Metagenomic Analysis Reveals the Distribution of Antibiotic Resistance Genes in a Large-Scale Population of Healthy Individuals and Patients With Varied Diseases

Abstract

The human gut microbiome is a reservoir for antibiotic resistance gene (ARG). Therefore, characterizing resistome distribution and potential disease markers can help manage antibiotics at the clinical level. While much population-level research has highlighted the strong effect of donor geographic origin on ARG prevalence in the human gut, little is known regarding the effects of other properties, such as age, sex, and disease. Here we employed 2,037 fecal metagenomes from 12 countries. By quantifying the known resistance genes for 24 types of antibiotics in each community, we showed that tetracycline, aminoglycoside, beta-lactam, macrolide-lincosamide-streptogramin (MLS), and vancomycin resistance genes were the dominant ARG types in the human gut. We then compared the ARG profiles of 1427 healthy individuals from the 2,037 samples and observed significant differences across countries. This was consistent with expectations that regional antibiotic usage and exposure in medical and food production contexts affect distribution. Although no specific uniform pattern of ARG was observed, a significant increase in resistance potential among multiple disease groups implied that the disease condition may be another source of ARG variance. In particular, the cooccurrence pattern of some enriched bacterial species and ARGs that were obtained in type 2 diabetes (T2D) and liver cirrhosis patients implied that some disease-associated species may be potential hosts of enriched ARGs, which could be potential biomarkers for the prediction and intervention of such diseases. Overall, our study identifies factors associated with the human gut resistome, including substantial effects of region and heterogeneous effects of disease status, and highlights the value of ARG analysis in disease research and clinical applications.

Microbiomes and Resistomes in Biopsy Tissue and Intestinal Lavage Fluid of Colorectal Cancer

“…Our results reveal that the common ARGs, detected in both IVF and tissue, confer multidrug resistance, as well as resistance to aminoglycosides, beta-lactams, and tetracycline antibiotics. A previous study showed that tetracycline, aminoglycoside, beta-lactam, MLS, vancomycin, and multidrug resistance genes are the dominant types in the human gut (Qiu et al, 2020). The human microbiome may constitute a mobilizable reservoir of ARGs, which are accessible to pathogenic bacteria for acquiring antibiotic resistance.…”

“…Most ARGs in the human gut are those resistant to widely used antibiotics, and antibiotic therapy leads to personalized resistome diversification and individual-specific strain level selection in the gut microbiota (Li et al, 2019). Analysis of ARG distribution in the population provides an important indicator for public health policies (Qiu et al, 2020).…”

Good microbes, bad genes? The dissemination of antimicrobial resistance in the human microbiome

“… 23 Diseases connected to gut inflammation have also been observed to lead to an expansion of the intestinal resistome, including type 2 diabetes, cirrhosis, obesity, and IBD. 7 , 24 , 57 A common mechanism of increased ARG prevalence across these diseases is likely the blooming of ARG-enriched taxa such as the Enterobacterales in response to a dysbiotic state. 58 Dietary and therapeutic interventions that reduce the abundance of Enterobacterales could therefore beneficially modulate the resistome.…”

Analysis of Gut Microbiota Signature and Microbe-Disease Progression Associations in Locally Advanced Non-Small Cell Lung Cancer Patients Treated With Concurrent Chemoradiotherapy

“…Bacteria enriched in Ermf genes had resistance of macrolide, lincosamide, and streptogramin, while microbiota enriched in Vanug , Vanwg , and Vanrd had vancomycin resistance. The metagenomic analysis of antibiotic resistome in a large-scale healthy human demonstrated that Chinese population harbored the most abundant ARGs, and Ermf could be representative ARGs of the Chinese population ( Qiu et al., 2020 ). Except for antibiotics abuse, ARGs could be transferred horizontally through bacteria from food and animals, which means ARGs could be obtained through various ways such as the transmission of food chain ( Kumar et al., 2020 ).…”