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

ABSTRACT: 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.

SUBMITTER: Morello W

PROVIDER: S-EPMC8247656 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:Controversy exists regarding the use of continuous antibiotic prophylaxis vs observation in the management of children with vesicoureteral reflux. The reported effectiveness of continuous antibiotic prophylaxis in children with reflux varies widely. We determined whether the aggregated evidence supports use of continuous antibiotic prophylaxis in children with vesicoureteral reflux.We searched the Cochrane Controlled Trials Register, clinicaltrials.gov, MEDLINE(®), EMBASE(®), Google Scholar and recently presented meeting abstracts for reports in any language. Bibliographies of included studies were then hand searched for any missed articles. The study protocol was prospectively registered at PROSPERO (No. CRD42014009639). Reports were assessed and data abstracted in duplicate, with differences resolved by consensus. Risk of bias was assessed using standardized instruments.We identified 1,547 studies, of which 8 are included in the meta-analysis. Pooled results demonstrated that continuous antibiotic prophylaxis significantly reduced the risk of recurrent febrile or symptomatic urinary tract infection (pooled OR 0.63, 95% CI 0.42-0.96) but, if urinary tract infection occurred, increased the risk of antibiotic resistant organism (pooled OR 8.75, 95% CI 3.52-21.73). A decrease in new renal scarring was not associated with continuous antibiotic prophylaxis use. Adverse events were similar between the 2 groups. Significant heterogeneity existed between studies (I(2) 50%, p = 0.03), specifically between those trials with significant risk of bias (eg unclear protocol descriptions and/or lack of blinding).Compared to no treatment, continuous antibiotic prophylaxis significantly reduced the risk of febrile and symptomatic urinary tract infections in children with vesicoureteral reflux, although it increased the risk of infection due to antibiotic resistant bacteria. Continuous antibiotic prophylaxis did not significantly impact the occurrence of new renal scarring or reported adverse events.

Project description:ImportanceInfants with symptomatic Gastroesophageal reflux are treated with pharmacological therapy that includes proton pump inhibitors (PPI) with clinical improvement. The alterations to gut microbiome profiles in comparison to infants without reflux is not known.ObjectiveTo determine the effect of PPI therapy on gut bacterial richness, diversity, and proportions of specific taxa in infants when compared to infants not exposed to acid suppressive therapy.Design setting and participantsThis cohort study was conducted at the Stony Brook Hospital in Stony Brook, NY between February 2016, and June 2019. Infants meeting inclusion criteria were enrolled in a consecutive fashion.ResultsA total of 76 Infants were recruited and 60 were enrolled in the study, Twenty nine infants met clinical criteria for reflux and were treated with PPI therapy: median [IQR] gestation: 38.0 weeks [34.7-39.6 weeks]; median [IQR] birthweight: 2.95 Kg [2.2-3.4]; 14 [46.7%] male) and 29 infant were healthy controls median [IQR] gestation: 39.1 weeks [38-40 weeks]; median [IQR] birthweight: 3.3 Kg [2.2-3.4]; 17 [58.6%] male); 58 stool samples from 58 infants were analyzed. There were differences in Shannon diversity between the reflux and control groups. The reflux group that was exposed to PPI therapy had increased relative abundance of a diverse set of genera belonging to the phylum Firmicutes. On the other hand, the control group microbiota was dominated by Bifidobacterium, and a comparatively lower level of enrichment and abundance of microbial taxa was observed in this group of infants.Conclusions and relevanceWe observed significant differences in both α- and β-diversity of the microbiome, when the two groups of infants were compared. The microbiome in the reflux group had more bacterial taxa and the duration of PPIs exposure was clearly associated with the diversity and abundance of gut microbes. These findings suggest that PPI exposure among infants results in early enrichment of the intestinal microbiome.

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

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