Vigeland Maria Dehli, Flåm Siri Tennebø, Vigeland Magnus Dehli, Espeland Ansgar, Zucknick Manuela, Wigemyr Monica, Bråten Lars Christian Haugli, Gjefsen Elisabeth, Zwart John-Anker, Storheim Kjersti, Pedersen Linda Margareth, Selmer Kaja, Lie Benedicte Alexandra, Gervin Kristina
Department of Research, Innovation and Education, Division of Clinical Neuroscience, Oslo University Hospital, 0450 Oslo, Norway.
Faculty of Medicine, University of Oslo, 0313 Oslo, Norway.
Antibiotics (Basel). 2023 Jul 21;12(7):1217. doi: 10.3390/antibiotics12071217.
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 ( = 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 ( = 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.
长期抗生素被用于多种医疗状况，最近还包括伴有Modic改变的下背痛。这种治疗的分子影响尚不清楚。在“Modic改变中的抗生素”（AIM）研究中，我们对100名接受阿莫西林治疗或安慰剂治疗100天的患者进行了纵向转录组和表观基因组分析。在筛查时、治疗100天后以及一年随访时，在全基因组水平上研究基因表达和DNA甲基化。我们发现接受阿莫西林治疗的患者个体内基因表达和DNA甲基化存在纵向变化，而接受安慰剂治疗的患者几乎没有变化。阿莫西林治疗100天后，有28个基因显著差异表达，包括19个免疫球蛋白基因的下调。在一年随访时，表达水平仍未完全恢复。DNA甲基化的显著变化（4548个CpG位点）主要是在100天至一年随访期间甲基化水平升高。因此，对基因表达的影响主要发生在治疗期间，而对DNA甲基化的影响发生在治疗后。总之，长期阿莫西林治疗存在未被认识到的副作用，因为在治疗结束后很长时间，基因表达和DNA甲基化都出现了改变。
