Lactobacillus-containing Cultured Milk Drink Alleviates Depression Score Among Adults With Irritable Bowel Syndrome

Study Overview
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Brief Summary
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Irritable bowel syndrome (IBS) is frequently associated with any form of psychiatric comorbidities including subthreshold or subclinical depression. Modification of gut ecology with probiotics has implicitly improved IBS and depressive symptoms. However, the efficacy of probiotics on IBS with existing subthreshold depression remain elusive. Therefore, the aim of this study is to evaluate the effects of lactobacillus-containing cultured milk drink on depression scores in adults diagnosed with IBS.

Detailed Description
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A total of 140 subjects who fulfilled Rome IV criteria for IBS will be recruited from a tertiary medical centre and among public volunteers. The depression status and categories will be assessed using the Centre Epidemiologic Studies Depression Scale Revised questionnaire (CESD-R): normal mood (score<16), or subthreshold depression (score>16). The subjects are randomised and blinded into four groups: Group A (Normal mood with placebo, n=35), Group B (Normal mood with probiotics, n=35), Group C (Subthreshold depression with placebo, n=35) and Group D (Subthreshold depression with probiotics, n=35). The subjects will be instructed to consume two bottles of cultured milk drink daily for 12 weeks. The probiotic cultured milk drinks contained 10^9 cfu L. CASEI-01 and LA-5. The severity of depression will be measured using Patient Health Questionnaire (PHQ-9) at pre- and post-12-week intervention. Secondary outcome on IBS symptoms severity will be assessed with IBS Symptoms Severity Score (IBS-SSS) and IBS Quality of Life (IBS-QOL).

Official Title
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The Efficacy of Lactobacillus-containing Cultured Milk Drink in Alleviating Subthreshold Depression Among Adults With Irritable Bowel Syndrome

Conditions
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Irritable Bowel Syndrome With Subthreshold Depression

Intervention / Treatment
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* Dietary Supplement: Lactobacillus containing cultured milk drink
* Dietary Supplement: Placebo cultured milk drink


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Aged 18 to 65 years old, Meet ROME IV criteria for irritable bowel syndrome, Consented to participate in the study. Exclusion Criteria: Lactose intolerance, Gastrointestinal disorders such as inflammatory bowel diseases, liver diseases, pancreatic diseases or malignancies, Any neurological diseases or malignancies, Pregnant and lactating mothers, Any metabolic diseases such as hypertension, hypercholesterolaemia, diabetes mellitus, hyper- and hypothyroidism. Known psychiatric diagnoses or/and consume psychotropic drugs, Ongoing electroconvulsive therapy (ECT), Consumption of antibiotics, probiotics, prebiotics, symbiotics products, laxatives, antispasmodics, and/or anticholinergics who refuse to consent for participation.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: This is a randomized and parallel study involving patients with IBS who attended gastroenterology clinics at Universiti Kebangsaan Malaysia Medical Center (UKMMC). The recruited subjects will be categorized according to their CESD-R scores and randomly allocated into receiving either placebo or probiotic-containing cultured milk drink for 12 weeks.
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Irritable bowel syndrome with normal mood receiving placebo<br>A total of 35 patients diagnosed with IBS as per Rome IV criteria who scored CESD-R less than 16 will be supplemented with placebo drinks. | Dietary Supplement: Placebo cultured milk drink<br>* The placebo prepared was identical to the probiotic-containing product in terms of color, taste and packaging. However, there is no trace of live microorganism in this product.<br>|
| Active Comparator: Irritable bowel syndrome with normal mood receiving probiotics<br>A total of 35 patients diagnosed with IBS as per Rome IV criteria who scored CESD-R less than 16 will be given lactobacillus-containing cultured milk drinks. | Dietary Supplement: Lactobacillus containing cultured milk drink<br>* Each bottle of 125ml cultured milk drink contains a billion colony forming unit (CFU) Lactobacillus acidophillus (LA-5) and Lactobacillus paracasei (L. CASEI-01). Each patient will be given 2 bottles to consume daily for a period of 12 weeks.<br>|
| Placebo Comparator: Irritable bowel syndrome with subthreshold depression receiving placebo<br>A total of 35 patients diagnosed with IBS as per Rome IV criteria who scored CESD-R of 16 or above will be supplemented with placebo drinks. | Dietary Supplement: Placebo cultured milk drink<br>* The placebo prepared was identical to the probiotic-containing product in terms of color, taste and packaging. However, there is no trace of live microorganism in this product.<br>|
| Experimental: Irritable bowel syndrome with subthreshold depression receiving probiotics<br>A total of 35 patients diagnosed with IBS as per Rome IV criteria who scored CESD-R of 16 or above will be given lactobacillus-containing cultured milk drinks. | Dietary Supplement: Lactobacillus containing cultured milk drink<br>* Each bottle of 125ml cultured milk drink contains a billion colony forming unit (CFU) Lactobacillus acidophillus (LA-5) and Lactobacillus paracasei (L. CASEI-01). Each patient will be given 2 bottles to consume daily for a period of 12 weeks.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Depression score | The Centre for Epidemiologic Studies Depression Scale Revised Version (CESD-R) will be used to classify the patients according to their depression status. | 12 weeks | 
| Depression severity scale | The Patient Health Questionnaire-9 (PHQ-9) will be used to assess the severity scale for the patients. | 12 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Quality of life score | The life quality of patients will be measured using the Irritable bowel syndrome Quality of Life Questionnaire (IBS-QOL). | 12 weeks | 
| IBS severity score | Any changes in gastrointestinal symptoms severity related to IBS will be quantify using the Irritable bowel syndrome Severity Scoring System (IBS-SSS). | 12 weeks | 
| Acute stress biomarker | Morning blood sample will be collected to measure serum cortisol level among patients with IBS. | 12 weeks | 
| Depression biomarker | Blood samples collected will be analysed to measure the serum serotonin level of patients with IBS. | 12 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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probiotics, irritable bowel syndrome, subthreshold depression, IBS, subclinical depression