Published online Dec 15, 2023. doi: 10.4251/wjgo.v15.i12.2169
Peer-review started: July 29, 2023
First decision: September 23, 2023
Revised: October 1, 2023
Accepted: October 30, 2023
Article in press: October 30, 2023
Published online: December 15, 2023
Processing time: 138 Days and 0.7 Hours
Gastroesophageal reflux disease (GERD) affects approximately 13% of the global population. However, the pathogenesis of GERD has not been fully elucidated. The development of metabolomics as a branch of systems biology in recent years has opened up new avenues for the investigation of disease processes. As a powerful statistical tool, Mendelian randomization (MR) is widely used to explore the causal relationship between exposure and outcome.
At present, there is still a significant lack of blood metabolomics research on GERD.
We used MR analysis to thoroughly investigate the causal relationships between 486 blood metabolites and GERD using data from a genome-wide association study (GWAS). Additionally, we identified the metabolic pathways that cause GERD. In addition to advancing our understanding of the pathophysiological mechanisms underlying GERD, the integration of metabolomics and genomics offers fresh perspectives on the early detection and management of the disease.
Two-sample MR analysis was used to assess the causal relationship between blood metabolites and GERD. A GWAS of 486 metabolites was the exposure, and two different GWAS datasets of GERD were used as endpoints for the base analysis and replication and meta-analysis. Using the MR Steiger filtration method to detect whether there is a reverse causal relationship between metabolites and GERD. In addition, metabolic pathway analysis was conducted using the online database based MetaboAnalyst 5.0 software.
The results of this study indicated significant associations between eight metabolites, levulinate (4-oxovalerate) [odd ratio (OR) 0.80, 95% confidence interval (CI): 0.72-0.89, P < 0.0001], stearate (18:0) (OR 0.77, 95%CI: 0.64-0.92, P = 0.004), adrenate (22:4n6) (OR 0.83, 95%CI: 0.74-0.94, P = 0.004), p-acetamidophenylglucuronide (OR 0.99, 95%CI: 0.99-1.00, P = 0.0002), kynurenine (OR 1.20, 95%CI: 1.07-1.35, P = 0.002), 1-linoleoylglycerophosphoethanolamine (OR 1.17, 95%CI: 1.05-1.31, P = 0.004), butyrylcarnitine (OR 1.09, 95%CI: 1.05-1.13, P < 0.0001), and guanosine (OR 1.10, 95%CI: 1.03-1.18, P = 0.003), and GERD. Bonferroni correction showed that butyrylcarnitine (OR 1.10, 95%CI: 1.05-1.16, P = 7.71 × 10-5) was the most reliable causal metabolite. Glycerophospholipid metabolism may be involved in the pathogenesis of GERD.
Through the integration of genomics and metabolomics, we found that butyrylcarnitine may be a potential biomarker for GERD.
The relationship between GERD and butyrilcarnitine needs further confirmation from basic and clinical real-world studies. Future research should also include genetic and metabolomic data related to GERD related diseases. For example, non erosive reflux disease, reflux esophagitis, BE, and hiatal hernia. At the same time, it is necessary to compare the genetic and metabolomic differences among various diseases, which will help clarify the relationship between diseases and better explain GERD.