bioRxiv Science⌕ Search
Home/Archive/bioRxiv

bioRxiv · 10.64898/2026.02.04.703743

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

Nel Van Zyl, K.·Whitelaw, A. C.·Hesseling, A. C.·Seddon, J. A.·Demers, A.-M.·Newton-Foot, M.
View original source ↗Export metadata ↓

Abstract

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.

Explore related subjects

microbiologyPreprint

Keep this discovery

Explore connections, maps & timelines

BibTeXRIS

Nel Van Zyl, K., Whitelaw, A. C., Hesseling, A. C., Seddon, J. A., Demers, A.-M., Newton-Foot, M.. 2026-02-04. The impact of long-term levofloxacin on the bacterial gut microbiome of young South African children. https://doi.org/10.64898/2026.02.04.703743

Cite the original work for its findings. Save a collection to share your selection of sources.

KEEP EXPLORING

Related preprints

bioRxiv2026

A population-scale landscape of the subgingival microbiome reveals divergent routes to periodontal dysbiosis

Periodontitis is an archetypical mucosal inflammatory disease in which microbiome dysbiosis at the tooth-epithelial interface interacts with host genetic and behavioral risk factors to drive immune-mediated tissue destruction. Although subgingival microbiome compositional shifts are thought to parallel disease severity, microbiome variation at the population-level and its relationship to periodontal clinical phenotypes and disease-modifying factors remain poorly defined. Here, we use unsupervised manifold learning to map the compositional landscape of the subgingival microbiome in 1,355 adults spanning periodontal health to severe periodontitis. We identified eight latent microbiome states organized along a branching continuum from eubiosis to dysbiosis. An intermediate microbial configuration marked ecological destabilization and bifurcation into two distinct periodontitis-associated dysbiotic trajectories, distinguished by links to gingival inflammation and smoking. Although the microbiome trajectories broadly tracked periodontal destruction, a minority of individuals showed discordant microbiome-clinical phenotypes, with some individuals with periodontitis retaining otherwise eubiotic microbiomes enriched for low-abundance pathobionts, while some cases of health or mild disease had highly dysbiotic communities, suggesting distinct host susceptibility. Together, these findings define a population-scale ecological landscape of the subgingival microbiome, reveal divergent trajectories to periodontal dysbiosis, and highlight heterogeneity in the relationship between microbial community structure and clinical disease expression.

microbiology↗
bioRxiv2026

The iron-binding siderophore enterobactin is required for the response of multi-drug resistant Klebsiella pneumoniae to zinc limitation

To persist during infection Klebsiella pneumoniae must overcome nutrient iron and zinc limitation imposed by the host immune system through a process called nutritional immunity. Secreted small molecule siderophores are a major virulence determinant of Klebsiella pneumoniae pathogenesis and are presumed to overcome nutritional immunity by binding iron for bacterial acquisition. In this work, we set out to identify how a multi-drug resistant K. pneumoniae grows in zinc limited environments. Using unbiased transcriptomics, proteomics, and an arrayed transposon screen, we identified that synthesis and uptake of the siderophore enterobactin is required to allow for growth in low zinc conditions. Iron-specific chelators did not replicate this phenotype and addition of supplemental iron through heme in growth media could not complement severe growth defects of enterobactin mutant K. pneumoniae experiencing zinc limitation. Finally, zinc starvation induced enterobactin production independent of the canonical zinc uptake regulator (Zur) transcription factor suggesting an unidentified regulatory mechanism by which Gram-negative pathogens may respond to zinc stress. Together, these studies expand the role of enterobactin beyond iron regulation and highlight a previously unreported link between iron and zinc homeostasis in Klebsiella pneumoniae.

microbiology↗
bioRxiv2026

A microbiota-derived protease links phage susceptibility to host epithelial responses

Bacteriophages are major ecological drivers of gut microbial ecology, yet whether bacterial mechanisms that determine phage susceptibility have consequences for the mammalian host remains poorly understood. Here, we identify dipeptidyl peptidase 11 (Dpp11a), the predominant active serine protease of the prevalent gut commensal Phocaeicola vulgatus, as an unexpected bacterial defence factor. Dpp11a protects against environmental proteases and confers resistance to bacteriophage infection. Metatranscriptomic analyses further reveal increased expression of both dpp11a and P. vulgatus-associated phage transcripts in ulcerative colitis stool samples, indicating that both components of this interaction are transcriptionally active in disease-associated human microbiomes. Using the microfluidic gut-on-a-chip co-culture model HuMiX, we show that the absence of Dpp11 is accompanied by altered epithelial tight-junction remodelling during phage-bacterial infection. Together, our findings reveal that the consequences of bacterial phage defence can extend beyond phage-bacterium interactions to the mammalian epithelium.

microbiology↗