Co-localization of antibiotic resistance genes is widespread in the infant gut microbiome and associates with an immature gut microbial composition.

Publisher: BioMed Central Country of Publication: England NLM ID: 101615147 Publication Model: Electronic Cited Medium: Internet ISSN: 2049-2618 (Electronic) Linking ISSN: 20492618 NLM ISO Abbreviation: Microbiome Subsets: MEDLINE

Original Publication: London: BioMed Central, 2013-

Gastrointestinal Microbiome*/genetics ; Gastrointestinal Microbiome*/drug effects ; Anti-Bacterial Agents*/pharmacology ; Bacteria*/genetics ; Bacteria*/classification ; Bacteria*/drug effects ; Bacteria*/isolation & purification; Humans ; Infant ; Denmark ; Drug Resistance, Bacterial/genetics ; Genes, Bacterial/genetics ; Female ; Feces/microbiology ; Drug Resistance, Microbial/genetics ; Male ; Cohort Studies ; Infant, Newborn

Background: In environmental bacteria, the selective advantage of antibiotic resistance genes (ARGs) can be increased through co-localization with genes such as other ARGs, biocide resistance genes, metal resistance genes, and virulence genes (VGs). The gut microbiome of infants has been shown to contain numerous ARGs, however, co-localization related to ARGs is unknown during early life despite frequent exposures to biocides and metals from an early age.
Results: We conducted a comprehensive analysis of genetic co-localization of resistance genes in a cohort of 662 Danish children and examined the association between such co-localization and environmental factors as well as gut microbial maturation. Our study showed that co-localization of ARGs with other resistance and virulence genes is common in the early gut microbiome and is associated with gut bacteria that are indicative of low maturity. Statistical models showed that co-localization occurred mainly in the phylum Proteobacteria independent of high ARG content and contig length. We evaluated the stochasticity of co-localization occurrence using enrichment scores. The most common forms of co-localization involved tetracycline and fluoroquinolone resistance genes, and, on plasmids, co-localization predominantly occurred in the form of class 1 integrons. Antibiotic use caused a short-term increase in mobile ARGs, while non-mobile ARGs showed no significant change. Finally, we found that a high abundance of VGs was associated with low gut microbial maturity and that VGs showed even higher potential for mobility than ARGs.
Conclusions: We found that the phenomenon of co-localization between ARGs and other resistance and VGs was prevalent in the gut at the beginning of life. It reveals the diversity that sustains antibiotic resistance and therefore indirectly emphasizes the need to apply caution in the use of antimicrobial agents in clinical practice, animal husbandry, and daily life to mitigate the escalation of resistance. Video Abstract.
(© 2024. The Author(s).)

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BIOCODEX INTERNATIONAL GRANT 2022 BIOCODEX INTERNATIONAL GRANT; NNF17OC0025014 The Novo Nordisk Foundation; NNF17OC0025014 The Novo Nordisk Foundation; NNF17OC0025014 The Novo Nordisk Foundation; NNF17OC0025014 The Novo Nordisk Foundation; NNF17OC0025014 The Novo Nordisk Foundation; NNF17OC0025014 The Novo Nordisk Foundation; NNF17OC0025014 The Novo Nordisk Foundation; NNF17OC0025014 The Novo Nordisk Foundation; NNF17OC0025014 The Novo Nordisk Foundation

Keywords: Antibiotics resistance genes; Co-localization; Gut microbiome; Infants; Metagenomics

0 (Anti-Bacterial Agents)

Date Created: 20240510 Date Completed: 20240510 Latest Revision: 20240513

20240513

PMC11084089

10.1186/s40168-024-01800-5

38730321