Abstract
Background Low- and middle-income countries (LMICs) bear the largest mortality burden due to antimicrobial-resistant infections. Small-scale animal production and free-roaming domestic animals are common in many LMICs, yet data on zoonotic exchange of gut bacteria and antimicrobial resistance genes (ARGs) in low-income communities are sparse. Differences between rural and urban communities in population density, antibiotic use, and cohabitation with animals likely influence the frequency of transmission of gut bacterial communities and ARGs between humans and animals. Here, we determined the similarity in gut microbiomes, using 16S rRNA gene amplicon sequencing, and resistomes, using long-read metagenomics, between humans, chickens, and goats in rural compared to urban Bangladesh.
Results Gut microbiomes were more similar between humans and chickens in rural (where cohabitation is more common) compared to urban areas, but there was no difference for humans and goats. Urbanicity did not impact the similarity of human and animal resistomes; however, ARG abundance was higher in urban animals compared to rural animals. We identified substantial overlap of ARG alleles in humans and animals in both settings. Humans and chickens had more overlapping ARG alleles than humans and goats. All fecal hosts carried ARGs on contigs classified as potentially pathogenic bacteria – including Escherichia coli, Campylobacter jejuni, Clostridiodes difficile, and Klebsiella pneumoniae.
Conclusions While the development of antimicrobial resistance in animal gut microbiomes and subsequent transmission to humans has been demonstrated in intensive farming environments and high-income countries, evidence of zoonotic exchange of antimicrobial resistance in LMIC communities is lacking. This research provides genomic evidence of overlap of antimicrobial resistance genes between humans and animals, especially in urban communities, and highlights chickens as important reservoirs of antimicrobial resistance. Chicken and human gut microbiomes were more similar in rural Bangladesh, where cohabitation is more common. Incorporation of long-read metagenomics enabled characterization of bacterial hosts of resistance genes, which has not been possible in previous culture-independent studies using only short-read sequencing. These findings highlight the importance of developing strategies for combatting antimicrobial resistance that account for chickens being reservoirs of ARGs in community environments, especially in urban areas.
Competing Interest Statement
The authors have declared no competing interest.
Clinical Trial
This was not a clinical trial.
Funding Statement
This work was supported, in part, by the Bill & Melinda Gates Foundation [OPPGD759] to the University of California Berkeley. Under the grant conditions of the Foundation, a Creative Commons Attribution 4.0 Generic License has already been assigned to the Author Accepted Manuscript version that might arise from this submission. Lab processing was funded by a Tufts Institute of the Environment Environmental Research Fellowship awarded to JS and AJP's start-up funds at Tufts University. This material is based upon work supported by the NSF Postdoctoral Research Fellowships in Biology Program under Grant No. 1906957. Any opinions, findings, and conclusions or recommendations expressed in this material are those of the author(s) and do not necessarily reflect the views of the National Science Foundation.
Author Declarations
I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained.
Yes
The details of the IRB/oversight body that provided approval or exemption for the research described are given below:
The studies were approved by the icddr,b Ethical Review Committee (PR-11063, PR-13004), Johns Hopkins University Institutional Review Board (IRB) (00004795), University of California, Berkeley Committee for the Protection of Human Subjects (2011-09-3652), and Stanford University IRB (25863).
All necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived.
Yes
I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance).
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I have followed all appropriate research reporting guidelines and uploaded the relevant EQUATOR Network research reporting checklist(s) and other pertinent material as supplementary files, if applicable.
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Footnotes
jennaswarthout{at}gmail.com
ericafuhrmeister{at}gmail.com
latifah{at}stanford.edu
aharris5{at}ncsu.edu
alveeju{at}gmail.com
egurley1{at}jhu.edu
dr.satter{at}icddrb.org
ali.boehm{at}gmail.com
amyjanel{at}gmail.com
Data Availability
Metagenomic sequence reads and 16S rRNA amplicon sequences are available in the sequence read archive (SRA) under accession numbers SRR13059261- SRR13059374. Human sequences were removed from all samples. Relevant analysis scripts are available in GitHub (https://github.com/jennaswa/arg_bd).
List of Abbreviations
- LMIC
- low- and middle-income country
- ARG
- antimicrobial resistance gene
- USDA
- United States Department of Agriculture
- PCR
- polymerase chain reaction
- ONT
- Oxford Nanopore Technologies
- ASV
- amplicon sequence variant
- NCBI
- National Center for Biotechnology Information
- CDC
- Centers for Disease Control and Prevention
- MLS
- macrolide, lincosamide, and streptogramin B
- ESBL
- extended-spectrum beta-lactamase
- BLI
- beta-lactamase inhibitor