The Gut Microbiome of Healthy Vietnamese Adults and Children Is a Major Reservoir for Resistance Genes Against Critical Antimicrobials

Abstract

Antimicrobials are a key group of therapeutic agents. Given the animal/human population density and high antimicrobial consumption rate in Southeast Asia, the region is a focal area for monitoring antimicrobial resistance (AMR). Hypothesizing that the gastrointestinal tract of healthy individuals in Vietnam is a major source of AMR genes that may be transferred to pathogens, we performed shotgun metagenomic sequencing on fecal samples from 42 healthy Vietnamese people (21 children and 21 adults). We compared their microbiome profiles by age group and determined the composition of AMR genes. An analysis of the taxonomic profiles in the gut microbiome showed a clear differentiation by age, with young children (age <2 years) exhibiting a unique structure in comparison to adults and older children. We identified a total of 132 unique AMR genes, with MLS class resistance genes (ermB and lnuC) and tetracycline resistance genes being the almost ubiquitous across the study population. Notably, samples from younger children were significantly associated with a greater number of AMR genes than other age groups, including key signature genes associated with AMR pathogens (e.g., blaCTX-M, mphA). Our data suggest that the gut microbiome of those living in Vietnam, particularly young children, is a substantial reservoir of AMR genes, which can be transferred to circulating enteric pathogens. Our data supports the generation of longitudinal cohort studies of those living in urban and rural areas of developing countries to understand the behavior of these AMR reservoirs and their role in generating MDR and XDR pathogens.

Social demographics determinants for resistome and microbiome variation of a multiethnic community in Southern Malaysia

“…Nevertheless, our results are more or less comparable with the reported 764 gene ARG subtypes from neighbouring Singapore, which also observed the dominance of tetracycline and aminoglycoside resistance genes in urban wastewater 15 . Regardless of the observed quantity, the high diversity of ARGs observed in our cohort is aligned with other studies indicating the endemicity of antibiotic resistance in Southeast Asia 14 , 45 . In particular, the high prevalence of resistance genes against aminoglycosides, cephalosporins, macrolides, and fluoroquinolones is a significant concern, considering their status as critically important antimicrobials for the treatment of infectious diseases 46 .…”

“…The high consumption frequency reported is aligned with a 2019 report suggesting the endemicity of antibiotic resistance in Southeast Asia 44 . Peering deeper into the region, Pereira-Dias et al (2021) 14 recently reported the gut resistome of 42 children and healthy adults from Vietnam, detecting 132 ARGs, which is much lower than the 1038 ARGs detected in this cohort. However, our study also utilized a much larger sample size ( n = 200 versus n = 42) and sequencing reads (mean ~26 million reads per subject versus 12 million reads).…”

“…However, our study also utilized a much larger sample size ( n = 200 versus n = 42) and sequencing reads (mean ~26 million reads per subject versus 12 million reads). Additionally, the distinct gene abundance also likely arose from the different reference databases utilized, where Pereira-Dias et al 14 used the SRST2 database compared to the CARD and ARDB database used by the ARGs-OPA pipeline in this study. Nevertheless, our results are more or less comparable with the reported 764 gene ARG subtypes from neighbouring Singapore, which also observed the dominance of tetracycline and aminoglycoside resistance genes in urban wastewater 15 .…”

“…Despite the high burden of antibiotic resistance in the region, comprehensive resistome profiling studies are severely lacking. Among the limited studies available, Pereira-Dias et al (2021) 14 discovered a wide array of antibiotic-resistance genes in a cohort of 42 healthy Vietnamese individuals. However, the study was limited in scale and lacked complementary environmental and lifestyle data, hampering its interpretation.…”

The antibiotic resistance reservoir of the lung microbiome expands with age in a population of critically ill patients

“…As with the gastrointestinal tract, the respiratory tract harbors diverse microbial communities acquired early during life [4][5][6] that are continually influenced over the lifespan by exposures to organisms from the environment and other humans, as well as to antimicrobials. The gut, respiratory tract, and other human anatomical microbiomes serve as reservoirs for ARGs, or antimicrobial resistomes, and act as potential sites of ARG acquisition and transmission 7 .…”