Causal Relationship Between Butyrate and Dyspepsia: Evidence From Two-Sample Mendelian Randomization Analysis of CSF...

Area of Science:

• Neuroscience
• Gastroenterology
• Metabolomics

Background:

• Dyspepsia is a common gastrointestinal disorder with complex causes, potentially involving the gut-brain axis.
• The role of central nervous system metabolites in cerebrospinal fluid (CSF) for dyspepsia is not well understood.

Purpose of the Study:

• To explore the potential causal link between CSF metabolites and dyspepsia.
• Utilize a two-sample Mendelian randomization (MR) approach to investigate this relationship.

Main Methods:

• Conducted a two-sample MR analysis using genome-wide association study (GWAS) data.
• Analyzed CSF metabolite data from 532 individuals and dyspepsia data from UK Biobank (7586 cases, 353,608 controls).
• Employed inverse-variance weighted (IVW) method and sensitivity analyses to ensure result robustness.

Main Results:

• Elevated CSF butyrate demonstrated a significant inverse causal association with dyspepsia (IVW OR=0.997, p<0.001).
• Sensitivity analyses confirmed no significant heterogeneity or pleiotropy.
• Enrichment analysis indicated involvement of genes related to serine-type peptidase and protein catabolism.

Conclusions:

• This study provides novel genetic evidence connecting higher CSF butyrate levels to a reduced risk of dyspepsia.
• Suggests a potential neuroprotective function of butyrate within the gut-brain axis.