To the best of our knowledge, this is the first study investigating the relationship between sleep factors and gallstone disease within a large, nationally representative sample. Our study revealed a significant association between both sleep duration and trouble sleeping with gallstone disease, with a significant dependency on BMI in this relationship. Specifically, we noted an inverse correlation between sleep duration and gallstone disease, particularly pronounced among individuals classified as overweight and obese. Conversely, trouble sleeping demonstrated a positive association with gallstone disease, particularly notable within the normal weight and obesity subgroups.
Currently, research on the impact of sleep factors on the incidence of gallstone disease remains limited. While previous studies have not established a clear relationship between sleep duration and gallstone disease, they have identified poor sleep quality associated with gallstone disease (27). Furthermore, an observational cohort study has shown a significant association between obstructive sleep apnea and gallstone disease (28). In contrast to prior research, our study found significant associations between both sleep duration and sleep difficulty with gallstone disease, and these associations varied across different BMI groups. Sleep plays a crucial role in maintaining metabolic homeostasis and energy balance (29), and a high BMI has been identified as a risk factor for gallstone disease (9). Therefore, investigating the influence of sleep factors within different BMI groups on gallstone disease holds potential clinical application value for the prevention of gallstone disease. However, further basic and clinical research is necessary in this area.
Sleep plays a pivotal role in regulating biological rhythms, which in turn govern many of our physiological activities (30). Therefore, disruption of biological rhythms caused by sleep factors is a potential mechanism for the onset of gallstones. Circadian rhythm-related transcription factors regulate the expression of genes encoding key enzymes in hepatic bile acid and cholesterol metabolism (31). Disruptions in circadian rhythm have been associated with abnormal hepatic bile acid and cholesterol metabolism, thereby promoting gallstone formation (32). Additionally, inflammation is a key factor in the pathogenesis of gallstone disease. While sleep can bolster immune defense, sleep disturbances can trigger inflammatory responses (33). A meta-analysis has revealed that shorter sleep duration is linked to higher levels of C-reactive protein (CRP), and sleep disturbances are associated with elevated levels of CRP and IL-6 (34). The increase of these inflammatory factors may promote the occurrence of gallstone disease (35, 36). Moreover, sleep disorders and insufficient sleep can precipitate dysbiosis of the gut microbiota, characterized by an elevated Firmicutes/Bacteroidetes Ratio (37), increased Desulfovibrionaceae (38), and decreased Lactobacillaceae and Bifidobacteriaceae (39), etc. These alterations in the microbiota have been associated with gallstone formation (40–42). Nonetheless, despite these insights, relevant research remains scarce, necessitating further investigation to elucidate specific mechanisms.
Our research utilized data from a large, nationally representative population sample, thereby enhancing the reliability and representativeness of our study. However, several limitations should be acknowledged. Firstly, owing to the cross-sectional study design, causal inference between sleep factors and the prevalence of gallstone disease cannot be established. It remains plausible that sleep factors may influence gallstone disease, or conversely, symptoms of gallstone disease may disrupt sleep patterns. To ascertain and validate our observations, well-designed prospective studies are warranted. Secondly, the NHANES data concerning sleep factors and gallstone disease are self-reported, and inevitably susceptible to recall bias. Future studies leveraging sleep monitoring techniques and electronic health records could offer valuable insights into this relationship.