Six months of levofloxacin stalls infant gut microbiome growth

Early life is a critical window when the gut microbiome develops and helps shape metabolism, immune function and resistance to infections. Antibiotics given during this period can change which bacteria live in the gut and how those communities form, with possible long-term consequences. To understand these effects, Kristien Nel Van Zyl and colleagues used samples from a cluster-randomized, double-blind, placebo-controlled trial that tested levofloxacin for multidrug-resistant (MDR) tuberculosis (TB) preventive treatment. The trial enrolled healthy children under five years of age who had been exposed to MDR-TB in the home. Participants were randomly assigned to receive daily levofloxacin or placebo for 24 weeks. Stool samples were collected at the start of the study (baseline), at the end of the 24-week treatment period, and again at a 48-week visit, 24 weeks after stopping study drug. The research team then examined how prolonged levofloxacin affected the developing gut bacterial communities and whether any changes persisted after treatment ended. By focusing on young South African children across a range of ages, the study aimed to capture how antibiotic exposure interacts with the natural stages of microbiome development.

To measure bacterial changes, the investigators performed bacterial 16S rRNA sequencing on the Illumina MiSeq platform and compared gut microbiota composition and diversity across time points and treatment arms. Analysis was stratified into three age groups: 0 to <1 year, 1 to <2 years, and 2 to <5 years. The team assessed richness (how many different bacteria are present) and evenness (how balanced they are) as well as overall community differences. After 24 weeks of levofloxacin therapy, richness and evenness were not significantly reduced in any age group when compared directly to placebo. However, infants under 1 year showed a clear departure from expected development: the normal increase in microbial diversity that occurs in early life was significantly stunted at the end of treatment and remained impaired at the 48-week visit, 24 weeks after treatment stopped. Differential abundance testing supported this pattern, showing a greater number of taxa negatively impacted in the levofloxacin-treated group. Despite these shifts in specific taxa and developmental patterns, beta-diversity analysis did not find significant differences in overall microbial composition between baseline and follow-up visits. Children aged 2 to <5 years showed more resilience to the influence of antibiotics.

The findings indicate that prolonged use of levofloxacin during infancy can interfere with the natural maturation of the gut microbiome and that these effects may persist for at least six months after starting treatment and for 24 weeks after stopping. For infants, the expected diversification of gut bacterial communities was blunted and did not recover within the study follow-up period, while older preschool children appeared more able to withstand the antibiotic’s impact. This matters because early microbiome development contributes to long-term health, so altering that trajectory could have consequences beyond the immediate goal of preventing MDR-TB. The results do not show wholesale collapse of the microbiome—overall richness and evenness were not significantly reduced and beta-diversity measures were similar—but they do highlight age-dependent sensitivity to antibiotic exposure. These patterns should inform clinicians and public health decision-makers weighing the benefits of levofloxacin for MDR-TB prevention against potential developmental effects on the gut microbiome, and they point to the importance of monitoring and considering age when prescribing prolonged antibiotic preventive therapy.