The impact of long-term levofloxacin on the bacterial gut microbiome of young South African children

Disruptions to gut microbial communities in early life can have lasting effects on metabolism, immune function, and resistance to infections. Antibiotics, including levofloxacin, can alter gut microbiota composition, potentially leading to long-term dysbiosis. The long-term impact of levofloxacin on the gut microbiota, especially in young children, remains poorly understood. This study investigated the effects of prolonged levofloxacin therapy over 6 months on gut microbiota in children and the stability of these changes after treatment cessation. This work used samples that were collected as part of a cluster-randomized, double-blind, placebo-controlled trial that investigated the efficacy and safety of levofloxacin for multidrug-resistant (MDR) tuberculosis (TB) preventive treatment in healthy children under the age of five years exposed to MDR-TB in the home. Levofloxacin or placebo were administered daily for 24 weeks following randomization, and stool samples were taken at baseline, and at 24- and 48-week follow-up visits. Bacterial 16S rRNA sequencing was performed on the Illumina MiSeq platform and the changes in bacterial gut microbiota composition and diversity were assessed at different time points and compared between the levofloxacin and placebo arms for different age group. Changes in the functional potential of the gut microbiome were predicted based on the observed taxonomy. Gut microbiota analysis was stratified into three age groups: 0 to <1 year, 1 to <2 years, and 2 to <5 years. The richness and evenness of microbiota were not significantly reduced following 24 weeks of levofloxacin therapy in any group. However, in infants (<1 year), the expected natural microbial diversification was significantly stunted at the end of treatment and remained impaired 24 weeks after treatment completion (48-week visit). Differential abundance testing supported this finding, revealing that a greater number of taxa were negatively impacted in the levofloxacin-treated group. Despite these shifts, beta-diversity analysis indicated no significant differences in overall microbial composition between baseline and follow-up visits after antibiotic treatment. This study showed that the natural diversification of the gut microbiota is stunted in infants and does not recover even at 24 weeks following cessation of treatment. The gut microbiota of 2 to <5-year-old children demonstrated more resilience to the influence of antibiotics.