The Efficacy of Pasteurised Akkermansia Muciniphila in Healthy Medical Workers

Pomeranian Medical University Szczecin202 enrolled

Overview

Gut microbiota alterations secondary to chronic stress might serve as a triggering factor towards manifestation of somatic and mental symptoms. The administration of pasteurised A. muciniphila MucT has the capability of supporting microbiota and improving the gut barrier integrity, which might lead to decrease of inflammation and the negative health consequences of stress in healthy participants.

The Gut-brain-microbiota axis (GBMA) is a bi-directional pathway, both neuronal and biochemical, between the intestine and the Central Nervous System (CNS). The gut microbiota plays a central role in gut-brain communication. The composition of intestinal microbiota and its functions play an important role in the pathogenesis of disorders of gut-brain interaction - both within the digestive tract and in the brain. Modulation of gut microbiota with the aid of probiotics, antibiotics, or germ-free feeding protocols significantly altered stressful event-induced behavioral outcomes in rodents. Moreover, the intake of various probiotics significantly improved stress-induced anxiety and depressive-like behaviors in mice. In humans, probiotics were also documented to display some beneficial effects on mental health, including alteration of emotional bias in healthy individuals, and alleviating stress and anxiety among stressed adults. Psychobiotics are imposed with certain limitations related to their standardization and end-shelf-life product stability. Therefore, the use of postbiotics, which contain bacterial metabolites or other bacteria derived fragments are viewed as novel solutions and alternatives to use of standard probiotics. One of novel postbiotics of interest among scientists and clinicians is pasteurized Akkermansia muciniphila MucT (PAM). Animal studies indicate that administration of Akkermansia muciniphila can ameliorate metabolic syndrome, obesity, diabetes, and inflammatory bowel disease in animals and has psychobiotic potential. Similar to live A. muciniphila, PAM could ameliorate several diseases as well. The mechanism of action of PAM - improving gut barrier integrity - suggests the potential use to reduce the negative effects of stress. Human studies shown that PAM is safety, what was confirmed in the Scientific Opinion of EFSA. Recently A. muciniphila was approved as the Novel Food. A proof of concept study will be conducted to verify the hypothesis that PAM reduces the psychological and somatic effects of stress.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

TRIPLE

Enrollment

202

Conditions

Stress Healthy Dietary Supplement

Interventions

Pasteurized Akkermansia muciniphilaDIETARY_SUPPLEMENT

PAM supplementation; packaging will be given to the subjects every one month during follow-up visits, with the instructions to take one dose every morning on an empty stomach

PlaceboDIETARY_SUPPLEMENT

PBO administration; packaging will be given to the subjects every one month during follow-up visits, with the instructions to take one dose every morning on an empty stomach

Eligibility

Sex: ALLMin age: 18 YearsMax age: 70 YearsHealthy volunteers:

Medical Language ↔ Plain English

Inclusion Criteria: * Working in a high stress hospital department, like: emergency, trauma, intensive care, surgery, internal diseases; * Written informed consent to participate in this study before any study-mandated procedure; * Body mass index (BMI) ≥18.5 kg/m2 and ≤ 35 kg/m2; * A willingness and motivation to follow the study protocol. Exclusion Criteria: * Diagnosis of autoimmune, neurological, immunocompromised, thyroid, inflammatory bowel diseases, irritable bowel syndrome, diabetes, cancer, and/or IgE-dependent allergy; * Psychiatric comorbidities, including mental retardation, organic brain dysfunction, or addiction (except nicotine and caffeine), intake of antipsychotic and antidepressive drugs; * Proton pump inhibitors usage; * The use of antibiotics and/or probiotics 4 weeks prior to the study; * Glucocorticosteroids and/or metformin treatment; * Dietary supplementation (except for vitamin D) within the three months before screening; * Specific restrictive (e.g. elimination, vegan, FODMAP, reduction) diet within the three months before screening; * Significant changes in physical activity 4 weeks before the trial entry; * Pregnancy or lactation; * Significant GI surgery within the last 6 months prior to or planned during the study; * Any other medication for management of IBS complaints like peppermint oil, bile acid binders; * Lactose intolerance; * Participation in another study during the last 30 days prior to and during the study; * Any other reason for exclusion as per investigator's judgment, e.g. insufficient compliance with study procedures.

Locations (2)

Pomeranian Medical University in Szczecin

Szczecin, West Pomeranian Voivodeship, Poland

Center fo Medical Simulation

Szczecin, West Pomeranian Voivodeship, Poland

Outcomes

Primary Outcomes

Stress intensity

serum dehydroepiandrosterone sulfate (DHEAS) in blood

Time frame: baseline

Stress intensity

serum dehydroepiandrosterone sulfate (DHEAS) in blood

Time frame: 1 month

Stress intensity

serum dehydroepiandrosterone sulfate (DHEAS) in blood

Time frame: 3 months

Cardiovascular marker of stressor intensity

blood pressure

Time frame: baseline

Cardiovascular marker of stressor intensity

blood pressure

Time frame: 1 month

Cardiovascular marker of stressor intensity

blood pressure

Time frame: 3 months

Cardiovascular marker of stressor intensity

heart rate

Time frame: baseline

Cardiovascular marker of stressor intensity

heart rate

Time frame: 1 month

Cardiovascular marker of stressor intensity

heart rate

Time frame: 3 months

Stress intensity

Perceived Stress Scale (PSS-10). Individual scores on the PSS can range from 0 to 40 with higher scores indicating higher perceived stress.

Data from ClinicalTrials.gov

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Time frame: baseline

Stress intensity

Perceived Stress Scale (PSS-10). Individual scores on the PSS can range from 0 to 40 with higher scores indicating higher perceived stress.

Time frame: 1 month

Stress intensity

Perceived Stress Scale (PSS-10). Individual scores on the PSS can range from 0 to 40 with higher scores indicating higher perceived stress.

Time frame: 3 months

Psychosocial working conditions

Copenhagen Psychosocial Questionnaire (COPSOQ). The scales of the COPSOQ are formed by adding the points of the individual questions of the scales by giving equal weights to each question. In most cases the questions have five response options. In these cases the weights are: 0, 25, 50, 75, and 100. The scale value is calculated as the simple average

Time frame: baseline

Psychosocial working conditions

Time frame: 1 month

Psychosocial working conditions

Time frame: 3 months

The recognition of the most common mental disorders

Primary Care Evaluation of Mental Disorders (PRIME-MD). The yes/no questionnaire serves as an initial screen for 5 general groups of mental disorders commonly found in the general population

Time frame: baseline

The recognition of the most common mental disorders

Primary Care Evaluation of Mental Disorders (PRIME-MD). The yes/no questionnaire serves as an initial screen for 5 general groups of mental disorders commonly found in the general population

Time frame: 1 month

The recognition of the most common mental disorders

Primary Care Evaluation of Mental Disorders (PRIME-MD). The yes/no questionnaire serves as an initial screen for 5 general groups of mental disorders commonly found in the general population

Time frame: 3 months

Depression

Patient Health Questionnaire-9 (PHQ-9). Nine items, each of which is scored 0 to 3, providing a 0 to 27 severity score.This score can then be referred to the accompanying PHQ-9 Scoring Box to interpret the TOTAL score.

Time frame: baseline

Depression

Time frame: 1 month

Depression

Time frame: 3 months

Depressive state

The Beck Depression Inventory (BDI). When the test is scored, a value of 0 to 3 is assigned for each answer and then the total score is compared to a key to determine the depression's severity. The standard cut-off scores were as follows: 0-18: indicates minimal depression 18-30: indicates mild depression 19-29: indicates moderate depression 30-63: indicates severe depression.

Time frame: baseline

Depressive state

Time frame: 1 month

Depressive state

Time frame: 3 months

Anxiety and stress

Depression Anxiety Stress Scale 21 (DASS-21). This is a set of three self-report scales designed to measure the emotional states of depression, anxiety and stress. The rating scale is as follows: 0 - Did not apply to me at all 1. \- Applied to me to some degree, or some of the time 2. \- Applied to me to a considerable degree, or a good part of time 3. \- Applied to me very much, or most of the time. SUBSCALES: DASS\_Anxiety = questions 2 + 4 + 7 + 9 + 15 + 19 + 20 DASS\_Depression = questions 3 + 5 + 10 + 13 + 16 + 17 + 21 DASS\_Stress = questions 1 + 6 + 8 + 11 + 12 + 14 +18

Time frame: baseline

Anxiety and stress

Time frame: 1 month

Anxiety and stress

Time frame: 3 months

Occurrence of Irritable Bowel Syndrome

Rome IV criteria

Time frame: baseline

Occurrence of Irritable Bowel Syndrome

Rome IV criteria

Time frame: 1 month

Occurrence of Irritable Bowel Syndrome

Rome IV criteria

Time frame: 3 months

Occurence and severity of gastrointestinal symptoms

Gastrointestinal Symptom Rating Scale (GSRS)

Time frame: baseline

Occurence and severity of gastrointestinal symptoms

Gastrointestinal Symptom Rating Scale (GSRS)

Time frame: 1 month

Occurence and severity of gastrointestinal symptoms

Gastrointestinal Symptom Rating Scale (GSRS)

Time frame: 3 months

Secondary Outcomes

Microbiota composition

next generation sequencing

Time frame: baseline

Microbiota composition

next generation sequencing

Time frame: 1 month

Microbiota composition

next generation sequencing

Time frame: 3 months

A. muciniphila count in stool

real-time quantitative PCR (qPCR)

Time frame: baseline

A. muciniphila count in stool

real-time quantitative PCR (qPCR)

Time frame: 1 month

A. muciniphila count in stool

real-time quantitative PCR (qPCR)

Time frame: 3 months

Total bacteria count in stool

real-time quantitative PCR (qPCR)

Time frame: baseline

Total bacteria count in stool

real-time quantitative PCR (qPCR)

Time frame: 1 month

Total bacteria count in stool

real-time quantitative PCR (qPCR)

Time frame: 3 months

Short chain fatty acids content in stool

quadrupole mass spectrometer and high performance liquid chromatograph

Time frame: baseline

Short chain fatty acids content in stool

quadrupole mass spectrometer and high performance liquid chromatograph

Time frame: 1 month

Short chain fatty acids content in stool

quadrupole mass spectrometer and high performance liquid chromatograph

Time frame: 3 months

Immune phenotypes of peripheral blood mononuclear cells (PBMCs)

single-cell genomics (scRNA-seq and scATAC-seq) analyses (in blood)

Time frame: baseline

Immune phenotypes of peripheral blood mononuclear cells (PBMCs)

single-cell genomics (scRNA-seq and scATAC-seq) analyses (in blood)

Time frame: 1 month

Immune phenotypes of peripheral blood mononuclear cells (PBMCs)

single-cell genomics (scRNA-seq and scATAC-seq) analyses (in blood)

Time frame: 3 months

Inflammatory mediators concentrations in blood

high-throughput protein biomarker analysis with the advent of Proximity Extension Assay

Time frame: baseline

Inflammatory mediators concentrations in blood

high-throughput protein biomarker analysis with the advent of Proximity Extension Assay

Time frame: 1 month

Inflammatory mediators concentrations in blood

high-throughput protein biomarker analysis with the advent of Proximity Extension Assay

Time frame: 3 months

Zonulin concentration in stool