Skin Inflammation in (Peri)Menopause: A Probiotic Intervention Proof of Concept Trial (SIPPI)

Skin Inflammation in (Peri)Menopause: A Probiotic Intervention Proof of Concept Trial (SIPPI)

This study will explore whether a daily probiotic drink containing Lactobacillus casei Shirota (LcS) can help improve immune function and reduce inflammation in women going through the menopausal transition. Hormonal changes during this stage of life can affect the immune system, gut health, and skin, sometimes leading to increased inflammation or conditions such as eczema, acne or rosacea.

Participants will consume either a low-sugar LcS probiotic drink or a skimmed milk control drink every day for eight weeks. The study will assess markers of immune ageing, inflammation, skin health, wellbeing, and hormone levels. The results will help determine whether a safe, non-hormonal probiotic approach may support immune and skin health during the menopausal transition.

Study Overview

• Status: Recruiting
• Conditions: Inflammation; Menopause; Eczema; Rosacea; Immunosenescence; Acne; Skin Inflammation; Skin Health
• Intervention / Treatment: Dietary supplement: Lactobacillus casei Shirota (LcS) Probiotic Drink; Other: Skimmed Milk Control Drink

Detailed Description

Research Question: Can a daily probiotic drink help reduce immune system ageing and improve inflammatory skin conditions in women going through menopause?

Background

The menopausal transition usually affects women aged 40-60. During this time, hormone levels, especially oestrogen, fluctuate and gradually decline. These changes can affect the immune system, making it more prone to inflammation and less effective over time.

Lower oestrogen can also affect the skin, leading to dryness, irritation, or acne. It can change the balance of bacteria in the gut and on the skin, which may worsen inflammation and overall health.

While hormone replacement therapy can help some symptoms, it is not suitable for all women. Currently, there is little research on safe, non-hormonal ways to support the gut, immune system, and skin together. One promising approach is using probiotics - beneficial bacteria that can improve gut health and reduce inflammation.

Lactobacillus casei Shirota (LcS) is a probiotic that has shown anti-inflammatory and immune-supporting effects in other adults. However, it has not been studied in menopausal women, who are particularly vulnerable to immune system changes and inflammatory skin conditions.

Aims and Hypothesis

Aim: To investigate whether the oral probiotic Lactobacillus casei Shirota (LcS) can influence markers of immunological ageing in women undergoing the menopausal transition who are experiencing skin conditions.

Hypothesis: Consuming 130 ml/day of a low-sugar probiotic (LcS) drink for 8 weeks will significantly reduce inflammation in women undergoing the menopausal transition with skin conditions, compared with a 130 ml/day skimmed milk control.

Objectives

Primary Objective: To determine if daily LcS consumption can improve immune function, measured using a composite "immune age" score (IMM-AGE) that reflects overall immune health and inflammation.

Secondary Objectives:

• To look at self-reported skin health, immune status, general wellbeing, and gut health.
• To assess skin inflammation and signs of ageing through clinician assessments and images.
• To measure hormone levels (oestrogen and FSH).

Study design

• Trial Design: Randomised, parallel, open-label, proof of concept trial, with an 8-week intervention and blinded outcome assessment.
• Participants: Peri- and postmenopausal women aged 40-60 years with self-reported or clinically diagnosed non-infectious, non-autoimmune skin conditions.
• Intervention: Daily 130 ml low-sugar LcS probiotic drink for 8 weeks.
• Comparison: Daily 130 ml skimmed milk (control) for 8 weeks.

Measurements:

• Immune function (IMM-AGE)
• Blood markers of inflammation (cytokines including CD14, IFN-α, IFN-γ, IL1Ra, IL-6, IL-10, TNF-α, GM-CSF, IFN-β, IL1β, IL-4, IL-8, IL-17) and hormones (oestrogen and follicle stimulating hormone [FSH] levels)
• Skin health and ageing
• Self-reported wellbeing, immune status, and gut health

Stool and skin samples will also be collected for future research, but these will not be analysed in this trial.

5. Why This Study Matters

The menopausal transition is a time of rapid biological change that can affect immunity and skin health. This trial will test a safe, non-hormonal approach to support the immune system, reduce inflammation, and improve skin health in midlife women. The results will help guide future research and may inform practical strategies to improve wellbeing during menopause.

• Study Type: Interventional
• Enrollment (Estimated): 30
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Prof. Wendy Hall; Phone Number: +44 (0)20 7848 4197; Email: wendy.hall@kcl.ac.uk
• Study Contact Backup: Name: Andrea Du Preez, PhD; Email: andrea.du_preez@kcl.ac.uk

Study Locations

• United Kingdom
  • London
    • London, London, United Kingdom, SE1 9NH
      • Recruiting
      • Metabolic Research Unit, 4th Floor (Corridor A), Franklin-Wilkins Building, KCL.
      • Contact: Prof. Wendy Hall; Phone Number: +44 (0)20 7848 4197; Email: wendy.hall@kcl.ac.uk
      • Contact: Andrea Du Preez, PhD; Email: andrea.du_preez@kcl.ac.uk
      • Principal Investigator: Wendy Hall
      • Sub-Investigator: Andrea Du Preez
      • Sub-Investigator: Anya Klarner
      • Sub-Investigator: Bochen Li

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Female, aged 40-60 years.
2. Self-reported or clinician-diagnosed non-infectious, non-autoimmune inflammatory skin condition affecting the face (e.g., rosacea, acne, eczema).
3. Willing and able to consume a daily oral intervention (2x 65 ml probiotic drinks or skimmed milk) for 8 weeks.
4. Willing and able to provide sufficient blood, skin and stool samples at baseline and end-of-study (Week 8). Participants unable to provide adequate blood sample volumes will not be able to start the intervention.
5. Willing and able to provide a photograph of the facial area, with all images anonymised for study purposes.
6. Able to comply with study procedures, including attending clinic visits at KCL.
7. Have access to a refrigerator at home and be able to store the study product(s) safely after collection (i.e., travel time allows safe storage).
8. Capable of providing written informed consent.
9. Have sufficient proficiency in English to complete study questionnaires and assessments.

Exclusion Criteria:

1. Inability or unwillingness to provide informed consent.
2. Inability or unwillingness to comply with study protocol requirements (e.g., clinic visits, sample provision, daily consumption of study drink)
3. Unwilling to record dietary intakes using handwritten diet diaries
4. Not fluent in the English language
5. Is planning on international travel during the study period
6. Current participation in another interventional clinical trial or having received an investigational/pharmaceutical product within the past 3 months.
7. Known allergy or intolerance to dairy products, skimmed milk, or probiotic drinks containing Lactobacillus species.
8. Currently pregnant, currently breastfeeding or planning to become pregnant in the next 4 months.
9. BMI <18.5kg/m2 or > 35kg/m2.
10. Unintentional weight loss greater than 4 kg in the 3 months prior to enrolment.
11. History of substance abuse or alcoholism (alcohol intake >50 units/week) within the last 12 months.
12. Current smokers, or individuals who quit smoking in the last 6-months.
13. Fasting glucose >7mmol/l (finger prick test at baseline clinic).
14. Active skin infection requiring systemic antibiotics, antivirals, or antifungals within the past 4 weeks.
15. Major gastrointestinal disease (e.g., inflammatory bowel disease, celiac disease, short bowel syndrome) or history of significant gastrointestinal surgery (excluding appendectomy or cholecystectomy).
16. Known immunodeficiency (e.g., HIV, immunosuppressive therapy, systemic corticosteroids >10 mg/day prednisolone equivalent).
17. History of malignancy or clinically significant non-malignant skin conditions within the past 5 years (except adequately treated basal cell carcinoma).
18. Serious medical conditions that, in the opinion of the investigator, would compromise safety or interfere with study outcomes (e.g., uncontrolled diabetes, advanced cardiovascular, hepatic, or renal disease, active cancer, autoimmune conditions).
19. Women with a history of severe psychiatric illness that would limit adherence to study requirements.
20. Current use of probiotics, prebiotics, or antibiotics within 4 weeks prior to baseline.
21. Current use of systemic corticosteroids, or other immunosuppressive/immunomodulatory therapies within the past 3 months.
22. Currently receiving, or having received, phototherapy (e.g., UVB, PUVA, laser/light-based treatments, including at home treatments) for any skin condition within the past 3 months.
23. Currently receiving, or having received, systemic dermatology treatments likely to affect skin inflammation or immune response within the past 3 months (e.g., isotretinoin, methotrexate, cyclosporine, biologics such as TNF, IL-17, IL-23 or IL-4/IL-13 inhibitors).
24. Currently receiving, or having received, topical treatments likely to significantly alter skin inflammation within the past 3 months (e.g., high-potency topical corticosteroids, topical calcineurin inhibitors such as tacrolimus or pimecrolimus, topical retinoids, or photodynamic therapy).
25. Currently using, or have used, probiotic skincare (e.g., topical creams and serums) within the past 3 months.
26. Currently receiving, have undergone, or plan to undergo cosmetic skin procedures (e.g., chemical peels, laser therapy, dermal fillers, microneedling) within the 3 months prior to, or within 3 months after the first (baseline) visit.
27. Currently using, or have used, hormonal contraceptives or treatments known to exacerbate skin conditions, including Mirena (levonorgestrel-releasing intrauterine system), oral progesterone-only contraceptives (e.g., mini-pill), and synthetic progestogens (e.g., norethisterone) within the past 3 months.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Arm 1 - Probiotic (LcS); Daily 130 ml low-sugar Lactobacillus casei Shirota (LcS) drink for 8 weeks.	Dietary supplement: Lactobacillus casei Shirota (LcS) Probiotic Drink; Daily intake of 130 ml low-sugar fermented milk drink containing Lactobacillus casei Shirota for 8 weeks.
Active Comparator: Arm 2 - Control; Daily 130 ml skimmed milk drink for 8 weeks.	Other: Skimmed Milk Control Drink; Daily intake of 130 ml skimmed milk for 8 weeks.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Immunological age (IMM-AGE) composite scores	A subset of eight immune cell types-total T cells, naïve CD4 T cells, effector memory CD4 T cells, effector memory CD8 T cells, EMRA CD8 T cells, CD28- CD8 T cells, CD57⁺ CD8 T cells, and regulatory T cells-will be used to generate a composite score ranging from 0 to 1 that reflects the degree of immune ageing. Higher scores indicate more advanced immune ageing and worse outcomes.	Baseline (Week 0) and end of intervention (Week 8).
Serum inflammaging markers	Serum cytokines including CD14, IFN-α, IFN-γ, IL-1Ra, IL-6, IL-10, TNF-α, GM-CSF, IFN-β, IL-1β, IL-4, IL-8, and IL-17.	Baseline (Week 0) and end of intervention (Week 8).

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
General wellbeing	Wellbeing will be assessed using the World Health Organization Five Well-Being Index (WHO-5), a validated, self-administered questionnaire measuring current mental wellbeing. The WHO-5 consists of five items, each scored from 0 ("At no time") to 5 ("All of the time"). Raw total scores range from 0 to 25, with higher scores indicating better wellbeing. For standardised reporting, the total score may be transformed to a scale from 0 to 100, where 0 represents the worst possible wellbeing and 100 represents the best possible wellbeing.	Baseline (Week 0) and Endpoint (Week 8)
Menopause symptoms	Menopausal symptoms will be assessed using the Menoscale, a questionnaire consisting of 20 questions about menopausal symptoms. For each symptom, participants rate the extent to which it impacts their life using a scale from 0 ("Not at all") to 5 ("Extremely"). Responses are summed to generate a total score ranging from 0 to 100. Higher scores indicate a greater burden of menopausal symptoms and a worse impact on quality of life.	Baseline (Week 0), Midpoint (Week 4) and Endpoint (Week 8)
Anxiety symptoms	Anxiety symptoms will be assessed using the Generalized Anxiety Disorder 7-item scale (GAD-7), a validated, self-administered questionnaire. The GAD-7 consists of seven items, each scored from 0 ("Not at all") to 3 ("Nearly every day"). Total scores range from 0 to 21, with higher scores indicating more severe anxiety symptoms and worse outcomes.	Baseline (Week 0), Midpoint (Week 4) and Endpoint (Week 8)
Depressive symptoms	Depressive symptoms will be assessed using the Patient Health Questionnaire-9 (PHQ-9), a validated, self-administered questionnaire. The PHQ-9 consists of nine items, each scored from 0 ("Not at all") to 3 ("Nearly every day"). Total scores range from 0 to 27, with higher scores indicating more severe depressive symptoms and worse outcomes.	Baseline (Week 0), Midpoint (Week 4) and Endpoint (Week 8)
Gastrointestinal symptoms	Gastrointestinal symptoms will be assessed using the Gastrointestinal Symptom Rating Scale (GSRS), a validated, self-administered questionnaire. The GSRS consists of multiple items assessing gastrointestinal symptoms, each scored on a Likert scale from 1 to 7. Item scores are averaged to generate a total score ranging from 1 to 7, where 1 represents no discomfort and 7 represents very severe discomfort. Higher scores indicate worse gastrointestinal symptom severity and worse outcomes.	Baseline (Week 0), Midpoint (Week 4) and Endpoint (Week 8)
Stool consistency	Stool form will be assessed using the Bristol Stool Form Scale (BSFS), a validated visual and descriptive scale used to classify stool consistency. The BSFS categorises stool form into seven types, ranging from Type 1 (separate hard lumps, indicating severe constipation) to Type 7 (watery, no solid pieces, indicating severe diarrhoea). Lower scores indicate harder stool consistency, and higher scores indicate looser stool consistency and worse gastrointestinal outcomes.	Baseline (Week 0) and Endpoint (Week 8)
Body weight	Body weight will be measured in kilograms (kg) using a calibrated scale. Changes in body weight will be assessed over time, with higher values indicating greater body weight.	Baseline (Week 0), Midpoint (Week 4) and Endpoint (Week 8)
Body Mass Index (BMI)	Body mass index (BMI) will be calculated as weight in kilograms divided by height in meters squared (kg/m²). Higher BMI values indicate greater body mass relative to height.	Baseline (Week 0), Midpoint (Week 4), Endpoint (Week 8)
Body fat percentage	Body fat percentage will be measured using a bioelectrical impedance analysis (BIA) scale and reported as a percentage (%). Higher values indicate a greater proportion of body fat.	Baseline (Week 0), Midpoint (Week 4), Endpoint (Week 8)
Waist circumference	Waist circumference will be measured in centimetres (cm) using a standardised tape measure at the midpoint between the lowest rib and the iliac crest. Higher values indicate greater central adiposity.	Baseline (Week 0), Midpoint (Week 4), Endpoint (Week 8)
Hip circumference	Hip circumference will be measured in centimetres (cm) using a standardised tape measure at the level of the widest portion of the buttocks. Higher values indicate greater hip circumference.	Baseline (Week 0), Midpoint (Week 4), Endpoint (Week 8)
Systolic Blood Pressure	Systolic blood pressure will be measured in millimetres of mercury (mmHg) using a calibrated sphygmomanometer. Higher values indicate higher systolic blood pressure and worse cardiovascular outcomes.	Baseline (Week 0), Midpoint (Week 4), Endpoint (Week 8)
Diastolic blood pressure	Diastolic blood pressure will be measured in millimetres of mercury (mmHg) using a calibrated sphygmomanometer. Higher values indicate higher diastolic blood pressure and worse cardiovascular outcomes.	Baseline (Week 0), Midpoint (Week 4), Endpoint (Week 8)
Skin Ageing	Signs of skin ageing will be assessed by a blinded clinician using standardised photographic images and the Griffiths Photonumeric Scale. The Griffiths scale is a validated 9-point photonumeric grading system used to assess the severity of facial photoaging features, including wrinkling, pigmentation changes, and overall skin texture. Scores range from 0 (no photoaging) to 8 (severe photoaging), with higher scores indicating more advanced skin ageing and worse outcomes.	Baseline (Week 0), Midpoint (Week 4) and Endpoint (Week 8)
Immune status	The Immune Status Questionnaire (ISQ) will be used to assess participants' perceived immune functioning. The ISQ is a validated patient-reported outcome measure consisting of seven items that evaluate the frequency of common immune-related symptoms, including common colds, diarrhoea, sudden high fever, headache, muscle and joint pain, skin problems, and coughing. Each item is rated on a 5-point Likert scale (0 = never to 4 = frequently). Item scores are summed and transformed to a total score ranging from 0 to 10, with higher scores indicating better perceived immune status (fewer symptoms) and lower scores indicating poorer immune functioning.	Baseline (Week 0) and Endpoint (Week 8)
Skin-related quality of life	Health-related quality of life will be assessed using the Dermatology Life Quality Index (DLQI), a validated, self-administered questionnaire for individuals with skin conditions. The DLQI consists of 10 items, each scored from 0 ("Not at all" or "Not relevant") to 3 ("Very much"). Total scores range from 0 to 30, where 0 represents no impact on quality of life and 30 represents an extremely large negative impact. Higher scores indicate worse health-related quality of life outcomes.	Baseline (Week 0), Midpoint (Week 4) and Endpoint (Week 8)
Skin condition severity - participant perception	The Patient Global Assessment (PtGA) will be used to assess the participant's overall perception of the severity of their skin condition. The PtGA is a patient-reported outcome measure scored on a numeric scale ranging from 0 to 10, where 0 represents no symptoms and 10 represents the worst possible symptom severity imaginable. Higher scores indicate worse skin condition severity and worse outcomes.	Baseline (Week 0), Midpoint (Week 4) and Endpoint (Week 8)
Skin condition severity - clinician rated (measure 1)	For all skin conditions, severity will be assessed by a blinded clinician using standardised photographic images and the Investigator Global Assessment (IGA), scored from 0 (clear) to 4 (severe). Higher scores indicate worse outcomes.	Baseline (Week 0), Midpoint (Week 4) and Endpoint (Week 8)
Acne severity - clinician rated (measure 2 - acne only)	For those presenting with acne only, severity will be assessed by a blinded clinician using standardised photographic images and the Leeds Acne Grading System, with scores ranging from 0 to 10. Higher scores indicate more severe acne and worse outcomes.	Baseline (Week 0), Midpoint (Week 4) and Endpoint (Week 8)

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Fasting glucose levels	Fasting blood glucose levels will be measured using a finger-prick capillary blood test after an overnight fast. This will be used to screen for (and exclude those with) hyperglycaemia (>7 mmol/L).	Baseline (Week 0)
Hormone levels	Follicle Stimulating Hormone (FSH) and oestrogen levels - to control for heterogeneity in menopausal status	Baseline (Week 0)
Ovarian reserve	The Stages of Reproductive Aging Workshop +10 (STRAW+10) criteria will be used to classify reproductive aging stage and to determine ovarian reserve and menopausal status based on menstrual cycle characteristics and relevant clinical information. Classification will be performed according to established STRAW+10 definitions.	Baseline (Week 0)

Collaborators and Investigators

• Sponsor: King's College London
• Collaborators: Yakult (UK & Ireland) Ltd
• Investigators: Principal Investigator: Wendy Hall, King's College London; Study Director: Andrea Du Preez, King's College London

Study record dates

Study Major Dates

• Study Start (Actual): April 28, 2026
• Primary Completion (Estimated): November 1, 2027
• Study Completion (Estimated): November 1, 2027

Study Registration Dates

• First Submitted: December 11, 2025
• First Submitted That Met QC Criteria: January 6, 2026
• First Posted (Actual): January 14, 2026

Study Record Updates

• Last Update Posted (Actual): May 8, 2026
• Last Update Submitted That Met QC Criteria: May 5, 2026
• Last Verified: December 1, 2025

More Information

Terms related to this study

• Keywords: Probiotics; Lactobacillus casei Shirota; Skin health; Immune ageing; Gut-skin axis; Menopausal transition
• Additional Relevant MeSH Terms: Pathologic Processes; Skin Diseases; Skin Diseases, Eczematous; Acneiform Eruptions; Sebaceous Gland Diseases; Pathological Conditions, Signs and Symptoms; Skin and Connective Tissue Diseases; Inflammation; Dermatitis; Eczema; Acne Vulgaris; Rosacea
• Other Study ID Numbers: HR-25/26-52828; BB/X010821/1 (Other Grant/Funding Number: BBSRC-iNutriLife and Yakult)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: Individual participant data will not be shared outside the study team because our ethics approval and participant consent do not permit external sharing of de-identified data.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No