According to recent research from the Earlham Institute and Quadram Institute in Norwich, the community of microbes that reside in and on our bodies may serve as a reservoir for antibiotic resistance.
Antibiotic use causes “collateral damage” to the microbiome, increasing the number of resistance genes that are passed back and forth between strains in the microbiome. The findings also suggest that because these genes spread so easily through a population, the number of resistance genes in your gut is heavily influenced by national trends in antibiotic consumption, regardless of your own health and habits.
Antimicrobial resistance among human pathogens is widely regarded as one of the most serious threats to global health in the coming decades. Antimicrobial resistance is already thought to be responsible for tens of thousands of deaths in Europe each year.
Bombarded by Microbes
The study of the emergence and spread of genes that help these pathogens resist antibiotics has traditionally been limited to samples taken from infected people. However, the vast majority of microbes found in the human body are not pathogenic.
The human microbiome is a complex and dynamic community of millions of microbe species that live primarily in the gut and coexist with us. Microbiomes play an important role in health and disease, with the gut microbiome known to aid in food digestion and immune system development.
“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,”
said Professor Chris Quince, author of the research.
Profiling Gut Microbiome Genes
Researchers at the Earlham Institute and Quadram Institute in Norwich and collaborators in the Republic of Korea analyzed over 3,000 gut microbiome samples collected from healthy individuals in 14 countries to better understand the impact of antimicrobials on the gut microbiome.
They then compared the resistance genes identified in samples to those found in large genome collections in order to understand the movement of antimicrobial resistance 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. We needed to see the gene profile in the gut microbiome without the influence of any antimicrobials,”
explained Professor Quince.
They meticulously catalogued and recorded the number of antimicrobial resistance genes discovered in the samples by comparing the data to the Comprehensive Antibiotic Resistance Database, a public health resource that documents resistance genes.
National Antibiotic Consumption Rates
The average number of antimicrobial resistance genes per stool sample identified by the team was 16.
In addition, they discovered that the median number of genes varied among the 14 countries for which they collected data. For instance, they observed a fivefold difference in the median resistance levels between the Netherlands and Spain.
Using data from the World Health Organization and ResistanceMap, the team was able to demonstrate a strong correlation between the prevalence of antibiotic-resistant genes in a country and its antibiotic consumption rates.
“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.
Horizontal Gene Transfer
The fact that microbes are constantly sharing genes is why collateral damage is such a major issue. This process, known as horizontal gene transfer, aids in the spread of antimicrobial resistance genes between species.
Microbes and pathogen strains are constantly imported and exported by our bodies.
“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 Quince said.
It has been known for a number of years that antimicrobial resistance genes can spread extraordinarily rapidly among gut bacteria. This study is important because, for the first time, it can quantify the effect of national antibiotic use on our commensal bacteria and provide insight into the types of resistance we can expect to develop.
The researchers intend to conduct additional research and encourage others to do the same in order to investigate the relationship in additional nations and inform public health strategies.
The widespread usage of antimicrobials has driven the evolution of resistance in pathogenic microbes, both increased prevalence of antimicrobial resistance genes (ARGs) and their spread across species by horizontal gene transfer (HGT). However, the impact on the wider community of commensal microbes associated with the human body, the microbiome, is less well understood. Small-scale studies have determined the transient impacts of antibiotic consumption but we conduct an extensive survey of ARGs in 8972 metagenomes to determine the population-level impacts.
Focusing on 3096 gut microbiomes from healthy individuals not taking antibiotics we demonstrate highly significant correlations between both the total ARG abundance and diversity and per capita antibiotic usage rates across ten countries spanning three continents. Samples from China were notable outliers. We use a collection of 154,723 human-associated metagenome assembled genomes (MAGs) to link these ARGs to taxa and detect HGT. This reveals that the correlations in ARG abundance are driven by multi-species mobile ARGs shared between pathogens and commensals, within a highly connected central component of the network of MAGs and ARGs. We also observe that individual human gut ARG profiles cluster into two types or resistotypes. The less frequent resistotype has higher overall ARG abundance, is associated with certain classes of resistance, and is linked to species-specific genes in the Proteobacteria on the periphery of the ARG network.
- Kihyun Lee et al. Population-level impacts of antibiotic usage on the human gut microbiome. Nature Communications (2023). DOI: 10.1038/s41467-023-36633-7