Differential response to prolonged amoxicillin treatment: long-term resilience of the microbiome versus long-lasting perturbations in the gut resistome
ABSTRACTThe collateral impact of antibiotics on the microbiome has attained increasing attention. However, the ecological consequences of long-term antibiotic exposure on the gut microbiome, including antibiotic resistance, are still limited. Here, we investigated long-term exposure effects to amoxi...
| Main Authors: | , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Taylor & Francis Group
2023-12-01
|
| Series: | Gut Microbes |
| Subjects: | |
| Online Access: | https://www.tandfonline.com/doi/10.1080/19490976.2022.2157200 |
| _version_ | 1797236683466342400 |
|---|---|
| author | Achal Dhariwal Lars Christian Haugli Bråten Kjersti Sturød Gabriela Salvadori Ahmed Bargheet Heidi Åmdal Roger Junges Dag Berild John-Anker Zwart Kjersti Storheim Fernanda Cristina Petersen |
| author_facet | Achal Dhariwal Lars Christian Haugli Bråten Kjersti Sturød Gabriela Salvadori Ahmed Bargheet Heidi Åmdal Roger Junges Dag Berild John-Anker Zwart Kjersti Storheim Fernanda Cristina Petersen |
| author_sort | Achal Dhariwal |
| collection | DOAJ |
| description | ABSTRACTThe collateral impact of antibiotics on the microbiome has attained increasing attention. However, the ecological consequences of long-term antibiotic exposure on the gut microbiome, including antibiotic resistance, are still limited. Here, we investigated long-term exposure effects to amoxicillin on the human gut microbiome and resistome. Fecal samples were collected from 20 patients receiving 3-months of amoxicillin or placebo treatment as part of a Norwegian multicenter clinical trial on chronic low back pain (AIM study). Samples were collected at baseline, last day of treatment, and 9 months after antibiotic cessation. The abundance and diversity of microbial and resistome composition were characterized using whole shotgun and functional metagenomic sequencing data. While the microbiome profiles of placebo subjects were stable over time, discernible changes in diversity and overall microbiome composition were observed after amoxicillin treatment. In particular, health-associated short-chain fatty acid producing species significantly decreased in proportion. However, these changes were short-lived as the microbiome showed overall recovery 9 months post-treatment. On the other hand, exposure to long-term amoxicillin was associated with an increase in total antimicrobial resistance gene load and diversity of antimicrobial resistance genes, with persistent changes even at 9 months post-treatment. Additionally, beta-lactam resistance was the most affected antibiotic class, suggesting a targeted response to amoxicillin, although changes at the gene level varied across individuals. Overall, our results suggest that the impact of prolonged amoxicillin exposure was more explicit and long-lasting in the fecal resistome than in microbiome composition. Such information is relevant for designing rational administration guidelines for antibiotic therapies. |
| first_indexed | 2024-03-11T14:20:47Z |
| format | Article |
| id | doaj.art-d6df52edf7ce426d97b3e725a7f1ad65 |
| institution | Directory Open Access Journal |
| issn | 1949-0976 1949-0984 |
| language | English |
| last_indexed | 2024-04-24T17:07:45Z |
| publishDate | 2023-12-01 |
| publisher | Taylor & Francis Group |
| record_format | Article |
| series | Gut Microbes |
| spelling | doaj.art-d6df52edf7ce426d97b3e725a7f1ad652024-03-28T22:38:20ZengTaylor & Francis GroupGut Microbes1949-09761949-09842023-12-0115110.1080/19490976.2022.2157200Differential response to prolonged amoxicillin treatment: long-term resilience of the microbiome versus long-lasting perturbations in the gut resistomeAchal Dhariwal0Lars Christian Haugli Bråten1Kjersti Sturød2Gabriela Salvadori3Ahmed Bargheet4Heidi Åmdal5Roger Junges6Dag Berild7John-Anker Zwart8Kjersti Storheim9Fernanda Cristina Petersen10Institute of Oral Biology, Faculty of Dentistry, University of Oslo, Oslo, NorwayDepartment of Research and Innovation, Division of Clinical Neuroscience, Oslo University Hospital HF, Oslo, NorwayInstitute of Oral Biology, Faculty of Dentistry, University of Oslo, Oslo, NorwayInstitute of Oral Biology, Faculty of Dentistry, University of Oslo, Oslo, NorwayInstitute of Oral Biology, Faculty of Dentistry, University of Oslo, Oslo, NorwayInstitute of Oral Biology, Faculty of Dentistry, University of Oslo, Oslo, NorwayInstitute of Oral Biology, Faculty of Dentistry, University of Oslo, Oslo, NorwayDepartment of Infectious Diseases, Oslo University Hospital HF, Oslo, NorwayDepartment of Research and Innovation, Division of Clinical Neuroscience, Oslo University Hospital HF, Oslo, NorwayDepartment of Research and Innovation, Division of Clinical Neuroscience, Oslo University Hospital HF, Oslo, NorwayInstitute of Oral Biology, Faculty of Dentistry, University of Oslo, Oslo, NorwayABSTRACTThe collateral impact of antibiotics on the microbiome has attained increasing attention. However, the ecological consequences of long-term antibiotic exposure on the gut microbiome, including antibiotic resistance, are still limited. Here, we investigated long-term exposure effects to amoxicillin on the human gut microbiome and resistome. Fecal samples were collected from 20 patients receiving 3-months of amoxicillin or placebo treatment as part of a Norwegian multicenter clinical trial on chronic low back pain (AIM study). Samples were collected at baseline, last day of treatment, and 9 months after antibiotic cessation. The abundance and diversity of microbial and resistome composition were characterized using whole shotgun and functional metagenomic sequencing data. While the microbiome profiles of placebo subjects were stable over time, discernible changes in diversity and overall microbiome composition were observed after amoxicillin treatment. In particular, health-associated short-chain fatty acid producing species significantly decreased in proportion. However, these changes were short-lived as the microbiome showed overall recovery 9 months post-treatment. On the other hand, exposure to long-term amoxicillin was associated with an increase in total antimicrobial resistance gene load and diversity of antimicrobial resistance genes, with persistent changes even at 9 months post-treatment. Additionally, beta-lactam resistance was the most affected antibiotic class, suggesting a targeted response to amoxicillin, although changes at the gene level varied across individuals. Overall, our results suggest that the impact of prolonged amoxicillin exposure was more explicit and long-lasting in the fecal resistome than in microbiome composition. Such information is relevant for designing rational administration guidelines for antibiotic therapies.https://www.tandfonline.com/doi/10.1080/19490976.2022.2157200Antimicrobial resistancemicrobiomeresistomeantimicrobial resistance geneamoxicillinantibiotics |
| spellingShingle | Achal Dhariwal Lars Christian Haugli Bråten Kjersti Sturød Gabriela Salvadori Ahmed Bargheet Heidi Åmdal Roger Junges Dag Berild John-Anker Zwart Kjersti Storheim Fernanda Cristina Petersen Differential response to prolonged amoxicillin treatment: long-term resilience of the microbiome versus long-lasting perturbations in the gut resistome Gut Microbes Antimicrobial resistance microbiome resistome antimicrobial resistance gene amoxicillin antibiotics |
| title | Differential response to prolonged amoxicillin treatment: long-term resilience of the microbiome versus long-lasting perturbations in the gut resistome |
| title_full | Differential response to prolonged amoxicillin treatment: long-term resilience of the microbiome versus long-lasting perturbations in the gut resistome |
| title_fullStr | Differential response to prolonged amoxicillin treatment: long-term resilience of the microbiome versus long-lasting perturbations in the gut resistome |
| title_full_unstemmed | Differential response to prolonged amoxicillin treatment: long-term resilience of the microbiome versus long-lasting perturbations in the gut resistome |
| title_short | Differential response to prolonged amoxicillin treatment: long-term resilience of the microbiome versus long-lasting perturbations in the gut resistome |
| title_sort | differential response to prolonged amoxicillin treatment long term resilience of the microbiome versus long lasting perturbations in the gut resistome |
| topic | Antimicrobial resistance microbiome resistome antimicrobial resistance gene amoxicillin antibiotics |
| url | https://www.tandfonline.com/doi/10.1080/19490976.2022.2157200 |
| work_keys_str_mv | AT achaldhariwal differentialresponsetoprolongedamoxicillintreatmentlongtermresilienceofthemicrobiomeversuslonglastingperturbationsinthegutresistome AT larschristianhauglibraten differentialresponsetoprolongedamoxicillintreatmentlongtermresilienceofthemicrobiomeversuslonglastingperturbationsinthegutresistome AT kjerstisturød differentialresponsetoprolongedamoxicillintreatmentlongtermresilienceofthemicrobiomeversuslonglastingperturbationsinthegutresistome AT gabrielasalvadori differentialresponsetoprolongedamoxicillintreatmentlongtermresilienceofthemicrobiomeversuslonglastingperturbationsinthegutresistome AT ahmedbargheet differentialresponsetoprolongedamoxicillintreatmentlongtermresilienceofthemicrobiomeversuslonglastingperturbationsinthegutresistome AT heidiamdal differentialresponsetoprolongedamoxicillintreatmentlongtermresilienceofthemicrobiomeversuslonglastingperturbationsinthegutresistome AT rogerjunges differentialresponsetoprolongedamoxicillintreatmentlongtermresilienceofthemicrobiomeversuslonglastingperturbationsinthegutresistome AT dagberild differentialresponsetoprolongedamoxicillintreatmentlongtermresilienceofthemicrobiomeversuslonglastingperturbationsinthegutresistome AT johnankerzwart differentialresponsetoprolongedamoxicillintreatmentlongtermresilienceofthemicrobiomeversuslonglastingperturbationsinthegutresistome AT kjerstistorheim differentialresponsetoprolongedamoxicillintreatmentlongtermresilienceofthemicrobiomeversuslonglastingperturbationsinthegutresistome AT fernandacristinapetersen differentialresponsetoprolongedamoxicillintreatmentlongtermresilienceofthemicrobiomeversuslonglastingperturbationsinthegutresistome |