Differential response to prolonged amoxicillin treatment: long-term resilience of the microbiome versus long-lasting perturbations in the gut resistome

Abstract

The 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.

Ecological consequences of low ampicillin concentrations on an ex-vivo biofilm model of the human oral microbiome

“…However, most available studies using metagenomics have focused on the gut resistome. In these studies, the reported outcomes on the resistome vary from no signi cant effects to increased antibiotic resistance gene load and diversity following antibiotic therapy (20,(70)(71)(72). For the oral microbiome, our knowledge is mostly restricted to a few studies indicating that the oral microbiome is more resilient to changes than the gut microbiome (19,20).…”

Strategies for applying probiotics in the antibiotic management of Clostridioides difficile infection

“…The baseline host gut microbiota is influenced by a variety of factors including geographic location, diet, gender, age, drug therapy, host immunity, and disease. 84,[113][114][115][116][117][118][119] The abundance of Bifidobacterium spp. and Blautia spp.…”

“…130,131 Dhariwal et al found that amoxicillin treatment significantly reduced the proportion of health-related short-chain fatty acid-producing microbes in the host gut. 84 Cruz-Lebron et al found that chronic opioid use, which is widespread in the United States, caused severe intestinal dysfunction, with serious disruptions to host gut microbiota, intestinal bacterial metabolic profiles, and gut barrier integrity. 87 Hayase et al found that disruption of the baseline microbiota directly affected the antitumor efficacy of immune checkpoint inhibitors (ICIs).…”

“…53 (3) Rebuilding the gut ecological balance and nutritional environment: one of the main reasons why pCDI gradually becomes rCDI is because initial antibiotic treatment causes a great disturbance and damage to the host gut environment, especially dramatic changes to the gut nutritional environment and the gut microbiome, laying the groundwork for reinfection and the outbreak of C. difficile and its accompanying microbes. 9,27,84 Dudzicz et al found that continuous intake of Lactobacillus plantarum 299v during antibiotic therapy (for patients who were receiving immunosuppressive drugs) was effective at preventing the development of CDI. 85 Korpela et al found that the daily intake of probiotics by infants during antibiotic treatment and for 3 weeks after treatment contributed to the restoration of the normal structure of the microbiota.…”

The impact of antibiotic exposure on antibiotic resistance gene dynamics in the gut microbiota of inflammatory bowel disease patients

“…The gut microbiota is not only a sophisticated ecosystem, but also an important reservoir of antibiotics resistance genes (ARGs) ( Hu et al, 2013 ; Hofer, 2022 ). Several metagenomic analyses have revealed that the structure of the gut microbiota is markedly influenced by these resistance genes ( Dhariwal et al, 2023 ), with a shared network of ARGs existing between pathogenic and commensal gut microorganisms ( Forster et al, 2022 ). In order to solve the increasingly severe problem of drug resistance, we must understand how bacteria acquire and disseminate resistance genes in clinical settings.…”