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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 pl...

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Autores principales: 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
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10376514/
https://www.ncbi.nlm.nih.gov/pubmed/37508313
http://dx.doi.org/10.3390/antibiotics12071217
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author 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
author_facet 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
author_sort Vigeland, Maria Dehli
collection PubMed
description 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.
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spelling pubmed-103765142023-07-29 Long-Term Use of Amoxicillin Is Associated with Changes in Gene Expression and DNA Methylation in Patients with Low Back Pain and Modic Changes 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 Antibiotics (Basel) Article 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. MDPI 2023-07-21 /pmc/articles/PMC10376514/ /pubmed/37508313 http://dx.doi.org/10.3390/antibiotics12071217 Text en © 2023 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
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
Long-Term Use of Amoxicillin Is Associated with Changes in Gene Expression and DNA Methylation in Patients with Low Back Pain and Modic Changes
title Long-Term Use of Amoxicillin Is Associated with Changes in Gene Expression and DNA Methylation in Patients with Low Back Pain and Modic Changes
title_full Long-Term Use of Amoxicillin Is Associated with Changes in Gene Expression and DNA Methylation in Patients with Low Back Pain and Modic Changes
title_fullStr Long-Term Use of Amoxicillin Is Associated with Changes in Gene Expression and DNA Methylation in Patients with Low Back Pain and Modic Changes
title_full_unstemmed Long-Term Use of Amoxicillin Is Associated with Changes in Gene Expression and DNA Methylation in Patients with Low Back Pain and Modic Changes
title_short Long-Term Use of Amoxicillin Is Associated with Changes in Gene Expression and DNA Methylation in Patients with Low Back Pain and Modic Changes
title_sort long-term use of amoxicillin is associated with changes in gene expression and dna methylation in patients with low back pain and modic changes
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10376514/
https://www.ncbi.nlm.nih.gov/pubmed/37508313
http://dx.doi.org/10.3390/antibiotics12071217
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