Effect of Probiotic on Cognitive Function

Overview

The goal of this clinical trial is to learn if daily single-strain probiotic supplementation (Lactobacillus plantarum) works to improve cognitive function and depressive symptoms in Egyptian women aged 50-64 years with mild depression. It will also learn about its effects on systemic inflammation and autonomic nervous system function via the gut-brain axis The main questions it aims to answer are: Does a 12-week probiotic supplementation improve cognitive function (measured by MoCA-B) compared to a placebo? Does it reduce the severity of depressive symptoms (measured by BDI-II)? Does it reduce systemic inflammation (measured by hs-CRP levels in the blood)? Does it enhance autonomic nervous system function (measured by Heart Rate Variability - HRV via a smartphone app)? Researchers will compare the probiotic capsule (Lactobacillus plantarum, 10 billion CFU) to a placebo (a look-alike capsule containing starch) to see if the probiotic works better than placebo. Participants will: Take one probiotic or placebo capsule orally every morning with breakfast for 12 weeks. Visit the Family Medicine outpatient clinic at baseline and at 12 weeks for cognitive and psychological tests, HRV measurements, and blood tests. Receive weekly follow-up messages on WhatsApp to monitor adherence and report any dietary changes or potential side effects.

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).