Population-level impacts of antibiotic usage on the human gut microbiome

Abstract

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.

Exploring the effects of antimicrobial treatment on the gut and oral microbiomes and resistomes from elderly long-term care facility residents via shotgun DNA sequencing

“…Within-subject comparison of the total abundance of antimicrobial resistance genes between the samples before, during and 2–4 weeks after antimicrobial treatment. On the y -axis: per-sample summation of abundance levels, expressed as ‘copies per genome (cpg)’ [22] calculated for each ARG family, as in . Left: two individuals from whom the stool samples were collected before and during (6–8 days) antimicrobial treatment.…”

Antimicrobial Resistance in the Global Health Network: Known Unknowns and Challenges for Efficient Responses in the 21st Century

“…Although not included in any surveillance program, metagenomics-enabled surveillance methods offer the opportunity to improve the detection of both known and yet-to-emerge pathogens [161]. The analysis of the intestinal and respiratory microbiomes and the resistomes may also allow clarifying fundamen-tal questions, such as the host's susceptibility to infection, therapeutic regiments, fecal transplantation, long-term AMR colonization, or health response to antimicrobial disturbances [65,[162][163][164][165]. Other relevant and unexplored aspects are related to the microbiome of the hospital-built environment, an area of increasing interest in research agendas [166,167].…”

“…Counterfeit and substandard antibiotics represent up to one third of the available pharmaceuticals in LMICs (42% of all reports received by the WHO Global Surveillance and Monitoring System on substandard and falsified medicines worldwide came from Africa, most corresponding to antibiotics and antimalarials) [32,172]. Of special concern is the scope of hospital and outpatient drug stewardship programs because many non-antibiotic drugs have an antibiotic effect and can contribute to the selection of MDR (bystander selection) [163,173,174] (Figure 2).…”

Ultrasensitive Dual-Mode Visual/Photoelectrochemical Bioassay for Antibiotic Resistance Genes through Incorporating Rolling Circle Amplicons into a Tailored Nanoassembly

“…As emerging contaminants in the environment, antibiotic resistance genes (ARGs) have garnered extensive attention due to the ability of widespread through horizontal gene transfer and their environmental persistence, posing a severe threat to ecological safety and human health . Endowed with “easy-to-get, hard-to-lose” traits, ARGs are found in various environmental media, such as air, soil, and wastewater. − Moreover, different types of ARGs may frequently coexist in the same region, leading to the emergence of multidrug-resistant bacteria and causing a greater threat to human health .…”