Temporal Development And Potential Interactions Between The Gut Microbiome And Resistome In Early Childhood

Background:Antibiotics are important drugs to protect human life and improve livestock production.However,in recent years,due to irrational or inappropriate use of antibiotics,antibiotic-resistant bacteria have gradually emerged and increased,and infections related to antimicrobial resistance(AMR)have become a major threat to global health.It is important to note that the proportion of children treated with antibiotics is increasing year by year and there is no standardized treatment plan.As a "super organ" throughout life,the human gut microbiome plays a key role in human health and disease,especially during infancy.At the same time,the gut microbiome is a major reservoir of antibiotic resistance genes(ARGs).Early antibiotic exposure not only reduced the diversity of intestinal microbiome in infants,but also significantly increased the diversity and richness of ARGs in infants.Early antibiotic exposure and early antibiotic-resistant bacterial infections greatly affect the health and subsequent development of children.However,although infant gut microbes are a dynamic development process,previous studies on infant gut microbes mainly focus on cross-sectional changes or changes in a relatively short period of time,and rarely pay attention to longitudinal changes in infant gut antibiotic resistome.The temporal dynamic development of early childhood gut antibiotic resistome and its influencing factors are still unclear.The interaction between the gut microbiome and the antibiotic resistome still needs to be further explored.Method:Metagenomic sequencing data from the DIABIMMUNE cohort study and corresponding clinical metadata were used in this study.PLdist analysis was used to calculate the Bray-Curtis distance index of gut antibiotic resistome and the taxonomy of microbiome,and PERMANOVA was used to examine the effect of antibiotic use or not on the microbiome and gut antibiotic resistome.The effects of antibiotic use on the abundance of the overall microbial community and bacteria containing specific ARGs were observed in vitro experiments.The median Jaccard similarity index of the two groups was analyzed by Wilcoxon rank sum test or t-test to assess the effect of antibiotic use on the stability of the gut microbiome and antibiotic resistome.By using Maaslin2 analysis to screen different bacteria,microbial networks related to influencing factors were constructed.Mediation analysis determined that antibiotic use affects Immunoglobulin E(IgE)levels in children through gut microbiome.Results:In this study,deep metagenomic sequencing data from 212 children,including multiple time point samples from 0 to 3 years old,were used to comprehensively analyze the phase-specific patterns and factors affecting the gut microbiome and the gut antibiotic resistome,and to analyze and visualize the longitudinal patterns of the gut microbiome and the gut antibiotic resistome.The results showed that:(1)Antibiotic treatment caused changes in β-diversity and instability of gut microbiome and the gut antibiotic resistome;(2)Antibiotic treatment had a greater effect on the gut antibiotic resistome than the microbiome;(3)There were different core microorganisms that affected the composition of gut antibiotic resistome at different stages;(4)The richness and abundance of ARGs in bacteria of different phyla changed with age;(5)First exposure to antibiotics resulted in a sharp increase in the number of opportunistic pathogens carrying genes encoding multidrug effector pumps;(6)Multiple factors may affect the formation of the gut microbiome and antibiotic resistome.The consumption of vegetables and whole grains was significantly negatively correlated with the abundance of ARGs,while significantly positively correlated with the abundance of beneficial bacteria.Conclusion:The multifaceted analysis of gut microbiome and antibiotic resistome in early childhood demonstrates that antibiotic disrupts community stability of both,and illustrates the structural composition of the gut antibiotic resistome varies at different stages under the influence of different core-microorganisms.The data may provide new insights into early life research.