., Chan, U. K., Zhou, J., Wong, C. H., Lee, Y. W., Chan, H. W., Tsui, J. C. C., Loo, S. K. F., et al. (2023) · Nutrients · doi:10.3390/nu15245037 · Cited by 18
“Gut–brain axis”: Review of the role of the probiotics in anxiety and depressive disorders
Gambaro, E., Gramaglia, C. M., Baldon, G., Chirico, E., Martelli, M. I., Renolfi, A., & Zeppegno, P. (2020) · Brain and Behavior · doi:10.1002/brb3.1803 · Cited by 21
Lengvenytė, A., Strumila, R., Maı̈moun, L., Sénèque, M., Olié, É., Lefebvre, P., Renard, É., Courtet, P., & Guillaume, S. (2021) · Eating and Weight Disorders - Studies on Anorexia Bulimia and Obesity · doi:10.1007/s40519-021-01180-x · Cited by 20
“Biologically, changes in the hippocampus neuroplasticity [44], and differences in the responses to negative emotional stimuli in relation to gut microbiota have been described [45].”
BackgroundThe Microbiota-gut-immune-glia (MGIG) Axis in Major DepressionPreprint
Rudzki, L., & Maes, M. H. J. (2020) · Preprints.org · doi:10.20944/preprints202002.0084.v1 · Cited by 18
Role of the gut microbiome in psychological symptoms associated with inflammatory bowel diseases
Atanasova, K., Knödler, L.-L., Reindl, W., Ebert, M. P. A., & Thomann, A. (2025) · Seminars in Immunopathology · doi:10.1007/s00281-025-01036-x · Cited by 19
Sabouri, S., Esmailzadeh, M., Sadeghinejad, A., Shahrbabaki, M. E., Asadikaram, G., & Nikvarz, N. (2022) · Journal of Psychiatric Practice · doi:10.1097/pra.0000000000000660 · Cited by 19
Queuosine tRNA Modification: Connecting the Microbiome to the Translatome
Rashad, S. (2024) · BioEssays · doi:10.1002/bies.202400213 · Cited by 16
Browne, P., Bolte, A., Claassen, E., & de Weerth, C. (2019) · Trials · doi:10.1186/s13063-019-3389-1 · Cited by 16
Qi, Q., Liu, H., Yang, Y., Wang, Y., Xia, C., Tian, P., Wei, J., Li, S., & Chen, T. (2021) · Disease Markers · doi:10.1155/2021/5597401 · Cited by 17
RetractedExploring the complex interplay: gut microbiome, stress, and leptospirosis
Petakh, P., Oksenych, V., Kamyshna, I. I., Boisak, I., Lyubomirskaya, K., & Kamyshnyi, O. (2024) · Frontiers in Microbiology · doi:10.3389/fmicb.2024.1345684 · Cited by 16
The essentials of a global index for cognitive function
Antony, J. M., Weaver, I. C. G., Rueffer, M., Guthrie, N., & Evans, M. (2017) · Translational Neuroscience · doi:10.1515/tnsci-2017-0014 · Cited by 16
Is there a role of gut microbiota in mental health?
Lange, K. W., Lange, K. M., Nakamura, Y. K., & Kanaya, S. (2020) · Journal of Food Bioactives · doi:10.31665/jfb.2020.9213 · Cited by 17
“In humans, randomized trials have revealed beneficial effects of probiotics on mood (Messaoudi, 2011; Steenbergen, 2015).”
BackgroundFermented Foods and the Gut Microbiome
Heinen, E., Ahnen, R. T., & Slavin, J. L. (2020) · Nutrition Today · doi:10.1097/nt.0000000000000422 · Cited by 16
Microbiota-Gut-Brain Axis and Antidepressant Treatment
Lachmansingh, D. A., Lavelle, A., Cryan, J. F., & Clarke, G. A. (2023) · Current topics in behavioral neurosciences · doi:10.1007/7854_2023_449 · Cited by 17
It’s Dead! Can Postbiotics Really Help Performance and Recovery? A Systematic Review
Kerksick, C. M., Moon, J. M., & Jäger, R. (2024) · Nutrients · doi:10.3390/nu16050720 · Cited by 15
“…benefits exists for probiotic use including improvements in gut health [2], mood [3,4], stress, depression [4] and other aspects of mental health [4,5], sleep quantity and quality [3,6], immune system function [7], oral health [8,9], management of allergies [10], and cardiovascular health [11].”
BackgroundAmaral, W. Z., Kokroko, N., Treangen, T. J., Villapol, S., & Gómez‐Pinilla, F. (2024) · Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease · doi:10.1016/j.bbadis.2024.167483 · Cited by 15
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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