by Earlham Institute
Two distinct clusters apparent in the global landscape of adult gut resistome profiles. a NMDS projection of Bray–Curtis dissimilarities among the log-transformed ARG family profiles (cpg) in adult gut metagenomes (contours estimate sample densities). Samples were colored by cluster assignment (PAM, Bray-Curtis clustering, k=2). b Average silhouette width of PAM Bray-Curtis clusters as a function of cluster number k. c Sample density projecting points onto the line joining cluster medoids using Bray–Curtis dissimilarities. d Box plots of the summed abundance of ARGs in each antibiotic class, separated by resistotype (`background’ or `FAMP’) with the distribution of total ARGs (cpg) by resistotype shown at the bottom. e Relative abundances of the ten species with highest mean fold difference between resistotypes and two-sided Mann–Whitney test, Benjamini–Hochberg-adjusted p < 0.05. Statistics on the differential abundance of ARG classes and the species between the two resistotypes are provided in Table S7. Results from clustering the ARG profiles with alternative methods and clustering of species compositions are given in Fig. S8. Comparison of species diversity and ARG diversity between the background and the FAMP resistotypes is provided in Fig. S5. Naming of the FAMP resistotype reflects the five antibiotic resistance classes enriched with the largest fold differences: F, fluoroquinolone and fosfomycin; A, aminoglycoside; M, multi-drug; P, peptide. Number of metagenome samples n = 3034 for the background resistotype, n = 2338 for the FAMP resistotype. In the box plots, the box spans from 25th to 75th percentiles, the line inside the box is the median, and the whisker spans from the minimum to the maximum values. Credit: Nature Communications (2023). DOI: 10.1038/s41467-023-36633-7
The community of microbes living in and on our bodies may be acting as a reservoir for antibiotic resistance, according to new research from the Earlham Institute and Quadram Institute in Norwich. The work is published in the journal Nature Communications.
The use of antibiotics leads to “collateral damage” to the microbiome, ramping up the number of resistance genes being passed back and forth between strains in the microbiome. The findings also suggest these genes spread so easily through a population, that regardless of your own health and habits, the number of resistance genes in your gut is heavily influenced by national trends in antibiotic consumption.
The rise of antimicrobial resistance (AMR) among human pathogens is widely seen as one of the most serious threats to global health in the coming decades. AMR is already believed to be contributing to tens of thousands of deaths in Europe each year.
Tracking the emergence and spread of genes that help these pathogens to shrug off antibiotics has generally been limited to samples taken from infected individuals. The majority of microbes living in the human body, however, are not pathogenic.
The human microbiome is a complex and dynamic community of millions of species of microbes, primarily living in the gut and coexisting with us. Microbiomes play an important role in health and disease, with the gut microbiome known to help with the digestion of food and the development of our immune system.
Professor Chris Quince, author of the research at the Earlham Institute and Quadram Institute, said, “Even a healthy individual who hasn’t taken antibiotics recently is constantly bombarded by microbes from people or even pets they interact with, which leads to resistance genes becoming embedded in their own microbiota. If they exist in a population with a heavy burden of antibiotic consumption, it leads to more resistance genes in their microbiome.”
To better understand the impact of antimicrobials on the gut microbiome, researchers at the Earlham Institute and Quadram Institute in Norwich, together with collaborators in the Republic of Korea, analyzed over 3,000 gut microbiome samples, collected from healthy individuals across 14 countries.
They then compared the resistance genes identified in samples to those found in large genome collections in order to understand the movement of AMR genes between microbe and pathogen species.
“We deliberately focused on samples from healthy people, or at least those we could be confident weren’t taking antibiotics,” explained Professor Quince. “We needed to see the gene profile in the gut microbiome without the influence of any antimicrobials.”
They carefully catalogued and recorded the number of antimicrobial resistance genes found in the samples by comparing data to the Comprehensive Antibiotic Resistance Database, a public health resource where resistance genes are documented.
The team identified a median of 16 AMR genes per stool sample analyzed. They also found that the median number of genes varied across the 14 countries for which they had data. For example, they saw a five-fold variation in median resistance levels between the lowest in the Netherlands and the highest in Spain.
Using World Health Organization and ResistanceMap data, the team were able to show a strong correlation between the frequency of resistance genes present in a country and national antibiotic consumption levels.
“We found that in countries where antibiotics are taken more regularly, their populations also have higher numbers of resistance genes in their gut microbiome,” said Professor Quince.
The reason this collateral damage is such a major problem is that microbes are constantly sharing genes with each other. Known as horizontal gene transfer, this process helps AMR genes to spread back and forth between species.
“Our bodies are continually importing and exporting microbes and pathogen strains,” explained Professor Quince. “These strains are themselves passing genes back and forth, which means the challenge of AMR has to be tackled at both the micro and macro level. Given our complex relationship with microbes, we need to do more research to understand how we maximize the benefits and minimize the risks when it comes to guiding treatment decisions and developing new medicines.”
Professor Falk Hildebrand, research author at the Quadram Institute and Earlham Institute, said, “We’ve known for some years that antimicrobial resistance genes can spread incredibly fast between gut bacteria. This study is so important because it can, for the first time, quantify the impact national antibiotic usage has on our commensal bacteria, as well as giving us insights into the common types of resistance we can expect to evolve.”
The researchers plan to carry out further research—and encourage others to—in order to investigate the relationship in more countries and inform public health strategies.
Samples studied came from Austria, Canada, China, Germany, Denmark, Spain, France, Israel, Italy, Kazakhstan, Madagascar, Netherlands, Sweden, and the U.S..
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