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

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

JOURNAL=Frontiers in Pediatrics

VOLUME=9

YEAR=2021

URL=https://www.frontiersin.org/journals/pediatrics/articles/10.3389/fped.2021.674716

DOI=10.3389/fped.2021.674716

ISSN=2296-2360

ABSTRACT=<p><bold>Background and Objectives:</bold> 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.</p><p><bold>Methods:</bold> 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.</p><p><bold>Results:</bold> 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 <italic>Bifidobacteriaceae</italic> and <italic>Enterobacteriaceae</italic>. 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 <italic>Enterobacteriaceae</italic> and Bacteroidetes, especially in the genera <italic>Bacteroides</italic> and <italic>Parabacteroides</italic>, and showed a trend toward increased <italic>Klebsiella</italic>, often associated with antibiotic resistance. In contrast, the GM of non-CAP children was mostly enriched in <italic>Bifidobacterium</italic>. No differences were found in fatty acid levels.</p><p><bold>Conclusions:</bold> 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.</p>