Effect of Probiotic on Cognitive Function

Depression poses a significant global public health challenge, with women being two to three times more likely than men to develop the condition. Emerging evidence highlights a bidirectional relationship between depression, cognitive impairment, and the gut microbiota via the gut-brain axis. Dysbiosis in gut microbiota can contribute to systemic inflammation, impaired neurogenesis, and psychiatric disorders. Specific strains such as Lactobacillus plantarum have shown potential in modulating gut-brain communication, reducing inflammation, and improving neurocognitive and psychological outcomes.

This triple-blind, randomized, placebo-controlled trial aims to evaluate the efficacy of a 12-week intervention with a single-strain probiotic (Lactobacillus plantarum, 10 billion CFU daily) compared to a placebo in Egyptian women aged 50-64 years presenting with mild depressive symptoms.

Study Procedures and Flow:

Initial Screening Visit: Potential participants recruited from the Family Medicine outpatient clinics at Kasr Al-Ainy Teaching Hospitals will undergo screening. Eligibility will be confirmed by taking a comprehensive medical/psychiatric history, reviewing concomitant medications/supplements, and evaluating depressive symptoms using the Arabic validated Beck Depression Inventory-II (BDI-II, score 14-19). Eligible participants will provide written informed consent.

Baseline Assessment (Week 0): Enrolled participants will undergo baseline evaluations including:

Socio-demographic status assessment. Anthropometric measurements (weight, height, BMI). Cognitive assessment using the Arabic version of the Montreal Cognitive Assessment - Basic (MoCA-B).

Autonomic nervous system function evaluation via short-term (5-minute) resting Heart Rate Variability (HRV) measured using a smartphone-based photoplethysmography application (Welltory) under standardized conditions.

Fasting venous blood sample collection for high-sensitivity C-reactive protein (hs-CRP) level measurement.

Randomization and Intervention Phase (Weeks 1-12): Participants will be randomly allocated in a 1:1 ratio to either the probiotic or placebo group using a computer-generated permuted block design. Both intervention (probiotic) and control (placebo) capsules are identical in appearance, size, color, and packaging. Participants, assessors, and the data analyst/statistician will remain blinded throughout the study. Participants will take one capsule daily with breakfast for 12 weeks. Adherence will be monitored through weekly messaging and monthly capsule counts during study visits.

Post-Intervention Assessment (Week 12): At the end of the 12-week intervention period, participants will undergo repeat outcome assessments identical to baseline (MoCA-B, BDI-II, HRV, and fasting serum hs-CRP).

Inclusion criteria

Females, aged 50-64 years

• Presence of mild depressive symptoms, defined as a Beck Depression inventory II (BDI-II) total score between 14 and 19 (inclusive) at the screening visit.
• Ability to give informed consent

Exclusion criteria

• Moderate and severe depression (BDI-II score > 19) or active suicidal ideation (assessed by clinical interview).
• Diagnosis of bipolar disorder, schizophrenia, or other major psychotic disorder.

Current use of antidepressants, antipsychotics, mood stabilizers, or regular anxiolytics

• Regular consumption of probiotics, prebiotics, or synbiotic supplements within the past 4 weeks.
• Use of antibiotics or antifungals within the past 4weeks.
• Known diagnosis of inflammatory bowel disease, celiac disease, or active irritable bowel syndrome with severe symptoms.
• History of significant cardiovascular disease (e.g., atrial fibrillation, heart failure, recent MI), uncontrolled hypertension, or type 1 diabetes.
• Current use of systemic hormone replacement therapy within the last 3 months.Research Template 6 Final Version: Jan 2024
• Known allergy to any component of the probiotic or placebo.
• Severe systemic illness (e.g., uncontrolled diabetes, malignancy, severe hepatic, renal disease or auto-immune diseases).
• CRP more than 10