Association between antibiotics and gut microbiome dysbiosis in children: systematic review and meta-analysis

Abstract

Antibiotics in childhood have been linked with diseases including asthma, juvenile arthritis, type 1 diabetes, Crohn's disease and mental illness. The underlying mechanisms are thought related to dysbiosis of the gut microbiome. We conducted a systematic review of the association between antibiotics and disruption of the pediatric gut microbiome. Searches used MEDLINE, EMBASE and Web of Science. Eligible studies: association between antibiotics and gut microbiome dysbiosis; children 0-18 years; molecular techniques of assessment; outcomes of microbiome richness, diversity or composition. Quality assessed by Newcastle-Ottawa Scale or Cochrane Risk of Bias Tool. Meta-analysis where possible. A total of 4,668 publications identified: 12 in final analysis (5 randomized controlled trials (RCTs), 5 cohort studies, 2 cross-sectional studies). Microbiome richness was measured in 3 studies, species diversity in 6, and species composition in 10. Quality of evidence was good or fair. 5 studies found a significant reduction in diversity and 3 a significant reduction in richness. Macrolide exposure was associated with reduced richness for twice as long as penicillin. Significant reductions were seen in Bifidobacteria (5 studies) and Lactobacillus (2 studies), and significant increases in Proteobacteria such as E. coli (4 studies). A meta-analysis of RCTs of the effect of macrolide (azithromycin) exposure on the gut microbiome found a significant reduction in alpha-diversity (Shannon index: mean difference −0.86 (95% CI −1.59, −0.13). Antibiotic exposure was associated with reduced microbiome diversity and richness, and with changes in bacterial abundance. The potential for dysbiosis in the microbiome should be taken into account when prescribing antibiotics for children.Systematic review registration number: CRD42018094188ARTICLE HISTORY

The composition of the gut microbiota following early-life antibiotic exposure affects host health and longevity in later life

“…Antibioticexposed mice were colonized by two compositionally and functionally distinct low-diversity microbiota (which we termed PAM I and PAM II mice) despite the fact that these were littermates exposed to the same antibiotics. The effects of antibiotic exposure we observed are consistent with the effects reported previously by us and others in mice (Lynn et al, 2018;Ng et al, 2019) and humans (Bokulich et al, 2016;McDonnell et al, 2021;Dethlefsen and Relman, 2011;Hildebrand et al, 2019;Palleja et al, 2018). The importance of different patterns of recolonization following antibiotic exposure on immunity and metabolism in later life are currently poorly understood.…”

“…These pathways included a range of bacterial metabolic pathways, including several involved in SCFA fermentation . The effects of antibiotic exposure we observed, including a significant loss of diversity, blooms of enterobacteria and other pathobionts, and inter-individual/cage variation in the response of the gut microbiota to antibiotics, are consistent with the effects reported previously by us and others in mice (Lynn et al, 2018;Ng et al, 2019) and humans (Bokulich et al, 2016;McDonnell et al, 2021;Dethlefsen and Relman, 2011;Hildebrand et al, 2019;Palleja et al, 2018). We hypothesized that different low-diversity microbiota community types that colonize the gut following antibiotic exposure would differentially affect immunity and metabolism in later life, potentially influencing overall lifespan.…”

Oral iron supplementation after antibiotic exposure induces a deleterious recovery of the gut microbiota

“…Perturbations in the gut microbiota may lead to disturbed microbial homeostasis, a state termed dysbiosis. Antibiotic treatments are among the strongest inducers of gut dysbiosis [ 2 , 3 ]. Antibiotics are routinely administered to treat active infections or for prophylaxis prior to invasive endoscopic or surgical interventions [ 4 ].…”

Impact of antibiotics to off-target infant gut microbiota and resistance genes in cohort studies

“…Previous studies have found mixed results associating diversity and antibiotic exposure depending on geography, age of the child, type of antibiotic prescribed, and time since antibiotic exposure, but, generally, antibiotic exposures are associated with stable or decreased withinsample diversity 44 . Consistently, we found NHBCS infants had a statistically significantly (pvalue < 0.05) higher alpha diversity than samples in the DIABIMMUNE Study.…”