Effects of Akkermansia Muciniphila and Berberine Supplementation on Insulin Sensitivity in Night-shift Workers (Shift2Health)

Effects of Akkermansia Muciniphila and Berberine Supplementation on Insulin Sensitivity in Night-shift Workers: a Double-blind, Randomised, Placebo-controlled, Crossover Study Within the Shift2Health Project

Night shift work is associated with an increased risk of obesity, insulin resistance, and cardiometabolic disorders, largely due to circadian misalignment, disrupted sleep, and altered eating patterns. These behavioral and physiological disturbances impair glucose metabolism and are further influenced by the gut microbiota. In particular, the bacterium Akkermansia muciniphila has been linked to improved metabolic health, including enhanced insulin sensitivity, lipid regulation, and maintenance of intestinal barrier integrity. Berberine, a bioactive plant-derived compound, has demonstrated metabolic benefits, including upregulation of A. muciniphila, improvement of insulin sensitivity, and modulation of lipid metabolism.

Together, these complementary mechanisms suggest that combined A. muciniphila supplementation and berberine administration may synergistically improve metabolic health in shift workers by targeting gut microbiota composition and circadian-regulated metabolic pathways.

Based on this rationale, a double-blind, randomized, placebo-controlled, crossover study is being conducted in 200 night-shift workers from healthcare and industrial sectors in Austria and Denmark. Participants are stratified by age, sex, and work sector and randomly assigned to intervention sequences. Each participant receives either the combined supplement or placebo for 12 weeks, followed by a four-week washout, after which the alternate intervention is administered for another 12 weeks, with a total participation of 28 weeks.

Assessments are performed at four study visits and include anthropometry, body composition, blood pressure, and collection of blood, urine, and feces. Participants complete validated questionnaires on dietary intake, lifestyle, work schedules, and general health to monitor behavioral patterns throughout the study. Dietary intake is recorded for four days prior to each sampling visit in consideration of shift schedules. Sleep duration and quality are monitored via diaries and actigraphy and aligned with dietary records. Circadian variation is minimized by standardizing sampling times and implementing a fasting and synchronization period prior to visits.

The primary outcome is insulin sensitivity, measured by HOMA-IR. Secondary exploratory outcomes include gut microbiota composition and diversity, biomarkers of intestinal permeability and inflammation, lipid profiles, body composition, sleep quality, and dietary behavior.

These measures collectively provide a comprehensive evaluation of the metabolic, microbiome, and circadian effects of combined A. muciniphila and berberine supplementation in night-shift workers.

Study Overview

• Status: Recruiting
• Conditions: Circadian Rhythm Disorders; Obesity & Overweight; Prediabetes (Insulin Resistance, Impaired Glucose Tolerance); Gut Microbiota Modulation
• Intervention / Treatment: Dietary supplement: Verum (A); Dietary supplement: Placebo (B)

• Study Type: Interventional
• Enrollment (Estimated): 200
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Miriam Ressler, PhD; Phone Number: +4331654536677; Email: miriam.ressler@fh-joanneum.at

Study Locations

• Austria
  • Styria
    • Graz, Styria, Austria, 8020
      • Recruiting
      • FH JOANNEUM University of Applied Sciences
      • Contact: Miriam Ressler, PhD; Phone Number: +4331654536677; Email: miriam.ressler@fh-joanneum.at

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• Health care or industrial shift worker
• Employed or self-employed working ≥ 24 h/week
• Current night shift work (night shift defined as a work schedule that includes at least 3 hours of work between 00:00 and 5:00) with at least 2 consecutive nights/month
• Night shift work duration > 3 years
• 4 or more night shifts/month

Exclusion Criteria:

• BMI of 40 kg/m² or higher
• Pregnancy or planned pregnancy within 6 months of enrolment or breastfeeding women
• Bariatric surgery
• Surgery in the 3 months prior to the study or planned surgery in the next 6 months that, in the opinion of the investigators, could potentially affect the outcome of the study
• Diagnosed diabetes type 1 or type 2
• Uncontrolled thyroid disease (confirmed by clinically significant abnormal TSH/T4 levels without stable medication for more than 3 months)
• Chronic diseases (renal failure, active hepatitis, liver cirrhosis, myocardial infarction within the last 2 years, stroke, chronic obstructive pulmonary disease or cancer)
• Immunodeficiency syndrome, active autoimmune or autoinflammatory disease (e.g. multiple sclerosis, lupus, rheumatoid arthritis), inflammatory bowel disease (e.g. IBS or ulcerative colitis) and acute episodes of atopic diseases (atopic dermatitis, asthma, type 1 allergies such as hay fever). Grave's disease, Hashimoto thyroiditis, Celiac disease, sarcoidosis, Lichen planus, are allowed, if well treated and stable
• Regular intake of anticoagulants
• Known allergy to any inactive or active ingredients in the study products
• Participation in other clinical intervention trials during the study
• Current or planned participation in a weight loss program (including intermittent fasting), extreme diet, or vigorous exercise (e.g., running, fast cycling, swimming laps, or playing intense sports that quickly raise your heart rate)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: AB Group; Participants will first receive Verum (A) for 3 months. After a 4-week washout period, they will receive Placebo (B) for 3 months.	Dietary supplement: Verum (A); 1 capsule of A. muciniphila (pasteurized, initial quantity of 10^30 TFU, heat inactivated) and 1 capsule of 500 mg berberine hydrochloride per day.; Dietary supplement: Placebo (B); 1 capsule of A. muciniphila placebo and 1 capsule of berberine placebo (both identical to verum regarding the shape, size, colour, and matched in excipients) per day.
Experimental: BA Group; Participants will first receive Placbo (B) for 3 months. After a 4-week washout period, they will receive Verum (A) for 3 months.	Dietary supplement: Verum (A); 1 capsule of A. muciniphila (pasteurized, initial quantity of 10^30 TFU, heat inactivated) and 1 capsule of 500 mg berberine hydrochloride per day.; Dietary supplement: Placebo (B); 1 capsule of A. muciniphila placebo and 1 capsule of berberine placebo (both identical to verum regarding the shape, size, colour, and matched in excipients) per day.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change of 3-months supplementation with A. muciniphila and berberine on insulin resistance using HOMA-IR compared to placebo	Homeostasis Model Assessment of Insulin Resistance, calculated as (fasting insulin (μU/ml) x fasting glucose (mmol/l)) / 22.5, will be assessed to calculate the change between baseline and endpoint in the two periods	At the beginning and the end of each intervention period (week 0, 12, 16, 28)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in gut microbiom composition between the baseline and endpoint change in the two periods	Gene sequencing of the 16S rRNA is performed on the stool samples to compare microbiota diversity and relative abundance	At the beginning and the end of each intervention period (week 0, 12, 16, 28)
Change in FABPi between the baseline and endpoint change in the two periods	Measurement of FABP intestinal (FABPi) in blood (pg/mL)	At the beginning and the end of each intervention period (week 0, 12, 16, 28)
Change in zonulin between the baseline and endpoint change in the two periods	Measurement of zonulin in blood (ng/mL)	At the beginning and the end of each intervention period (week 0, 12, 16, 28)
Change in LPB between the baseline and endpoint change in the two periods	Measurement of lipopolysaccharide-binding protein (LPB) in blood (pg/mL)	At the beginning and the end of each intervention period (week 0, 12, 16, 28)
Change in CRP between the baseline and endpoint change in the two periods	Analysis of high-sensitive C-reactive protein (hs-CRP, mg/L) in blood	At the beginning and the end of each intervention period (week 0, 12, 16, 28)
Change in stool short-chain fatty acids (SCFA) between the baseline and endpoint change in the two periods	SCFA will be extracted and quantitatively analysed by GC-MS (µmol/g)	At the beginning and the end of each intervention period (week 0, 12, 16, 28)
Change in blood lipid profile and cardiovascular markers between the baseline and endpoint change in the two periods	Measurement of cholesterol (mmol/L), low-density lipoprotein cholesterol (LDL-C, mmol/L), high-density lipoprotein (HDL-C, mmol/L), and triglyceride levels (TG, mmol/L) in blood	At the beginning and the end of each intervention period (week 0, 12, 16, 28)
Change in blood pressure between the baseline and endpoint change in the two periods	Systolic BP (mmHG) and diastolic BP (mmHG)	At the beginning and the end of each intervention period (week 0, 12, 16, 28)
Change in melatonin between the baseline and endpoint change in the two periods	6-sulfatoxymelatonin in urine (µg/L)	At the beginning and the end of each intervention period (week 0, 12, 16, 28)
Change in BMI between the baseline and endpoint change in the two periods	Body mass index (BMI)	At the beginning and the end of each intervention period (week 0, 12, 16, 28)
Change in body composition between the baseline and endpoint change in the two periods	Bioelectrical Impedance Analysis (BIA)	At the beginning and the end of each intervention period (week 0, 12, 16, 28)
Change in metabolomics at the end of the two periods	Metabolomic profiles obtained with LC-MS/MS	At the beginning and the end of each intervention period (week 12, week 28)

Collaborators and Investigators

• Sponsor: FH Joanneum Gesellschaft mbH
• Collaborators: Medical University of Vienna; Erasmus Medical Center; University of Vienna; Københavns Universitet

Study record dates

Study Major Dates

• Study Start (Actual): January 20, 2026
• Primary Completion (Estimated): October 1, 2027
• Study Completion (Estimated): February 1, 2028

Study Registration Dates

• First Submitted: January 27, 2026
• First Submitted That Met QC Criteria: February 23, 2026
• First Posted (Actual): February 27, 2026

Study Record Updates

• Last Update Posted (Actual): February 27, 2026
• Last Update Submitted That Met QC Criteria: February 23, 2026
• Last Verified: January 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Endocrine System Diseases; Nervous System Diseases; Nutrition Disorders; Metabolic Diseases; Overnutrition; Body Weight; Glucose Metabolism Disorders; Diabetes Mellitus; Hyperinsulinism; Hyperglycemia; Pathological Conditions, Signs and Symptoms; Nutritional and Metabolic Diseases; Signs and Symptoms; Overweight; Obesity; Insulin Resistance; Prediabetic State; Glucose Intolerance; Chronobiology Disorders
• Other Study ID Numbers: 1306/2025; 101080788 (Other Grant/Funding Number: Horizon Europe)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No