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Loss of daily phase relations identified by multiomic analyses in acute pancreatitis
Heather Waddell1,2, Xiaozhong Zheng1, Lucile Neyton1
1Medical Research Council Centre for Inflammation Research, Queen's Medical Research Institute, The University of Edinburgh, Edinburgh, EH16 4TJ, UK.
Abstract:
Acute pancreatitis (AP) is sudden inflammation of the pancreas which can cause organ failure and death, and with no targeted therapies in the clinic, there is an imperative to identify new potential avenues for therapeutics discovery. This exploratory study investigates the potential role of circadian rhythms in AP pathogenesis. We integrated and analysed multiomics data, including transcriptomics, metabolomics, and clinical laboratory measurements, synthesised from peripheral whole blood samples obtained from AP patients. Our exploratory findings identified a potential association between circadian rhythm dysregulation and disease severity. Specifically, we observed that the rhythmic expression of circadian genes across a 24-h period, such as the circadian locomotor output cycles kaput (CLOCK) and the brain and muscle ARNT-Like 1 (BMAL1) gene, and a specific subset of metabolites may be altered in AP. These exploratory results provide a foundation for future investigations into the potential therapeutic implications of targeting circadian rhythms in AP. Additional studies are required to validate these findings and to elucidate the specific mechanisms involved.
Insights
Circadian rhythm disruption may worsen acute pancreatitis (AP) severity. This study found altered expression of circadian genes like CLOCK and BMAL1 and specific metabolites in AP patients, suggesting new therapeutic targets.
Area of Science:
- * Chronobiology and Gastroenterology
- * Multiomics in Disease Pathogenesis
Background:
- * Acute pancreatitis (AP) is a severe inflammatory condition lacking targeted therapies.
- * Understanding AP pathogenesis is crucial for developing novel treatments.
- * The role of circadian rhythms in AP remains largely unexplored.
Purpose of the Study:
- * To investigate the potential involvement of circadian rhythm dysregulation in AP.
- * To explore associations between circadian patterns and AP disease severity.
- * To identify potential multiomic biomarkers for AP.
Main Methods:
- * Integration and analysis of multiomics data (transcriptomics, metabolomics).
- * Utilized peripheral whole blood samples from AP patients.
- * Examined rhythmic gene expression and metabolite profiles over 24 hours.
Main Results:
- * Identified a potential link between circadian rhythm dysregulation and AP severity.
- * Observed altered rhythmic expression of key circadian genes (e.g., CLOCK, BMAL1).
- * Found alterations in a specific subset of metabolites in AP patients.
Conclusions:
- * Circadian rhythm dysregulation may play a role in AP pathogenesis.
- * CLOCK, BMAL1 genes, and specific metabolites show altered rhythmic expression in AP.
- * Findings support further research into targeting circadian rhythms for AP therapeutics.
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Pancreatitis is the inflammation of the pancreas, which occurs when the immune system becomes active and causes swelling, pain, and disruptions in organ function. Pancreatitis can manifest as either an acute or chronic condition.
Acute pancreatitis arises suddenly and lasts for a brief duration, while chronic pancreatitis is a long-term affliction...
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