Long-Term Use of Amoxicillin Is Associated with Changes in Gene Expression and DNA Methylation in Patients with Low...

Area of Science:

• Molecular biology
• Genomics
• Microbiome research

Background:

• Long-term antibiotic use is increasing for conditions like low back pain with Modic changes.
• The molecular consequences of prolonged antibiotic therapy remain largely unknown.
• Investigating these effects is crucial for understanding treatment safety and efficacy.

Purpose of the Study:

• To investigate the longitudinal molecular impact of 100-day amoxicillin treatment versus placebo on gene expression and DNA methylation.
• To identify changes in transcriptome and epigenome in patients with Modic changes.
• To assess the persistence of these molecular alterations post-treatment.

Main Methods:

• Longitudinal transcriptome and epigenome-wide analyses in 100 patients over 100 days of amoxicillin or placebo.
• Genome-wide gene expression and DNA methylation profiling at screening, day 100, and one-year follow-up.
• Intra-individual analysis to track changes within patients.

Main Results:

• Amoxicillin treatment led to significant intra-individual changes in gene expression and DNA methylation, unlike placebo.
• 28 genes were differentially expressed after 100 days, including downregulated immunoglobulin genes.
• Significant DNA methylation changes (4548 CpGs) were observed, primarily increased methylation post-treatment, with lasting effects on gene expression.

Conclusions:

• Long-term amoxicillin treatment induces significant, lasting molecular alterations in gene expression and DNA methylation.
• These changes suggest unrecognized side effects of prolonged antibiotic use.
• Further research is needed to understand the clinical implications of these persistent molecular changes.