Skin Inflammation in Perimenopause: A Probiotic Intervention Proof of Concept Trial

N/ANot Yet RecruitingNCT07341087

King's College London30 enrolled

Overview

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 perimenopause. 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 acne. 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 perimenopause.

Research Question: Can a daily probiotic drink help reduce immune system ageing and improve inflammatory skin conditions, such as acne, in women going through perimenopause? Background Perimenopause is the transition before menopause, usually affecting women aged 40-50. 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 perimenopausal women, who are particularly vulnerable to immune system changes and inflammatory skin conditions. Aims and Hypothesis Aim: To explore whether an oral probiotic Lactobacillus casei Shirota (LcS) can modulate immunological age markers in perimenopausal women with acne. Hypothesis: Consuming 130 ml/day of a low-sugar probiotic (LcS) drink for 8 weeks will significantly reduce inflammation in perimenopausal women with acne compared to 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, 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: Perimenopausal women aged 40-50 years with self-reported or clinically diagnosed acne. * 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 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 Perimenopause 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 perimenopause.

Eligibility

Sex: FEMALEMin age: 40 YearsMax age: 50 Years

Medical Language ↔ Plain English

Inclusion Criteria: 1. Female, aged 40-50 years, in the perimenopausal transition (defined as menstrual cycle irregularity within the past 12 months but not yet 12 months of amenorrhoea). 2. Clinician-diagnosed acne, defined as the presence of acne symptoms (e.g., comedones, papules, pustules, nodules) or a prior formal diagnosis of acne vulgaris by a healthcare professional. 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. History of substance abuse or alcoholism (alcohol intake \>50 units/week) within the last 12 months. 11. Current smokers, or individuals who quit smoking in the last 6-months. 12. Fasting glucose \>7mmol/l (finger prick test at baseline clinic). 13. Active skin infection requiring systemic antibiotics, antivirals, or antifungals within the past 4 weeks. 14. Major gastrointestinal disease (e.g., inflammatory bowel disease, celiac disease, short bowel syndrome) or history of significant gastrointestinal surgery (excluding appendectomy or cholecystectomy). 15. Known immunodeficiency (e.g., HIV, immunosuppressive therapy, systemic corticosteroids \>10 mg/day prednisolone equivalent). 16. History of malignancy or clinically significant non-malignant skin conditions within the past 5 years (except adequately treated basal cell carcinoma). 17. 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). 18. Women with a history of severe psychiatric illness that would limit adherence to study requirements. 19. Current use of probiotics, prebiotics, or antibiotics within 4 weeks prior to baseline. 20. Current use of systemic corticosteroids, or other immunosuppressive/immunomodulatory therapies within the past 3 months. 21. 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. 22. 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). 23. 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). 24. Currently using, or have used, probiotic skincare (e.g., topical creams and serums) within the past 3 months. 25. 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. 26. Currently using, or have used, hormonal contraceptives or treatments known to exacerbate acne, 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. 27. Habitual dietary fibre intake below 10g/day, assessed via the screening questionnaire or dietary assessment, due to the potential impact of low fibre intake on the gut microbiome and study outcomes.

Outcomes

Primary Outcomes

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.

Time frame: 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.

Time frame: Baseline (Week 0) and end of intervention (Week 8).

Secondary Outcomes

Acne-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 such as acne. 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.