Introduction: Metabolic syndrome (MetS) is a chronic metabolic disorder whose global prevalence continues to rise, imposing a significant burden on public health. With the development of round-the-clock societies, shift work has become increasingly commonplace. A growing body of epidemiological evidence indicates that circadian rhythm disruption constitutes a predictable risk factor for MetS; however, the precise mechanisms underlying this relationship remain inadequately understood. This study employed golden hamsters as a model to investigate the effects of circadian rhythm disruption simulated by cyclic light (CL) exposure on MetS. Methods: Thirty-three male golden hamsters (7 weeks old, body weight 120–160 g) were randomly assigned to four groups for a 6-week intervention: the Control group (normal light + normal diet, ND), the high-fat diet group (normal light + HFD, to induce a MetS model), the cyclic light group (CL + normal diet, CL), and the CL + HFD group (CL + HFD). Outcome measures included metabolic indicators, hepatic histopathology, and gut microbiota (analyzed via 16S rDNA sequencing). Results: The stability of the MetS model was assessed through measurements of body weight, fasting blood glucose, and total cholesterol levels. The results indicated that CL exposure may further aggravate metabolic disorders associated with MetS. Furthermore, it was observed that CL exposure intensified MetS-related disturbances in gut microbiota, evidenced by an increase in α-diversity and distinct separation in β-diversity. CL exposure in the MetS model golden hamsters resulted in a reduced abundance of Bacteroidetes and Weissella, alongside an overgrowth of Helicobacter. discussion: 4. DISCUSSION The present study systematically investigated the combined effects of cyclic light exposure induced circadian rhythm disruption and high-fat diet on metabolic homeostasis, hepatic pathology, and gut microbiota composition in LVG golden hamsters. A key finding was that both CL and HFD alone disrupted metabolic indicators—including increased body weight, FBG, TC, and TG—while their combination exacerbated these dysregulations39. This is consistent with epidemiological evidence linking shift work to elevated MetS risk, particularly in populations with unhealthy dietary patterns. Notably, the CL+HFD group exhibited more severe hepatic steatosis, with vacuolar lipid accumulation, hepatocellular swelling, and inflammatory infiltration, which aligns with preclinical studies demonstrating that circadian misalignment amplifies HFD-induced hepatic lipotoxicity by disrupting clock-controlled genes (e.g., Per2, Rev-erbα) involved in lipid metabolism40. These results collectively confirm a synergistic effect of circadian disruption and HFD on metabolic and hepatic dysfunction, highlighting the clinical relevance for shift workers at high risk of MetS. A critical novelty of this study lies in its characterization of gut microbiota as a potential mediator of the above pathological processes. Alpha diversity analysis revealed that CL+HFD significantly increased microbial richness (Chao1), diversity (Shannon), and evenness (Pielou’s index), whereas HFD alone had no such effect—suggesting that circadian disruption may be a dominant driver of gut microbial community expansion. Beta diversity analyses (PCA, CoA, NMDS) further verified that CL+HFD induced the most profound structural divergence from the control group, indicating a synergistic perturbation of microbial ecology. At the genus level, HFD alone downregulated Weissella (a probiotic genus associated with short-chain fatty acid (SCFA) production) and upregulated pathogenic Escherichia-Shigella and Helicobacter, which is consistent with reports that HFD promotes gut dysbiosis by favoring pro-inflammatory taxa. CL alone also elevated Helicobacter abundance. And the abundance of Helicobacter was abnormally elevated, while the abundance of the beneficial bacterium Weissella was also markedly decreased in the HFD+CL group. These findings demonstrate that the combined effect of HFD and cyclic light further exacerbates the depletion of beneficial gut bacteria and the aberrant proliferation of Helicobacter. The marked depletion of Weissella observed in the present study has emerged as a key clue for deciphering the mechanisms underlying metabolic dysregulation9. As a pivotal producer of short-chain fatty acids (SCFAs) in the gut microbiota, Weissella generates butyrate via fermenting host-ingested dietary fiber; this metabolite not only serves as the primary energy source for colonic epithelial cells but also orchestrates lipolysis and energy expenditure by activating G protein-coupled receptors (GPR41/43)41. The profound depletion of Weissella in the CL+HFD group directly precipitates a reduction in intestinal butyrate levels, which in turn disrupts the homeostasis of the "butyrate-GPR41/43-AMPK" signaling cascade. Specifically, decreased AMPK phosphorylation not only suppresses fatty acid oxidation but also upregulates the expression of hepatic triglyceride synthases (e.g., DGAT1), ultimately exacerbating hyperlipidemia and hepatic steatosis. In striking contrast, the synergistic overgrowth of Helicobacter amplifies metabolic impairment through multiple avenues: its secreted lipopolysaccharide (LPS) directly compromises tight junction proteins (e.g., Occludin and ZO-1) between intestinal epithelial cells, increasing intestinal permeability and enabling LPS translocation into the systemic circulation, thereby triggering "metabolic endotoxemia"42. Circulating LPS subsequently engages Toll-like receptor 4 (TLR4) to activate the NF-κB inflammatory pathway, eliciting the release of proinflammatory cytokines such as TNF-α and IL-6—central mediators in inducing insulin resistance. Specifically, these cytokines impair glucose metabolism by inhibiting the tyrosine phosphorylation of insulin receptor substrate 1 (IRS-1), which blocks insulin signal transduction to adipose and muscle tissues. The core findings of this study provide novel targeted insights into the prevention and intervention of MetS in high-risk populations, such as shift workers. Its clinical translational value lies in the integration of "precision gut microbiota modulation" and "lifestyle intervention". Circadian rhythm disruption in shift workers is often unavoidable; therefore, based on the microbial signatures uncovered in this study, tailored intervention strategies can be designed43. On one hand, multi-strain probiotic formulations centered on Weissella could be developed, as exogenous supplementation of this bacterium may restore the abundance of beneficial gut microbes and re-establish the metabolic regulatory functions of SCFAs44. On the other hand, in light of the characteristic that cyclic light combined with a high-fat diet synergistically exacerbates gut dysbiosis, gut-microbiota-friendly dietary regimens can be formulated for shift workers—for instance, increasing intake of soluble dietary fibers such as whole grains and inulin4445. Such components not only serve as nutritional substrates for beneficial bacteria like Weissella but also inhibit the proliferation of pathogenic bacteria (e.g., Helicobacter) by lowering intestinal pH46. Notably, CL intervention alone in this study led to increased Helicobacter abundance, suggesting that even shift workers on a normal diet face an underlying risk of gut dysbiosis. This finding provides a basis for stratified metabolic risk management: for individuals with long-term shift work exposure, the abundance ratio of intestinal Helicobacter to Weissella could be used as an early warning biomarker, which, when combined with blood glucose and lipid monitoring, enables early detection and intervention of MetS. Discussion: Circadian rhythm disruption is an independent risk factor for MetS. It further exacerbates metabolic indicators by inducing gut microbiota dysbiosis and promoting the growth of harmful bacteria. Future research should integrate functional metabolomics with faecal microbiota transplantation studies to validate causal mechanisms and explore clinical translational value. conclusion: Conclusions: CL and HFD synergistically promote MetS via gut microbiota dysbiosis, providing insights for microbiota-targeted interventions in high-risk populations like shift workers. Conclusions: Circadian rhythm disruption is an independent risk factor for MetS. It exacerbates the pathological progression of MetS by reducing beneficial bacteria and promoting the growth of harmful bacteria, thereby further damaging its metabolic indicators.
Wáng et al. (Tue,) studied this question.