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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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Infant Gut Microbiota Associated with Fine Motor Skills
Acuña, I., Cerdó, T., Ruiz-Rodriguez, A., Torres-Espínola, F. J., López‐Moreno, A., Aguilera, J., Suárez, A., & Campoy, C. (2021) · Nutrients · doi:10.3390/nu13051673 · Cited by 41
“For instance, in a recent randomised controlled trial [48], healthy male and female participants consumed either a placebo product or a mixture of several probiotics (B.”
BackgroundShabbir, M. A., Mehak, F., Khan, Z. M., Ahmed, W., Haq, S. M. A. U., Khan, M. R., Bhat, Z. F., & Aadil, R. M. (2022) · Trends in Food Science & Technology · doi:10.1016/j.tifs.2021.12.035 · Cited by 47
Ullah, H., Khan, A., Rengasamy, K. R. R., Minno, A. D., Sacchi, R., & Daglia, M. (2022) · Nutrients · doi:10.3390/nu14132751 · Cited by 47
“Steenbergen et al. (2015) demonstrated the effects of a multispecies probiotic supplement (Bifidobacterium lactis W52, B. bifidum W23, Lactobacillus acidophilus W37, L. brevis W63, L. casei W56, L. salivarius W24, and L. lactis W19, and L. lactis W58) in the amelioration of cognitive reactivity to…”
BackgroundThe Role of Inflammation in the Pathophysiology of Depression and Suicidal Behavior
Serafini, G., Costanza, A., Aguglia, A., Amerio, A., Trabucco, A., Escelsior, A., Sher, L., & Amore, M. (2022) · Medical Clinics of North America · doi:10.1016/j.mcna.2022.09.001 · Cited by 48
Dahiya, D., & Nigam, P. S. (2022) · Microorganisms · doi:10.3390/microorganisms10091687 · Cited by 40
Li, J., Li, Y., Zhao, J., Li, L., Wang, Y., Chen, F., Li, Y., Cheng, R., He, F., Ze, X., et al. (2024) · European Journal of Nutrition · doi:10.1007/s00394-024-03447-2 · Cited by 49
Effects of Probiotics and Prebiotics on Frailty and Ageing: A Narrative Review
Jayanama, K., & Theou, O. (2019) · Current Clinical Pharmacology · doi:10.2174/1574884714666191120124548 · Cited by 43
Nguyen, T. T., Zhang, X., Wu, T., Liu, J., Le, C., Tu, X. M., Knight, R. D., & Jeste, D. V. (2021) · Frontiers in Psychiatry · doi:10.3389/fpsyt.2021.648475 · Cited by 44
“Conversely, probiotic and prebiotic interventions targeting the gut microbiome have been shown to reduce cortisol stress response, cognitive reactivity to sadness, and emotional processing bias (71, 72).”
BackgroundStress and the Microbiota-Gut-Brain Axis
Cryan, J. F. (2016) · The Canadian Journal of Psychiatry · doi:10.1177/0706743716635538 · Cited by 40
“These studies are slowly being translated into research with healthy human volunteers.(22-26) One immediate research goal is to elucidate the mechanisms underpinning the beneficial effects of specific bacterial strains.”
BackgroundMoody microbiome: Challenges and chances
Kuo, P.-H., & Chung, Y.-C. E. (2019) · Journal of the Formosan Medical Association · doi:10.1016/j.jfma.2018.09.004 · Cited by 40
Deleemans, J. M., Chleilat, F., Reimer, R. A., Baydoun, M., Piedalue, K.-A. L., Lowry, D. E., Henning, J., & Carlson, L. E. (2022) · Current Oncology · doi:10.3390/curroncol29050243 · Cited by 38
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Cuomo, A., Maina, G., Rosso, G., Crescenzi, B. B., Bolognesi, S., Muro, A. D., Giordano, N. G., Goracci, A., Neal, S. M., Nitti, M. P., et al. (2018) · Frontiers in Pharmacology · doi:10.3389/fphar.2018.01040 · Cited by 39
“For instance, Bifidobacteria and Lactobacilli can generate of GABA, the Bacillus family can generate dopamine and noradrenaline, and Escherichia can generate noradrenalin and 5-HT.”
BackgroundInfluentialReininghaus, E. Z., Wetzlmair-Kephart, L.-C., Fellendorf, F. T., Platzer, M., Queissner, R., Birner, A., Pilz, R., Hamm, C., Maget, A., Rieger, A., et al. (2018) · Neuropsychobiology · doi:10.1159/000493867 · Cited by 39
The role of microbiota in autism spectrum disorders
Campion, D., Ponzo, P., Alessandria, C., Saracco, G. M., & Balzola, F. A. (2018) · Minerva Gastroenterologica e Dietologica · doi:10.23736/s1121-421x.18.02493-5 · Cited by 40
“lactis decreased cognitive reactivity to sad mood and aggressive thoughts in humans.(83) Furthermore, a functional MRI investigation revealed that administration of a fermented milk product with probiotics resulted in measurable changes in emotional processing in the healthy human brain.”
BackgroundGut microbiota: a target for intervention in obesity
Sehgal, K., & Khanna, S. (2021) · Expert Review of Gastroenterology & Hepatology · doi:10.1080/17474124.2021.1963232 · Cited by 39
The gut-brain axis : dietary, probiotic, and prebiotic interventions on the microbiota
Hyland, N. P., & Stanton, C. (2016) · Cited by 38
Casertano, M., Dekker, M., Valentino, V., De Filippis, F., Fogliano, V., & Ercolini, D. (2024) · Brain, Behavior, and Immunity · doi:10.1016/j.bbi.2024.08.029 · Cited by 35
“Similarly, Steenbergen et al. (2015) in a randomized placebo-controlled study with 20 healthy participants did not find significant changes in mood or anxiety as measured by the Beck Depression Inventory or Beck Anxiety Inventory.”
BackgroundResultLiu, Y., Wu, Z., Cheng, L., Zhang, X., & Yang, H. (2021) · Food & Function · doi:10.1039/d1fo01091c · Cited by 37
The gut microbiota and psychiatric illness
MacQUEEN, G. M., Surette, M. G., & Moayyedi, P. (2017) · Journal of Psychiatry and Neuroscience · doi:10.1503/jpn.170028 · Cited by 37
Parolisi, S., Montanari, C., Borghi, E., Cazzorla, C., Zuvadelli, J., Tosi, M., Barone, R. M. E., Bensi, G., Bonfanti, C., Dionisi‐Vici, C., et al. (2023) · Pharmacological Research · doi:10.1016/j.phrs.2023.106952 · Cited by 36
Potential Beneficial Effects of Probiotics on Human Migraine Headache: A Literature Review
Sun, Y.-H. (2017) · Pain Physician · doi:10.36076/ppj.2017.e255 · Cited by 36
“Recently, a triple-blind, randomized, placebo-controlled clinical trial was carried out to test the effect of 4-week multispecies probiotics on cognitive reactivity to sad mood (15).”
BackgroundForssten, S. D., Ouwehand, A. C., Griffin, S. M., & Patterson, E. (2022) · Nutrients · doi:10.3390/nu14030568 · Cited by 40
Holcomb, M., Marshall, A., Flinn, H., Lozano-Cavazos, M., Soriano, S., Gómez‐Pinilla, F., Treangen, T. J., & Villapol, S. (2025) · Journal of Neuroinflammation · doi:10.1186/s12974-025-03419-1 · Cited by 36
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Neurological and Cognitive Significance of Probiotics: A Holy Grail Deciding Individual Personality
Afzal, M., Mazhar, S. F., Sana, S., Naeem, M. A., Rasool, M. H., Saqalein, M., Nisar, M. A., Rasool, M., Bilal, M., Khan, A. A., et al. (2020) · Future Microbiology · doi:10.2217/fmb-2019-0143 · Cited by 34
Deng, W., Ke, H., Wang, S., Li, Z., Li, S., Lv, P., Li, F., & Chen, Y. (2022) · Behavioural Neurology · doi:10.1155/2022/6711160 · Cited by 36
“A study indicated that probiotics, including Lactococcus, reduce cognitive reactivity to the negative mood via alterations in the activity of brain regions that control the central processing of emotions and sensations [43].”
BackgroundSah, R. K., Nandan, A., Athira, K. V., Prashant, S. K., Sankaran, S., Jose, A., Venkidasamy, B., & Nile, S. H. (2023) · Asian Journal of Psychiatry · doi:10.1016/j.ajp.2023.103861 · Cited by 37
The Local Defender and Functional Mediator: Gut Microbiome
Yang, H., & Duan, Z. (2018) · Digestion · doi:10.1159/000484687 · Cited by 35
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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