The Efficacy of Pasteurised Akkermansia Muciniphila in Healthy Medical Workers (MENTAkHEALTH)

The Effects of the Anti-inflammatory Microbe - Pasteurized Akkermansia Muciniphila (PAM) on Symptoms of Somatic and Mental Stress in Healthcare Professionals

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.

Study Overview

• Status: Completed
• Conditions: Healthy; Stress; Dietary Supplement
• Intervention / Treatment: Dietary supplement: Pasteurized Akkermansia muciniphila; Dietary supplement: Placebo

Detailed Description

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
• Enrollment (Actual): 202
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Poland
  • Zachodniopomorskie
    • Szczecin, Zachodniopomorskie, Poland, 70-210
      • Pomeranian Medical University in Szczecin
    • Szczecin, Zachodniopomorskie, Poland, 71-240
      • Center fo Medical Simulation

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Pasteurized Akkermansia muciniphila; pasteurized A.muciniphila (Pasteurized, 3x10^10 bacteria per day) as supplement for 3 months,	Dietary supplement: Pasteurized Akkermansia muciniphila; 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; Other Names: PAM
Placebo Comparator: Placebo; placebo administered for 3 months once a day	Dietary supplement: Placebo; 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; Other Names: PBO

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Stress intensity	serum dehydroepiandrosterone sulfate (DHEAS) in blood	baseline
Stress intensity	serum dehydroepiandrosterone sulfate (DHEAS) in blood	1 month
Stress intensity	serum dehydroepiandrosterone sulfate (DHEAS) in blood	3 months
Cardiovascular marker of stressor intensity	blood pressure	baseline
Cardiovascular marker of stressor intensity	blood pressure	1 month
Cardiovascular marker of stressor intensity	blood pressure	3 months
Cardiovascular marker of stressor intensity	heart rate	baseline
Cardiovascular marker of stressor intensity	heart rate	1 month
Cardiovascular marker of stressor intensity	heart rate	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.	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.	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.	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	baseline
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	1 month
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	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	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	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	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.	baseline
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.	1 month
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.	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.	baseline
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.	1 month
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.	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; - Applied to me to some degree, or some of the time; - Applied to me to a considerable degree, or a good part of time; - 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	baseline
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; - Applied to me to some degree, or some of the time; - Applied to me to a considerable degree, or a good part of time; - 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	1 month
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; - Applied to me to some degree, or some of the time; - Applied to me to a considerable degree, or a good part of time; - 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	3 months
Occurrence of Irritable Bowel Syndrome	Rome IV criteria	baseline
Occurrence of Irritable Bowel Syndrome	Rome IV criteria	1 month
Occurrence of Irritable Bowel Syndrome	Rome IV criteria	3 months
Occurence and severity of gastrointestinal symptoms	Gastrointestinal Symptom Rating Scale (GSRS)	baseline
Occurence and severity of gastrointestinal symptoms	Gastrointestinal Symptom Rating Scale (GSRS)	1 month
Occurence and severity of gastrointestinal symptoms	Gastrointestinal Symptom Rating Scale (GSRS)	3 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Insulin resistance	HOMA-Homeostasis Model Assessment calculated from fasted glycemia and insulinemia	3 months
Concentration of blood lipids	Analysis of circulating lipids : total, LDL and HDL cholesterol (mg/dl), triglycerides (md/dl)	3 months
Obesity	Body weight	3 months
Microbiota composition	next generation sequencing	baseline
Microbiota composition	next generation sequencing	1 month
Microbiota composition	next generation sequencing	3 months
A. muciniphila count in stool	real-time quantitative PCR (qPCR)	baseline
A. muciniphila count in stool	real-time quantitative PCR (qPCR)	1 month
A. muciniphila count in stool	real-time quantitative PCR (qPCR)	3 months
Total bacteria count in stool	real-time quantitative PCR (qPCR)	baseline
Total bacteria count in stool	real-time quantitative PCR (qPCR)	1 month
Total bacteria count in stool	real-time quantitative PCR (qPCR)	3 months
Short chain fatty acids content in stool	quadrupole mass spectrometer and high performance liquid chromatograph	baseline
Short chain fatty acids content in stool	quadrupole mass spectrometer and high performance liquid chromatograph	1 month
Short chain fatty acids content in stool	quadrupole mass spectrometer and high performance liquid chromatograph	3 months
Immune phenotypes of peripheral blood mononuclear cells (PBMCs)	single-cell genomics (scRNA-seq and scATAC-seq) analyses (in blood)	baseline
Immune phenotypes of peripheral blood mononuclear cells (PBMCs)	single-cell genomics (scRNA-seq and scATAC-seq) analyses (in blood)	1 month
Immune phenotypes of peripheral blood mononuclear cells (PBMCs)	single-cell genomics (scRNA-seq and scATAC-seq) analyses (in blood)	3 months
Inflammatory mediators concentrations in blood	high-throughput protein biomarker analysis with the advent of Proximity Extension Assay	baseline
Inflammatory mediators concentrations in blood	high-throughput protein biomarker analysis with the advent of Proximity Extension Assay	1 month
Inflammatory mediators concentrations in blood	high-throughput protein biomarker analysis with the advent of Proximity Extension Assay	3 months
Zonulin concentration in stool	enzyme-linked immunosorbent assay (ELISA)	baseline
Zonulin concentration in stool	enzyme-linked immunosorbent assay (ELISA)	1 month
Zonulin concentration in stool	enzyme-linked immunosorbent assay (ELISA)	3 months
Calprotectin concentration in stool	enzyme-linked immunosorbent assay (ELISA)	baseline
Calprotectin concentration in stool	enzyme-linked immunosorbent assay (ELISA)	1 month
Calprotectin concentration in stool	enzyme-linked immunosorbent assay (ELISA)	3 months
Lipopolysaccharide concentration in blood	enzyme-linked immunosorbent assay (ELISA)	baseline
Lipopolysaccharide concentration in blood	enzyme-linked immunosorbent assay (ELISA)	1 month
Lipopolysaccharide concentration in blood	enzyme-linked immunosorbent assay (ELISA)	3 months
Adiposity	Fat mass/fat free mass evaluated by bioimpedance	baseline
Adiposity	Fat mass/fat free mass evaluated by bioimpedance	1 month
Adiposity	Fat mass/fat free mass evaluated by bioimpedance	3 months
Obesity	Body weight	baseline
Obesity	Body weight	1 month
Dietary habits	the frequency of certain food consumption (rank score) by means of validated Food Frequency Questionnaire (FFQ).	baseline
Physical activity	International Physical Activity Questionnaire. Results can be reported in categories (low activity levels, moderate activity levels or high activity levels) or as a continuous variable (MET minutes a week).	baseline
Functions of peripheral blood mononuclear cells (PBMCs)	mass cytometry (CyTOF)	baseline
Functions of peripheral blood mononuclear cells (PBMCs)	mass cytometry (CyTOF)	1 month
Functions of peripheral blood mononuclear cells (PBMCs)	mass cytometry (CyTOF)	3 months
Insulin resistance	HOMA-Homeostasis Model Assessment calculated from fasted glycemia and insulinemia	baseline
Insulin resistance	HOMA-Homeostasis Model Assessment calculated from fasted glycemia and insulinemia	1 month
carbohydrate metabolism	glycated hemoglobin (HbA1c)	baseline
carbohydrate metabolism	glycated hemoglobin (HbA1c)	1 month
carbohydrate metabolism	glycated hemoglobin (HbA1c)	3 months
Concentration of blood lipids	Analysis of circulating lipids : total, LDL and HDL cholesterol (mg/dl), triglycerides (md/dl)	baseline
Concentration of blood lipids	Analysis of circulating lipids : total, LDL and HDL cholesterol (mg/dl), triglycerides (md/dl)	1 month

Collaborators and Investigators

• Sponsor: Pomeranian Medical University Szczecin
• Collaborators: Charite University, Berlin, Germany; Imperial College London; SANPROBI SPOLKA Z OGRANICZONA ODPOWIEDZIALNOSCIA SPOLKA KOMANDYTOWA; THE AKKERMANSIA COMPANY; MAX DELBRUECK CENTRUM FUER MOLEKULARE MEDIZIN IN DER HELMHOLTZ-GEMEINSCHAFT (MDC) - MDC

Publications and helpful links

General Publications

• Depommier C, Everard A, Druart C, Plovier H, Van Hul M, Vieira-Silva S, Falony G, Raes J, Maiter D, Delzenne NM, de Barsy M, Loumaye A, Hermans MP, Thissen JP, de Vos WM, Cani PD. Supplementation with Akkermansia muciniphila in overweight and obese human volunteers: a proof-of-concept exploratory study. Nat Med. 2019 Jul;25(7):1096-1103. doi: 10.1038/s41591-019-0495-2. Epub 2019 Jul 1.
• Schneeberger M, Everard A, Gomez-Valades AG, Matamoros S, Ramirez S, Delzenne NM, Gomis R, Claret M, Cani PD. Akkermansia muciniphila inversely correlates with the onset of inflammation, altered adipose tissue metabolism and metabolic disorders during obesity in mice. Sci Rep. 2015 Nov 13;5:16643. doi: 10.1038/srep16643.
• Druart C, Plovier H, Van Hul M, Brient A, Phipps KR, de Vos WM, Cani PD. Toxicological safety evaluation of pasteurized Akkermansia muciniphila. J Appl Toxicol. 2021 Feb;41(2):276-290. doi: 10.1002/jat.4044. Epub 2020 Jul 28.
• Cani PD, Depommier C, Derrien M, Everard A, de Vos WM. Akkermansia muciniphila: paradigm for next-generation beneficial microorganisms. Nat Rev Gastroenterol Hepatol. 2022 Oct;19(10):625-637. doi: 10.1038/s41575-022-00631-9. Epub 2022 May 31. Erratum In: Nat Rev Gastroenterol Hepatol. 2022 Oct;19(10):682. doi: 10.1038/s41575-022-00650-6.

Helpful Links

• EC official website with research results

Study record dates

Study Major Dates

• Study Start (Actual): October 24, 2023
• Primary Completion (Actual): March 10, 2025
• Study Completion (Actual): March 10, 2025

Study Registration Dates

• First Submitted: January 30, 2023
• First Submitted That Met QC Criteria: February 12, 2023
• First Posted (Actual): February 22, 2023

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: March 13, 2025
• Last Verified: March 1, 2025

More Information

Terms related to this study

• Keywords: stress; metabolome; microbiota; postbiotic; immunometabolism
• Other Study ID Numbers: 101095540

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED
• IPD Plan Description: Personal data will be pseudonymised and encrypted, and after the purpose of processing has ceased to exist, they will be deleted or made anonymous.; Personal data will be processed in compliance with the technical and organizational measures referred to in Regulation (EU) 2016/679 of the European Parliament and of the Council of 27 April 2016 and the Data Protection Policy at PMU.; Research data will be made available in the open research data repository, at the latest when the research article is published, after the end of its analysis.; There are no restrictions or obstacles preventing full disclosure of data.; Sharing data requires no consent of the study participants as for the anonymous character of the study; Only data from sequencing analyzes will be stored indefinitely in the repository https://qiita.ucsd.edu/; The remaining data will be deposited for a minimum of 10 years in the ZENODO repository

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No