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Lost in translation? The potential psychobiotic Lactobacillus rhamnosus (JB-1) fails to modulate stress or cognitive performance in healthy male subjects
Open accessAbstract
Background Preclinical studies have identified certain probiotics as psychobiotics - live microorganisms with a potential mental health benefit. Lactobacillus rhamnosus (JB-1) has been shown to reduce stress-related behaviour, corticosterone release and alter central expression of GABA receptors in an anxious mouse strain. However, it is unclear if this single putative psychobiotic strain has psychotropic activity in humans. Consequently, we aimed to examine if these promising preclinical findings could be translated to healthy human volunteers.Objectives To determine the impact of L. rhamnosus on stress-related behaviours, physiology, inflammatory response, cognitive performance and brain activity patterns in healthy male participants.Methods An 8week, randomized, placebo-controlled, cross-over design was employed. Twenty-nine healthy male volunteers participated. Participants completed self-report stress measures, cognitive assessments and resting electroencephalography (EEG). Plasma IL10, IL1β, IL6, IL8 and TNFα levels and whole blood Toll-like 4 (TLR-4) agonist-induced cytokine release were determined by multiplex ELISA. Salivary cortisol was determined by ELISA and subjective stress measures were assessed before, during and after a socially evaluated cold pressor test (SECPT).Results There was no overall effect of probiotic treatment on measures of mood, anxiety, stress or sleep quality and no significant effect of probiotic over placebo on subjective stress measures, or the HPA response to the SECPT. Visuospatial memory performance, attention switching, rapid visual information processing, emotion recognition and associated EEG measures did not show improvement over placebo. No significant anti-inflammatory effects were seen as assessed by basal and stimulated cytokine levels.Conclusions L. rhamnosus was not superior to placebo in modifying stress-related measures, HPA response, inflammation or cognitive performance in healthy male participants. These findings highlight the challenges associated with moving promising preclinical studies, conducted in an anxious mouse strain, to healthy human participants. Future interventional studies investigating the effect of this psychobiotic in populations with stress-related disorders are required.
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In the citing paper
“Despite promising preclinical findings in animal models, the study found no significant effects of JB-1 on mood, anxiety, sleep quality, or cognitive performance compared to placebo.”
From Psychobiotics in mental health: insights from human clinical trials via the gut-brain axis (2026) · cites this paper as Kelly et al., 2017
In the citing paper
“Additionally, there were no notable changes in inflammatory markers or the HPA stress response.”
From Psychobiotics in mental health: insights from human clinical trials via the gut-brain axis (2026) · cites this paper as Kelly et al., 2017
In the citing paper
“However, in an eight-week crossover design, 29 healthy male volunteers who supplemented with L. rhamnosus exhibited little difference in stress-related measures, HPA axis response, inflammation, or cognitive performance in comparison to placebo [296].”
From International Society of Sports Nutrition Position Stand: Probiotics (2019) · cites this paper as [296]
In the citing paper
“has met with somewhat mixed results in healthy human subjects with strain-specific positive results (Allen et al., 2016;Papalini et al., 2018) and a failure to translate (Kelly et al., 2017).”
From Gut reactions: Breaking down xenobiotic–microbiome interactions (2019) · cites this paper as Kelly et al., 2017
In the citing paper
“However, the probiotic Lactobacillus rhamnosus failed to alter mood, anxiety, and stress-related measures when subjects faced a socially evaluated cold pressor test [392]”
From Anxiety, depression, and the microbiome: A role for gut peptides (2018) · cites this paper as [392]
In the citing paper
“For instance, L. rhamnosus was not found to be superior to placebo in modifying stress, HPA response, inflammation, or cognitive performance, and the authors highlighted the challenges associated with advancing promising preclinical studies in animals to the clinic (487).”
From Signalling cognition: The gut microbiota and hypothalamic-pituitary-adrenal axis (2023) · cites this paper as [487]
In the citing paper
“Notably, the participants were healthy adult males and not patients with stress-related disorders.”
From Signalling cognition: The gut microbiota and hypothalamic-pituitary-adrenal axis (2023) · cites this paper as [487]
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Metadata
- Authors
- Kelly, J. R., Allen, A. P., Temko, A., Hutch, W., Kennedy, P. J., Farid, N., Murphy, E., Boylan, G., Bienenstock, J., Cryan, J. F., Clarke, G., & Dinan, T. G.
- Affiliations
- University College Cork (IE)
- Alimentary Health (Ireland) (IE)
- McMaster University (CA)
- Corresponding author
- Dinan, Timothy G.
- ORCID
- Venue
- Brain, Behavior, and Immunity
- Publisher
- Elsevier BV
- Published
- 2017-03
- Volume
- 61
- Pages
- 50-59
- ISSN
- 0889-1591 (ISSN-L)
- OpenAlex
- W2554850339
- Cited by
- 355
- References
- 75
- Citations by year
- 2026: 24 · 2025: 29 · 2024: 28 · 2023: 47 · 2022: 42 · 2021: 46 · 2020: 36 · 2019: 44 · 2018: 32 · 2017: 26
- FWCI
- 42.85
- Type
- journal article
- Language
- en
- Open access
- green
- hdl.handle.net
- Licence
- Locations
- Brain Behavior and Immunity (publishedVersion)
- PubMed (publishedVersion)
- Arrow@dit (Dublin Institute of Technology) (acceptedVersion)
- Cork Open Research Archive (University College Cork, Ireland) (submittedVersion, cc-by-nc-nd)
- Funders
- SFI (SFI/12/RC/2273)
- HRB (HRA_POR/2011/23, HRA_POR/2012/32, HRA-POR-2-14-647, MYNEWGUT FP7-KBBE-2013-7)
- Topics
- Life Sciences › Agricultural and Biological Sciences › Food Science › Probiotics and Fermented Foods
- Life Sciences › Neuroscience › Behavioral Neuroscience › Stress Responses and Cortisol
- Health Sciences › Medicine › Gastroenterology › Gastrointestinal motility and disorders
- Keywords
- psychobiotics, probiotics, stress, cognitive performance, hypothalamic-pituitary-adrenal axis, salivary cortisol, inflammation, cytokines, TLR4, visuospatial memory, emotion recognition, healthy men
- MeSH terms
- Adult, Attention, Brain, Cognition, Double-Blind Method, Electroencephalography, Humans, Hydrocortisone, Male, Neuropsychological Tests, Saliva, Stress, Psychological, Cytokines, Cross-Over Studies, Probiotics, Lacticaseibacillus rhamnosus, Young Adult, Healthy Volunteers
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