Abstract
Livestock farming consumes more than 70% of global antibiotics annually, making livestock manures an important vector of anthropogenically influenced antibiotic resistance genes (ARGs). The global pattern of the livestock resistome, its driving mechanisms, and transmission potential to the clinic are not well assessed. We analyzed 4017 livestock manure metagenomes from 26 countries and constructed a comprehensive catalog of livestock ARGs and metagenome-assembled genomes. Livestock resistome is a substantial reservoir of known (2291 subtypes) and latent ARGs (3166 subtypes) and is highly connectable to human resistomes. We depicted the global pattern of livestock resistome and prevalence of clinically critical ARGs, highlighting the role of farm and human antibiotic stewardship in shaping livestock resistome. We developed a risk-assessment framework by integrating mobility potential, clinical significance, and host pathogenic relevance, and prioritized higher risk livestock ARGs, producing a predictive global map of livestock resistome risks that can help guide research and policy.
Generated Summary
This research article presents a comprehensive analysis of livestock resistomes, focusing on the global patterns of antibiotic resistance genes (ARGs) in livestock manures. The study analyzed 4017 livestock manure metagenomes from 26 countries, constructing a detailed catalog of livestock ARGs and metagenome-assembled genomes. The research employs a risk-assessment framework to prioritize ARGs based on their mobility potential, clinical significance, and host pathogenic relevance, leading to the development of a predictive global map of livestock resistome risks. The methodology involves metagenomic analysis, ARG identification, and risk assessment, integrating factors such as ARG abundance, host range, and clinical importance. Statistical analyses, including PCoA and SVR modeling, are used to understand the distribution and risks associated with livestock resistomes. The aim is to provide insights for monitoring antibiotic resistance in livestock farming and to inform policy for curbing the spread of antibiotic resistance.
Key Findings & Statistics
- The study analyzed 4017 livestock manure metagenomes from 26 countries.
- The research identified 2291 ARG subtypes in the livestock manure metagenomes.
- A total of 3166 latent ARGs were predicted in livestock manures.
- Chicken manure had the highest ARG diversity (2107 subtypes), followed by swine (1779 subtypes) and bovine manures (1546 subtypes).
- On average, each chicken manure sample carried 246 ARG subtypes.
- 38 ARGs were detected in more than 90% of livestock manure samples.
- 123,872 metagenome-assembled genomes (MAGs) were constructed from livestock manure metagenomes.
- 563 ARGs were identified from ARG-carrying hosts.
- Approximately 34% of ARG-carrying MAGs contained genes coding for resistance to at least three antibiotic classes.
- The average resistome abundance in chicken and swine metagenomes was 2.0 times of that in human feces, 2.5 times of that in sewage, and 18.3 times of that in soil.
- Chicken and swine manure resistomes had the highest ARG abundance among all ARG reservoirs.
- Livestock manures harbored the highest ARG diversity except for sewage.
- The research identified 44 high-risk ARGs (R1 level).
- Chicken manure exhibited the highest resistome risk (0.94 ± 1.41), followed by swine manure (0.39 ± 0.33), with bovine manure presenting the lowest risk (0.09 ± 0.11).
- The swine manure resistome diversity of Asia (246 ARGs) and abundance (3.93 copies per cell) was significantly higher than other continents (P < 0.01).
- The abundance of tetracylcine resistance genes in swine was much higher in Asia (3.93 copies per cell) than in any other continent.
- The prevalence of mcr was higher in Bulgaria and Denmark than in other countries.
- The resistome abundance in bovine manure in China was 15.2% of that in Canada.
Other Important Findings
- The study revealed that livestock manures serve as a significant reservoir for ARGs, with a high degree of connectivity to human resistomes.
- The research identified significant differences in resistome profiles among different animal hosts, highlighting the impact of host-specific factors.
- The study prioritized ARGs based on risk, identifying 44 high-risk ARGs that pose a greater threat due to their potential to transfer to pathogens and impact antibiotic therapy.
- The study found that livestock manure resistomes are shaped by animal hosts, with chicken manure having the highest risk scores.
- The study developed predictive models to map the global distribution of livestock resistome risks.
- The findings highlight that the resistome risk in chicken and swine manures exhibited clear continental and national patterns.
Limitations Noted in the Document
- The study acknowledges limitations in the metagenomic data, such as the potential to miss low-abundance ARGs and the inability to provide absolute abundance measurements.
- The study notes that the risk assessment framework does not include all ARGs and that the host and mobility information relies on inferred data.
- The study’s framework is limited in determining phenotypic traits such as pathogenicity, which are strain and environment-dependent, and resistance phenotypes.
- The study highlights that a precise risk evaluation of an ARG requires strain-level clinical validation and experimental data, which goes beyond the scope of the current assessment framework.
Conclusion
The study underscores the significant role of livestock manures as reservoirs of antibiotic resistance genes, emphasizing the need for enhanced surveillance and targeted interventions. The identification of high-risk ARGs and the development of a risk assessment framework provide valuable tools for monitoring and managing antibiotic resistance in livestock settings. The global predictive map of resistome risks offers a crucial overview of the antibiotic resistance threat in livestock manure. The findings call for focused attention on resistome risks in major livestock-producing countries and highlight the impact of antibiotic usage, livestock practices, and economic factors on the spread of antibiotic resistance. The study’s conclusions advocate for the implementation of judicious farm management practices to mitigate antibiotic resistance in livestock farming. The study’s approach and methodology can be applied to risk prioritization of ARGs in other environmental contexts. The authors’ final thoughts emphasize the importance of understanding the spread of antibiotic resistance and propose livestock manure as an important sentinel environment. The high-risk ARGs (R1 level), representing those more likely to be transferred to lethal pathogens, underscore the urgency of addressing antibiotic resistance. The study results highlight the necessity for comprehensive measures to limit the transmission of ARGs, protect public health, and ensure the sustained effectiveness of antimicrobial therapy. The study’s emphasis on actionable insights underscores the need to formulate rational policies aimed at curbing the spread of antibiotic resistance.