Clinical trial NCT03370458: Lactobacillus Plantarum DR7 for Gut-Brain-Axis Benefits
Official title: Lactobacillus Plantarum DR7 for Gut-Brain-Axis Benefits
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Stress
Lead sponsor: Universiti Sains Malaysia
Sponsor class: OTHER
Collaborators: name: Clinical Nutrition Sdn Bhd
First posted: 2017-12-12
Enrollment: 118
Sex: ALL
Minimum age (years): 18
Maximum age (years): 60
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Placebo and DR7 will be administered via a parallel design
Primary purpose: TREATMENT

Brief summary: This project aims to study the benefits of probiotics namely Lactobacillus plantarum DR7 for brain health properties, primarily alleviation of stress, among adults in Malaysia aged from 18 to 60 years.

Detailed description: Probiotics are "live microorganisms which, when administered in adequate amounts, can confer health benefits on the host". Probiotics, which beneficially affect the host by improving the intestinal microbial balance, may affect the immune response, thus boosting the body system to combat against diseases. While numerous microorganisms that may confer health benefits to the host, the most widely studied probiotics are from the Lactobacillus genera. For the past few decades, probiotics have been studied extensively for their beneficial effects mainly on the host's guts. Recently, probiotics are studied for their promising potentials along the gut-brain-axis. The 'gut-brain-axis' is a bidirectional communication system, dynamic for maintaining homeostasis. Many studies show that certain strains of Lactobacillus improved human's health such as reducing the occurrence of diarrhea caused by rotavirus infections, antibiotic treatment, chemotherapy, or lactose intolerance, reduced irritable bowel syndrome symptoms and treating atopic diseases. Lactobacillus have also gained increasing evidences as an effective therapy in preventing respiratory tract infections such as sinusitis, bronchitis and pneumonia. While the precise mechanisms of using Lactobacillus in management of respiratory infections are largely unknown, speculations include: Lactobacillus compete against pathogens; increase the barrier function in respiratory epithelium; immunostimulatory effects by enhancing cellular immunity with increased activity of natural killer cells and macrophages in airways. Lactobacilli, as one of the largest genera for probiotic microorganisms have been researched to alleviate stress, anxiety and/or depression disorders.

Lactobacillus plantarum DR7 was isolated from fresh cow's milk in Penang, Malaysia. In-vitro evaluation has shown that this putative probiotic strain adhere to the criteria of probiotic characteristics; a) resistant towards acid and bile conditions of the upper gastrointestinal tract, b) does not possess antibiotic resistance as per requirement of the European Food Safety Authority (EFSA), c) able to adhere to mucin, d) has antioxidant properties, e) able to utilize prebiotics such as fructooligosaccharide (FOS), inulin and galactooligosaccharide (GOS), e) has a carbon metabolism profile adhering to the general patterns of lactobacilli, and f) possess antimicrobial properties against gastrointestinal pathogens. In-vivo evaluation using rats shown that this putative probiotic strain has gut protection properties; a) modulation of gastrointestinal microbial profile via suppressing gut pathogen populations and increasing the population of lactobacilli, b) decreasing pro-inflammatory cytokines and increasing anti-inflammatory cytokines in the plasma, and c) reducing inflammation in the lower intestines.

All these indicated that Lactobacillus plantarum DR7 has the potential to be an effective probiotic strain that modulate gut health and immunity. In addition, due to the alleviation of gastrointestinal stress, this strain may be beneficial along the gut-brain-axis to promote brain health as well.

Lactobacillus plantarum DR7 and placebo are produced under GMP and HALAL certified manufacturing facility. Probiotic Lactobacillus plantarum DR7 appears as light yellow powder. Sachets are stored away from direct sunlight and in below 30C according to the storage condition recommendations of the manufacturer. Each dose was supplied in an aluminium sachet and all sachets are identical in taste and appearance. Probiotic Lactobacillus plantarum DR7 does not contain any porcine or bovine ingredients.

The product contains Lactobacillus plantarum DR7 and maltodextrin as excipient while placebo contains only maltodextrin.

A total number of 124 healthy adults from age 18 -60 years old will be recruited for this study.

Eligibility criteria: Inclusion Criteria:

* Male or female subjects
* 18-60 years old
* Willing to commit throughout the experiment
* Have moderate stress and beyond, as per determined by PSS test

Exclusion Criteria:

* Type-1 diabetes (one of the main metabolite of Lactobacillus is acetic acid. Acetic acid has been reported to affect lipid metabolism in the liver and fat digestion in the pancreas in animal studies, and has been applied in obesity studies)
* Long term medication due to certain severe illness (certain medications may interfere with the survivability of Lactobacillus in the gut, for example the interactions between probiotics and warfarin
* HIV/AIDS (there has been no substantial data on the detrimental effects of probiotics on AIDS patients. However, AIDS patient may be immune-compromised in the sense of "leaky gut" that may lead to bacterial translocation, including translocation of Lactobacillus outside the gut environment, into the blood stream)
* Glucose-6-phosphate dehydrogenase (G6PD) deficiency (there has been no substantial data on the detrimental effects of probiotics on G6PD deficiency people. However, certain strains of probiotics have been reported to benefit RBC irregularity disorders such as spur cells formation. One of the main mechanisms, involve the alteration of RBC membrane. Although this is a benefit, we are unsure of the effects on G6PD deficiency people, with weaker RBC).

Primary outcomes:
measure: Alleviation of stress
timeFrame: 12 weeks
measure: Alleviation of depression
timeFrame: 12 weeks
measure: Enhancement of cognition ability
timeFrame: 12 weeks
Secondary outcomes:
measure: Alleviation of respiratory tract infections
timeFrame: 12 weeks
measure: Alleviation of gastrointestinal disorders
timeFrame: 12 weeks
measure: Enhancement of immunity
timeFrame: 12 weeks
Other outcomes:
Locations:
city: Pulau Pinang
country: Malaysia
facility: School of Industrial Technology, Universiti Sains Malaysia
state: Penang
Study officials:
affiliation: Universiti Sains Malaysia
name: MT Liong, PhD
role: PRINCIPAL_INVESTIGATOR
References: