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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.

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