Impact of antibiotics on gut microbiome composition and resistome in the first years of life in low- to middle-income countries: A systematic review

Abstract

Background Inappropriate antimicrobial usage is a key driver of antimicrobial resistance (AMR). Low- and middle-income countries (LMICs) are disproportionately burdened by AMR and young children are especially vulnerable to infections with AMR-bearing pathogens. The impact of antibiotics on the microbiome, selection, persistence, and horizontal spread of AMR genes is insufficiently characterized and understood in children in LMICs. This systematic review aims to collate and evaluate the available literature describing the impact of antibiotics on the infant gut microbiome and resistome in LMICs. Methods and findings In this systematic review, we searched the online databases MEDLINE (1946 to 28 January 2023), EMBASE (1947 to 28 January 2023), SCOPUS (1945 to 29 January 2023), WHO Global Index Medicus (searched up to 29 January 2023), and SciELO (searched up to 29 January 2023). A total of 4,369 articles were retrieved across the databases. Duplicates were removed resulting in 2,748 unique articles. Screening by title and abstract excluded 2,666 articles, 92 articles were assessed based on the full text, and 10 studies met the eligibility criteria that included human studies conducted in LMICs among children below the age of 2 that reported gut microbiome composition and/or resistome composition (AMR genes) following antibiotic usage. The included studies were all randomized control trials (RCTs) and were assessed for risk of bias using the Cochrane risk-of-bias for randomized studies tool. Overall, antibiotics reduced gut microbiome diversity and increased antibiotic-specific resistance gene abundance in antibiotic treatment groups as compared to the placebo. The most widely tested antibiotic was azithromycin that decreased the diversity of the gut microbiome and significantly increased macrolide resistance as early as 5 days posttreatment. A major limitation of this study was paucity of available studies that cover this subject area. Specifically, the range of antibiotics assessed did not include the most commonly used antibiotics in LMIC populations. Conclusion In this study, we observed that antibiotics significantly reduce the diversity and alter the composition of the infant gut microbiome in LMICs, while concomitantly selecting for resistance genes whose persistence can last for months following treatment. Considerable heterogeneity in study methodology, timing and duration of sampling, and sequencing methodology in currently available research limit insights into antibiotic impacts on the microbiome and resistome in children in LMICs. More research is urgently needed to fill this gap in order to better understand whether antibiotic-driven reductions in microbiome diversity and selection of AMR genes place LMIC children at risk for adverse health outcomes, including infections with AMR-bearing pathogens.

Sugar types, genetic predictors of the gut microbiome, and the risk of chronic kidney disease: a prospective cohort study

“…Considering the dynamic nature of the gut microbiome and the fact that host genetics alone do not exclusively determine its diversity, we additionally adjusted for external gut microbiota-associated factors including healthy dietary components (intake of fiber, vegetables, fruit, whole grains, and poultry; g day −1 ), [35][36][37] geographic location (England area or non-England area), 38 and antibiotic usage as a child or a teenager (yes, no). 39 Stratification and interaction analyses were also conducted for the PGS of the eGFR to evaluate the modification effect of the genetically predicted eGFR.…”

Microbiome Dynamics: A Paradigm Shift in Combatting Infectious Diseases

“…Additionally, antibiotics can have broad impacts on the microbiome, targeting not only the causative agent but also commensal organisms. Antibiotics disrupt the healthy balance of gut flora, leading to a reduction in diversity and changes in both populations and functions [72,73]. This disruption can also contribute to the spread of antibiotic resistance.…”

Influence of age, socioeconomic status, and location on the infant gut resistome across populations

“…The number of studies reporting the presence and source of antibiotic resistance genes (ARGs) in infants has increased drastically owing to the dire situation created by the increasing spread, abundance, ubiquitous nature of ARGs and the high abundance of ARGs reported in Low – to Middle – income countries. 16 , 17 Recent studies have shed light on ARG abundance and the extent to which several factors affect it. 16 , 18–20 Studies have demonstrated a high abundance of ARGs in infants, even in the absence of antibiotic exposure, making the infant gut a reservoir of ARGs.…”