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.
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
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
Crossover
Verum (A)
Dietary supplement1 capsule of A. muciniphila (pasteurized, initial quantity of 10\^30 TFU, heat inactivated) and 1 capsule of 500 mg berberine hydrochloride per day.
Placebo (B)
Dietary supplement1 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.
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
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
Change in FABPi between the baseline and endpoint change in the two periods
Measurement of FABP intestinal (FABPi) in blood (pg/mL)
Change in zonulin between the baseline and endpoint change in the two periods
Measurement of zonulin in blood (ng/mL)
Change in LPB between the baseline and endpoint change in the two periods
Measurement of lipopolysaccharide-binding protein (LPB) in blood (pg/mL)
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FH Joanneum Gesellschaft mbH
Lead sponsor
Medical University of Vienna
Collaborator
Københavns Universitet
Collaborator
Erasmus Medical Center
Collaborator
University of Vienna
Collaborator
