Abstract

Antibiotic resistance in bacteria has become a major global health problem. One of the main reservoirs of antibiotic resistance genes is the human gut microbiota. To characterise these genes, a metagenomic approach was used. In this study, a comprehensive antibiotic resistome catalog was established using fecal samples from 246 healthy individuals from world’s longevity township in Jiaoling, China. In total, 606 antibiotic resistance genes were detected. Our results indicated that antibiotic resistance genes in the human gut microbiota accumulate and become more complex with age as older groups harbour the highest abundance of these genes. Tetracycline resistance gene type tetQ was the most abundant group of antibiotic resistance genes in gut microbiota, and the main carrier of antibiotic resistance genes was Bacteroides. Antibiotic efflux, inactivation, and target alteration were found to be the dominant antimicrobial resistance mechanisms. This research may help to establish a comprehensive antibiotic resistance catalog that includes extremely long-lived healthy people such as centenarians, and may provide potential recommendations for controlling the use of antibiotics.

Highlights

  • Since the discovery of penicillin in 1929 [1], antibiotic resistance in bacteria has become an increasing threat to human health and a global health problem [2]

  • Just as the human microbiome can constitute a mobile antibiotic resistance genes (ARG) reservoir, pathogens can use these genes to obtain antibiotic resistance through gene transfer [30]. Reference databases such as the Antibiotic Resistance Genes Database (ARDB) [31] and the Comprehensive Antibiotic Resistance Database (CARD) [32] have been developed to help researchers investigate ARG, such as those in the intestinal flora of Chinese, Danish, and Spanish populations

  • Our results indicated that ARG in the human gut microbiota accumulate and become more complex with age given that older groups harbour the highest abundance of these genes

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Summary

Introduction

Since the discovery of penicillin in 1929 [1], antibiotic resistance in bacteria has become an increasing threat to human health and a global health problem [2]. The microbiota responds through its own resistance mechanisms, and optimises and spreads antibiotic resistance genes (ARG) through transformation, transfer, and recombination, and forms a colony with antibiotic resistance phenotype [9]. The human gut microbiota is considered to be the reservoir of ARG [18], which can quickly and exchange these genes to spread drug resistance [19]. This presents a high risk of increased antibiotic resistance in human pathogens [20], which has become a serious global public health problem as it renders previously reliable antibiotics ineffective. This study will help establish a comprehensive list of antibiotic resistance in healthy and long-lived people, and provide a useful reference for the management of human ARG

Study Cohort and Sample Collection
DNA Extraction
Metagenomic Sequencing and Data Quality Control
Metagenomic Assembly
Gene Catalog Construction
Analysis of Antibiotic Resistance Genes
Statistical Analysis
Abundance of Antibiotic Resistance Genes Is an Age-Related Cumulative Effect
Representative Resistance Gene Types in Different Age Groups
Representative Types of Antibiotics in Different Age Groups
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