Probiotic Intake and Perimenopausal Psychological Assessments

Official title

The Effects of a Probiotic on Emotional Processing, Cognition, and the Gut Microbiome in Perimenopausal Women

Overview

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.

Detailed description

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.

Interventions

• Dietary supplement Multi-strain probiotic
  A commercially available probiotic known to support gut health and is generally well-tolerated.
• Dietary supplement Placebo
  A microcrystalline cellulose-based capsule.

Primary outcome measures

• Facial Expression Recognition Task (FERT) [Time frame: End of the 60-day intervention]

Secondary outcome measures (11)

• Emotional Categorisation Task [Time frame: End of the 60-day intervention]
• Emotional word recall/recognition task [Time frame: End of the 60-day intervention]
• Digit Span Task [Time frame: End of the 60-day intervention]
• Emotional Go/No-Go (EGNG) [Time frame: Post-intervention (end of 60-day intervention)]
• Probabilistic Reversal Learning (PRL) Task [Time frame: Post-intervention (end of 60-day intervention)]
• N-back Task [Time frame: Post-intervention (end of 60-day intervention)]
• Auditory Verbal Learning Test (AVLT) [Time frame: Post-intervention (end of 60-day intervention)]
• Serum cortisol [Time frame: Baseline and end of 60-day intervention]
• Inflammatory markers [Time frame: Baseline and end of 60-day intervention]
• Serum metabolites [Time frame: Baseline and end of 60-day intervention]
• Gut microbiome composition [Time frame: Baseline and end of 60-day intervention]

Eligibility criteria

Inclusion criteria

• Female at birth
• You are aged 45-60 years and in perimenopause (determined by changes in menstrual bleeding patterns (such as changes in cycle length of 7 days or longer in either direction from what is normal for you), AND vasomotor symptoms (e.g., hot flushes and sweats) AND mild to moderate mood or cognitive disturbances, or joint and muscle pain over the previous 12 months)
• You are willing and able to give informed consent for participation in the study
• You are sufficiently fluent in English to understand and complete tasks
• You are at least 12 months post-natal
• Willing to withhold from having grapefruit juice

Exclusion criteria

• Currently receive or seek treatment for any mental health condition
• Have a BMI >=30 OR <=18.5
• Have lost or gained more than 10% of body weight in a short period (e.g., 6 months), as this can affect mood and cognition
• Currently using hormonal contraception or have used hormonal contraception in the last 6 months
• Have had gender reassignment surgery or gender-affirming hormone therapy
• Had a head injury causing concussion or unconsciousness in the past 6 months
• Participated in other studies that may influence mood, cognition, or gut health in the last three months
• Are currently diagnosed with and/or treated for psychiatric or neurological disorders
• Are on perimenopausal hormone replacement therapy (HRT) (e.g., estrogen, progesterone, testosterone) or other hormone-modulating medications (e.g., GLP-1 agonists, thyroxine replacement), as these can impact mood and cognitive functions
• Currently use statins or have used statins in the last 6 months, as these may impact mood and cognitive functions
• Participated in any other study with the same tasks in the last year
• Currently use medications that influence cognition or mood, such as antidepressants, anxiolytics, antipsychotics, stimulants, mood-stabilizers, or cognitive-enhancing drugs
• Have chronic or severe gastrointestinal diseases (e.g., inflammatory bowel disease, Crohn's disease, celiac disease, or severe acid reflux; treatment with e.g., corticosteroids, antacids), as these conditions and treatments can affect the gut microbiota and immune responses differently from healthy individuals
• Have a compromised immune system
• Currently smoke, vape, or use any other nicotine products
• Have a current diagnosis of cognitive impairment or neurodegenerative disorders (e.g., mild cognitive impairment, dementia), as these conditions could confound cognitive assessments.
• Have severe medical conditions requiring ongoing medication that may independently affect cognition or mood (e.g., diabetes)
• Currently or recently used antibiotics (last 3 months), as antibiotics may alter gut microbiota and interfere with probiotic effects
• Currently or recently used probiotics or prebiotics or consumed fermented products (e.g., kimchi, kombucha, sauerkraut, kefir, etc.) on a regular basis (last 3 months), which might interfere with the study intervention
• Have known allergies or intolerances to probiotics or components in the probiotic supplement.
• Have substance abuse or dependence (e.g., alcohol, recreational drugs) that may affect mood and cognition.
• Have Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (Long COVID)
• Have had a hysterectomy
• Are pregnant or lactating, as hormonal changes associated with these states could confound results.
• Score of 20 or above on PHQ-9 depression questionnaire, indicating severe depression
• Score of >1 on PHQ-9 suicidality item, indicating significant suicidality (as assessed by medical on-site professionals

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Double blind

Primary purpose

Basic science

Study locations

United Kingdom · 1 center

• University of Oxford, Department of Psychiatry — Oxford

Publications

• Weber MT, Rubin LH, Maki PM. Cognition in perimenopause: the effect of transition stage. Menopause. 2013 May;20(5):511-7. doi: 10.1097/gme.0b013e31827655e5. PMID 23615642
• Weber MT, Mapstone M, Staskiewicz J, Maki PM. Reconciling subjective memory complaints with objective memory performance in the menopausal transition. Menopause. 2012 Jul;19(7):735-41. doi: 10.1097/gme.0b013e318241fd22. PMID 22415562
• Ruiz-Gonzalez C, Cardona D, Rueda-Ruzafa L, Rodriguez-Arrastia M, Ropero-Padilla C, Roman P. Cognitive and Emotional Effect of a Multi-species Probiotic Containing Lactobacillus rhamnosus and Bifidobacterium lactis in Healthy Older Adults: A Double-Blind Randomized Placebo-Controlled Crossover Trial. Probiotics Antimicrob Proteins. 2025 Oct;17(5):3525-3537. doi: 10.1007/s12602-024-10315-2. Epub 20 PMID 38935259
• Nikolova VL, Cleare AJ, Young AH, Stone JM. Acceptability, Tolerability, and Estimates of Putative Treatment Effects of Probiotics as Adjunctive Treatment in Patients With Depression: A Randomized Clinical Trial. JAMA Psychiatry. 2023 Aug 1;80(8):842-847. doi: 10.1001/jamapsychiatry.2023.1817. PMID 37314797
• Maki PM, Kornstein SG, Joffe H, Bromberger JT, Freeman EW, Athappilly G, Bobo WV, Rubin LH, Koleva HK, Cohen LS, Soares CN; Board of Trustees for The North American Menopause Society (NAMS) and the Women and Mood Disorders Task Force of the National Network of Depression Centers. Guidelines for the evaluation and treatment of perimenopausal depression: summary and recommendations. Menopause. 2018 PMID 30179986
• Conde DM, Verdade RC, Valadares ALR, Mella LFB, Pedro AO, Costa-Paiva L. Menopause and cognitive impairment: A narrative review of current knowledge. World J Psychiatry. 2021 Aug 19;11(8):412-428. doi: 10.5498/wjp.v11.i8.412. eCollection 2021 Aug 19. PMID 34513605
• Bromberger JT, Epperson CN. Depression During and After the Perimenopause: Impact of Hormones, Genetics, and Environmental Determinants of Disease. Obstet Gynecol Clin North Am. 2018 Dec;45(4):663-678. doi: 10.1016/j.ogc.2018.07.007. Epub 2018 Oct 25. PMID 30401549
• Berent-Spillson A, Marsh C, Persad C, Randolph J, Zubieta JK, Smith Y. Metabolic and hormone influences on emotion processing during menopause. Psychoneuroendocrinology. 2017 Feb;76:218-225. doi: 10.1016/j.psyneuen.2016.08.026. Epub 2016 Sep 5. PMID 27622993

Identifiers

NCT: NCT07590999 · PIPPA Study (735575)

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗