Recent evidence suggests multi-strain probiotics containing Lactobacillus rhamnosus and Bifidobacterium longum have been found to enhance emotional processing and reduce salience to negative cues in studies involving people with mood disorders, as well as improve cognitive functions, such as memory and concentration, in healthy participants. By administering computer-based tasks, questionnaires and checking biological measures (cortisol, immune markers, blood metabolites, gut microbiota) using blood and faecal samples, this experimental medicine study aims to investigate whether a probiotic supplement has an effect on emotional processing and cognition in perimenopausal women. We also aim to study changes in gut bacteria from stool samples before and after taking the supplement to see if any microbiome changes are associated with any effects in emotional processing, cognitive function, and biological markers.
Perimenopause, the transition period leading up to menopause, involves fluctuating levels of oestrogen and other hormones, contributing to a variety of physical and metabolic changes. It is also a period associated with an increased risk of depression and a decline in cognitive functioning. When compared to the pre-perimenopausal period, perimenopausal women are two to five times more susceptible to experiencing depressive episodes. Cognitive decline, including memory and concentration issues, is also prevalent, with an estimated 44-62% of individuals reporting challenges with memory. Research often highlights the role of the gut-brain axis, where the gut microbiota influences cognitive function and emotional processing via neurotransmitters, inflammatory markers, and stress response pathways. Recent evidence suggests that multi-strain probiotics containing Lactobacillus rhamnosus and Bifidobacterium longum enhance emotional processing and reduce salience to negative cues in studies involving people with mood disorders, as well as improving cognitive functions, such as memory and concentration, in healthy participants. One 8-week study also found preliminary evidence supporting the potential of probiotics as a safe and effective adjunctive treatment for major depressive disorder in individuals with incomplete responses to antidepressant medication. Given these observed benefits, the investigation into the effects of multi-strain probiotics to address emotional processing and cognitive disturbances and perturbations in a perimenopausal population is lacking. With the increasing demand for natural, non-pharmacological therapeutic interventions to manage perimenopausal symptoms, this project could provide valuable evidence supporting the use of probiotics as a beneficial adjunct therapy in perimenopausal health management. The current proposal will assess the effects of a commercial probiotic on emotional processing and cognitive function in perimenopausal women, alongside changes in gut microbial composition that may mediate any observed metabolic changes and effects on inflammatory markers and metabolites. This is an important next step in elucidating the role probiotics may play in perimenopause and in generating data to guide future clinical applications of probiotics in managing perimenopausal symptoms.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
BASIC_SCIENCE
Masking
DOUBLE
Enrollment
106
A commercially available probiotic known to support gut health and is generally well-tolerated.
A microcrystalline cellulose-based capsule.
University of Oxford, Department of Psychiatry
Oxford, England, United Kingdom
RECRUITINGFacial Expression Recognition Task (FERT)
Accuracy, reaction time and misclassifications on the FERT compared between probiotic and placebo groups.
Time frame: End of the 60-day intervention
Emotional Categorisation Task
Accuracy and reaction time performance on emotional word categorization task compared between probiotic and placebo groups.
Time frame: End of the 60-day intervention
Emotional word recall/recognition task
Performance on emotional word recall (hits and false alarms) and recogntion (hits, false alarms and reaction time) compared between probiotic and placebo groups
Time frame: End of the 60-day intervention
Digit Span Task
Maximum span length compared between probiotic and placebo groups
Time frame: End of the 60-day intervention
Emotional Go/No-Go (EGNG)
Cognitive control and inhibitory control assessed using the EGNG task, including commission errors, omission errors, and reaction time to emotionally valenced stimuli. Performance will be compared between probiotic and placebo groups at post-intervention.
Time frame: Post-intervention (end of 60-day intervention)
Probabilistic Reversal Learning (PRL) Task
Cognitive flexibility and reward-based learning assessed using the PRL task, including measures such as response accuracy, reversal errors, and sensitivity to reward and punishment. Performance will be compared between probiotic and placebo groups at post-intervention.
Time frame: Post-intervention (end of 60-day intervention)
N-back Task
Working memory performance assessed using the n-back task, including accuracy and reaction time across task conditions. Performance will be compared between probiotic and placebo groups at post-intervention.
Time frame: Post-intervention (end of 60-day intervention)
Auditory Verbal Learning Test (AVLT)
Verbal learning and memory assessed using the AVLT, including measures of immediate recall, delayed recall, and recognition memory. Performance will be compared between probiotic and placebo groups at post-intervention.
Time frame: Post-intervention (end of 60-day intervention)
Serum cortisol
Serum cortisol concentration assessed using ELISA compared between the placebo and probiotic groups
Time frame: Baseline and end of 60-day intervention
Inflammatory markers
Inflammatory marker concentrations (CRP, IL-1b, TNF-alpha, IL-6) assessed using ELISA compared between placebo and probiotic groups
Time frame: Baseline and end of 60-day intervention
Serum metabolites
Serum metabolite profiles assessed using ELISA compared between placebo and probiotic groups
Time frame: Baseline and end of 60-day intervention
Gut microbiome composition
Gut microbiome composition assessed using stool samples, including measures of alpha diversity, beta diversity, and relative abundance of microbial taxa, compared between placebo and probiotic groups.
Time frame: Baseline and end of 60-day intervention
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