Genetic and environmental circadian disruption induce weight gain through changes in the gut microbiome.
Level 5 - mechanism / opinion, no new human data
Preclinical animal model study (CEBM Level 5: bench/animal research)
PubMed 36334897 · doi:10.1016/j.molmet.2022.101628
What was done
The authors examined two mouse models of circadian disruption: a genetic model with suprachiasmatic nucleus Bmal1 deficiency (Bmal1 SCNfl/-) and an environmental model using wild-type mice exposed to simulated shift work (SSW). Core and accessory clock gene expression in gastrointestinal tissues was measured by qPCR. Energy balance and body composition were assessed via nuclear magnetic resonance, bomb calorimetry, food intake, and running-wheel activity; intestinal permeability was tested in Ussing chambers. Gut microbiota composition and function were analyzed with 16S rRNA sequencing, PICRUSt2.0, and targeted metabolomics. Causal impact was evaluated by transferring SSW-associated microbiota into germ-free recipient mice.
What was found
Both genetic and environmental circadian disruption models demonstrated desynchronization of peripheral gastrointestinal clocks and decreased microbial rhythmicity, particularly among taxa involved in short-chain fatty acid fermentation and lipid metabolism. Bmal1 SCNfl/- mice and SSW mice both developed increased body weight. Transfer of SSW-conditioned microbiota into germ-free mice directly induced weight gain and altered host peripheral and clock-controlled metabolic gene expression. The abstract reports directional changes but provides no specific numerical values, percentages, or statistical effect sizes.
Why it matters
This study demonstrates a functional, bidirectional mechanism linking intestinal clock desynchronization and gut dysbiosis to metabolic dysfunction during circadian disruption. It provides preclinical proof-of-concept that shift-work-related weight gain can be driven directly by disrupted microbiome rhythmicity.
Limits
The study was conducted entirely in rodent models, so applicability to human circadian misalignment and shift work remains unproven. The abstract does not report group sample sizes (n), baseline versus post-intervention numerical values, effect sizes, or confidence intervals.
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- supports Maintaining healthy sleep patterns and avoiding erratic sleep-wake behavior affects the microbiome and host regulation of weight and glucose metabolism.