IADR Abstract Archives
Impact of Long-Term Amoxicillin Treatment on the Gut Microbiome and Resistome
Objectives: The collateral impact of antibiotics on the microbiome has lately attained increasing attention. However, the knowledge of ecological consequences of long-term antibiotic exposure on the gut microbiome, including the development and persistence of antibiotic resistance, is still limited. Here, we aim to investigate the effects of long-term exposure of the most commonly used antibiotic (amoxicillin) on the gut microbiome and resistome.
Methods: Fecal samples were collected from 20 patients receiving 100 days of amoxicillin 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 the administration of antibiotics or placebo. Whole metagenomic shotgun sequencing and functional metagenomics sequencing data were utilized to characterize the abundance and diversity of microbial and resistome composition.
Results: While the microbiome profiles of placebo subjects were relatively stable over time, significant changes in the diversity and overall microbiome composition were observed upon amoxicillin treatment. In particular, health-associated short-chain fatty acids producing species significantly decreased in proportion. However, these changes were short-lived as the gut microbiota showed recovery to baseline levels 9 months post-treatment. On the other hand, exposure to long-term antibiotics was associated with an increase in total antimicrobial resistance load and diversity of antimicrobial resistance genes, which remained statistically significant even at 12 months compared to the placebo group. Additionally, these long-lasting changes were more targeted to the antibiotic treatment as the beta-lactamase resistance genes were significantly enriched in response to amoxicillin. Although the antibiotic altered the resistome composition, the impact of amoxicillin remained specific to individual subjects.
Conclusions: Overall, our results suggested that the impact of prolonged amoxicillin exposure was more pronounced and long-lasting in the fecal resistome rather than in microbiome composition. Such information is relevant for designing rational administration guidelines for antibiotic therapies.
Methods: Fecal samples were collected from 20 patients receiving 100 days of amoxicillin 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 the administration of antibiotics or placebo. Whole metagenomic shotgun sequencing and functional metagenomics sequencing data were utilized to characterize the abundance and diversity of microbial and resistome composition.
Results: While the microbiome profiles of placebo subjects were relatively stable over time, significant changes in the diversity and overall microbiome composition were observed upon amoxicillin treatment. In particular, health-associated short-chain fatty acids producing species significantly decreased in proportion. However, these changes were short-lived as the gut microbiota showed recovery to baseline levels 9 months post-treatment. On the other hand, exposure to long-term antibiotics was associated with an increase in total antimicrobial resistance load and diversity of antimicrobial resistance genes, which remained statistically significant even at 12 months compared to the placebo group. Additionally, these long-lasting changes were more targeted to the antibiotic treatment as the beta-lactamase resistance genes were significantly enriched in response to amoxicillin. Although the antibiotic altered the resistome composition, the impact of amoxicillin remained specific to individual subjects.
Conclusions: Overall, our results suggested that the impact of prolonged amoxicillin exposure was more pronounced and long-lasting in the fecal resistome rather than in microbiome composition. Such information is relevant for designing rational administration guidelines for antibiotic therapies.