Antibiotic Therapy and the Gut Microbiome: Investigating the Effect of Delivery Route on Gut Pathogens

Stephen A Kelly, Jonathan Nzakizwanayo, Aoife M Rodgers, Li Zhao, Rebecca Weiser, Ismaiel A Tekko, Helen O McCarthy, Rebecca J Ingram, Brian V Jones, Ryan F Donnelly, Brendan F Gilmore

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The contribution of the gut microbiome to human health has long been established, with normal gut microbiota conferring protection against invasive pathogens. Antibiotics can disrupt the microbial balance of the gut, resulting in disease and the development of antimicrobial resistance. The effect of antibiotic administration route on gut dysbiosis remains under-studied to date, with conflicting evidence on the differential effects of oral and parenteral delivery. We have profiled the rat gut microbiome following treatment with commonly prescribed antibiotics (amoxicillin and levofloxacin), via either oral or intravenous administration. Fecal pellets were collected over a 13-day period and bacterial populations were analyzed by 16S rRNA gene sequencing. Significant dysbiosis was observed in all treatment groups, regardless of administration route. More profound dysbiotic effects were observed following amoxicillin treatment than those with levofloxacin, with population richness and diversity significantly reduced, regardless of delivery route. The effect on specific taxonomic groups was assessed, revealing significant disruption following treatment with both antibiotics. Enrichment of a number of groups containing known gut pathogens was observed, in particular, with amoxicillin, such as the family Enterobacteriaceae. Depletion of other commensal groups was also observed. The degree of dysbiosis was significantly reduced toward the end of the sampling period, as bacterial populations began to return to pretreatment composition. Richness and diversity levels appeared to return to pretreatment levels more quickly in intravenous groups, suggesting convenient parenteral delivery systems may have a role to play in reducing longer term gut dysbiosis in the treatment of infection.

Original languageEnglish
Pages (from-to)1283–1296
Number of pages14
JournalACS infectious diseases
Issue number5
Early online date12 Apr 2021
Publication statusPublished - 14 May 2021

Bibliographical note

Funding Information:
This work was supported by the Wellcome Trust through grant UNS39792.

Publisher Copyright:
© 2021 American Chemical Society.


  • antibiotic
  • dysbiosis
  • gut
  • microbiome
  • pathogen
  • route of administration

ASJC Scopus subject areas

  • Infectious Diseases


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