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

Long-term antibiotics are prescribed for a variety of medical conditions, recently including low back pain with Modic changes. The molecular impact of such treatment is unknown. We conducted longitudinal transcriptome and epigenome analyses in patients (n = 100) receiving amoxicillin treatment or placebo for 100 days in the Antibiotics in Modic Changes (AIM) study. Gene expression and DNA methylation were investigated at a genome-wide level at screening, after 100 days of treatment, and at one-year follow-up. We identified intra-individual longitudinal changes in gene expression and DNA methylation in patients receiving amoxicillin, while few changes were observed in patients receiving placebo. After 100 days of amoxicillin treatment, 28 genes were significantly differentially expressed, including the downregulation of 19 immunoglobulin genes. At one-year follow-up, the expression levels were still not completely restored. The significant changes in DNA methylation (n = 4548 CpGs) were mainly increased methylation levels between 100 days and one-year follow-up. Hence, the effects on gene expression occurred predominantly during treatment, while the effects on DNA methylation occurred after treatment. In conclusion, unrecognized side effects of long-term amoxicillin treatment were revealed, as alterations were observed in both gene expression and DNA methylation that lasted long after the end of treatment.

Automated summary

Long-term use of antibiotics has a lasting impact on gene expression and DNA methylation, leading to potential side effects. This study found that patients receiving amoxicillin treatment for 100 days showed changes in gene expression and DNA methylation, while placebo group showed minimal changes. After 100 days, 28 genes, including 19 immunoglobulin genes, were significantly differentially expressed. These expression levels were still not completely restored at one-year follow-up. Significant changes in DNA methylation mainly occurred between 100 days and one-year follow-up. Hence, long-term amoxicillin treatment can result in lasting alterations in both gene expression and DNA methylation.