Frontiers in Pediatrics (Jun 2021)

Low-Dose Antibiotic Prophylaxis Induces Rapid Modifications of the Gut Microbiota in Infants With Vesicoureteral Reflux

  • William Morello,
  • Federica D'Amico,
  • Jessica Serafinelli,
  • Silvia Turroni,
  • Isabella Abati,
  • Jessica Fiori,
  • Esra Baskin,
  • Fatos Yalcinkaya,
  • Augustina Jankauskiene,
  • Marco Pennesi,
  • Aleksandra Zurowska,
  • Francesca Becherucci,
  • Dorota Drozdz,
  • Djalila Mekahli,
  • Djalila Mekahli,
  • Grazyna Krzemien,
  • Claudio La Scola,
  • Katarzyna Taranta-Janusz,
  • Otto Mehls,
  • Franz Schaefer,
  • Marco Candela,
  • Giovanni Montini,
  • Giovanni Montini

DOI
https://doi.org/10.3389/fped.2021.674716
Journal volume & issue
Vol. 9

Abstract

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Background and Objectives: Maturation of the gut microbiota (GM) in infants is critically affected by environmental factors, with potential long-lasting clinical consequences. Continuous low-dose antibiotic prophylaxis (CAP) is the standard of care for children with vesicoureteral reflux (VUR), in order to prevent recurrent urinary tract infections. We aimed to assess short-term GM modifications induced by CAP in infants.Methods: We analyzed the GM structure in 87 infants (aged 1-5 months) with high-grade VUR, previously exposed or naïve to CAP. Microbial DNA was extracted from stool samples. GM profiling was achieved by 16S rRNA gene-based next-generation sequencing. Fecal levels of short- and branched-chain fatty acids were also assessed.Results: 36/87 patients had been taking daily CAP for a median time of 47 days, while 51/87 had not. In all patients, the GM was predominantly composed by Bifidobacteriaceae and Enterobacteriaceae. Subgroup comparative analysis revealed alterations in the GM composition of CAP-exposed infants at phylum, family and genus level. CAP-exposed GM was enriched in members of Enterobacteriaceae and Bacteroidetes, especially in the genera Bacteroides and Parabacteroides, and showed a trend toward increased Klebsiella, often associated with antibiotic resistance. In contrast, the GM of non-CAP children was mostly enriched in Bifidobacterium. No differences were found in fatty acid levels.Conclusions: In infants with VUR, even a short exposure to CAP definitely alters the GM composition, with increased relative abundance of opportunistic pathogens and decreased proportions of health-promoting taxa. Early low-dose antibiotic exposure might bear potential long-term clinical risks.

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