PLoS Medicine (Jun 2023)
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. Vanessa C Harris and colleagues review the currently available literature to report how antibiotic use in children from low- and middle-income countries impacts the gut microbiome and, the implications for antimicrobial resistant infections. Author summary Why was this study done? Antibiotics can disturb the bacteria in the gut and drive the development of antimicrobial resistance (AMR). Children in low- and middle-income (LMIC) settings often receive (inappropriate) antibiotics and are at risk of antimicrobial-resistant infections that are harder and costlier to treat. Currently, little knowledge exists regarding the risks of antibiotic use in children in LMIC and the impact of antibiotics on the bacteria in their gut. In this review, we aimed to identify studies evaluating the impact of antibiotics in children in LMIC to better describe these unintended antibiotic side effects. What did the researchers do and find? We systematically collected studies performed in LMIC in children that reported the effects of antibiotics on gut bacteria and profiled their antibiotic resistance genes. Our search revealed a paucity of published studies focusing on this topic and we identified only a handful of eligible studies to include in the review. We compared these studies based on the antibiotic used and differential impacts on gut bacteria, i.e., gut microbiome profiles and/or resistance genes. We observed that among children in LMIC, antibiotics generally reduced the numbers of bacterial taxa in the gut and increased the number of bacterial taxa with AMR. What do these findings mean? Our study shows that antibiotic use alters the microbiome composition in the gut and may adversely impact the health of children in LMIC, e.g., by placing them at risk of antimicrobial-resistant infections. More research is needed to understand how different antibiotics alter the gut microbiome and resistome of children in LMIC. Antibiotic usage in these populations should be better regulated, in order to prevent these indirect impacts of antibiotic use and reduce the risk of antimicrobial-resistant infections.