Post-antibiotic Ocular Surface Microbiome in Children: A Cluster-Randomized Trial.
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ABSTRACT:
SUBMITTER: Doan T
PROVIDER: S-EPMC7384962 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:PurposeCarboxymethylcellulose is an artificial tear ingredient known to decrease gut microbiome diversity when ingested. This study examines the effect of carboxymethylcellulose on ocular surface microbiome diversity and composition.MethodsHealthy adult participants without significant ophthalmic disease or concurrent carboxymethylcellulose artificial tear use were allocated randomly to take carboxymethylcellulose or control polyethylene glycol artificial tears for seven days. Conjunctival swabs were collected before and after artificial tear treatment. This trial is registered at clinicaltrials.gov (NCT05292755). Primary outcomes included abundance of bacterial taxa and microbiome diversity as measured by the Chao-1 richness estimate, Shannon's phylogenetic diversity index, and UniFrac analysis. Secondary outcomes included Ocular Surface Disease Index scores and artificial tear compliance.ResultsOf the 80 enrolled participants, 66 completed the trial. Neither intervention affected Chao-1 richness (analysis of variance [ANOVA], P = 0.231) or Shannon's diversity index (ANOVA, P = 0.224). Microbiome samples did not separate by time point (permutation multivariate analysis of variance [PERMANOVA], P = 0.223) or intervention group (PERMANOVA, P = 0.668). LEfSe taxonomic analysis revealed that carboxymethylcellulose depleted several taxa including Bacteroides and Lachnoclostridium, but enriched Enterobacteriaceae, Citrobacter, and Gordonia. Both interventions decreased OSDI scores (Wilcoxon signed rank test, P < 0.05), but there was no significant difference between interventions (Mann-Whitney U, P = 0.54).ConclusionsCarboxymethylcellulose artificial tears increased Actinobacteriota but decreased Bacteroides and Firmicutes bacteria. Carboxymethylcellulose artificial tears do not affect ocular surface microbiome diversity and are not significantly more effective than polyethylene glycol artificial tears for dry eye treatment.Translational relevanceThe 16S microbiome analysis has revealed small changes in the ocular surface microbiome associated with artificial tear use.
| S-EPMC10424155 | biostudies-literature
Project description:PurposeThere is growing evidence for a critical role of the microbiome in ocular health and disease. We performed a prospective, observational study to characterize the ocular surface microbiome (OSM) in four chronic ocular surface diseases (OSDs) and healthy controls.MethodsSterile swabs were used to collect samples from each eye of 39 patients (78 eyes). Sterile technique and multiple controls were used to assess contamination during DNA extraction, amplification and sequencing. Concurrent use of topical antibiotics, steroids, and bandage contact lenses (BCLs) was documented.ResultsDespite the low biomass of the ocular surface, 47/78 (60%) eyes sampled had positive sequencing reads. We observed that half of patients (8/17, 47%) had distinct microbiomes in each eye. Healthy controls had a Lactobacillus/Streptococcus mixture or significant Corynebacterium. Staphylococcus predominated in 4/7 (57%) patients with Stevens-Johnson Syndrome (SJS) in at least one eye, compared to 0/10 healthy controls. Interestingly, 8/11 (73%) eyes with SJS were using BCLs, including 4/5 (80%) eyes dominated by Staphylococcus. Lax eyelid syndrome (LES) and Dry Eye Disease (DED) patients had similar OSMs, with Corynebacterium being the most prevalent bacteria. Alpha diversity was higher in controls and ocular graft-vs-host (oGVHD) patients compared to the other OSDs.ConclusionsOnly 50% of the 39 patients had similar microbiomes in each eye. A majority of healthy eyes had a Lactobacillus/Streptococcus mix or Corynebacterium microbiome. Staphylococcus predominated in SJS, Lactobacillus in oGVHD, and Corynebacterium in DED and LES. There may be an association between different OSDs and the microbiome.
| S-EPMC7905829 | biostudies-literature
Project description:Unlike other microbiomes of the body, the composition of the ocular surface microbiome (OSM) in children has yet to be thoroughly explored. Our goal was to evaluate the OSM in young infants and compare its composition to older children using both culture dependent and independent methodologies to assess for differences with age. Prospective, observational, cross-sectional study of children <18 years of age at a university-based institution. The mucosal surfaces of both eyes, nose and throat were swabbed with a forensic-quality swab. Half of the swab was plated for culture and the other half underwent 16S sequencing. Culture results and microbiome diversity were analyzed. Fifty patients (mean age 37 months, range 1-168 months) were enrolled. Forty-seven eyes of 30 patients had positive cultures; four eyes grew >1 species. Culture positive patients were older (43 vs. 29 months, P = 0.19). Additionally, older children had greater diversity than children under 6 months of age by 16S sequencing (P = 0.05). Staphylococcus species were predominant by culture (35/52 isolates) and by 16S sequencing. The OSM was fairly similar to the nose microbiome, whereas the throat microbiome differed significantly and had a higher abundance of Streptococcaceae (P = 0.001). The OSM is predominantly composed of Staphylococcus species in children, as demonstrated by both culture dependent and culture independent methods. Older children were more likely to have growth on culture and have more a complex bacterial milieu with 16S sequencing. 16S sequencing provides more robust information regarding the composition of the microbiomes than culture dependent methods.
| S-EPMC6269136 | biostudies-other
Project description:PurposeTo perform a pilot study to characterize the effect of clinical parameters on the ocular surface microbiome (OSM) in children and adults using 16s ribosomal RNA sequencing.MethodsProspective, cross-sectional study using 16s sequencing to evaluate the OSM. Comparisons were made in bacterial composition by 1) age, 2) gender, 3) sampling location of the ocular and periocular surfaces, and 4) topical drop use. 16s sequencing was performed using Illumina MiSeq 250 and analyzed using Qiime.ResultsThirty patients (15 children [mean 3.7 years], 15 adults [mean 60.4 years]) were sampled. Both principal coordinate analysis and unifrac distance analysis showed significant differences in the composition between the pediatric and adult OSMs (both p=0.001). The eyelid margin microbiota did not show any distinct clustering compared to conjunctiva within the pediatric samples but tended to show a distinction between anatomic sites in adult samples. No differences in OSM were noted by topical drop use.Conclusion16s sequencing is a useful tool in evaluating the OSM in patients of all ages, showing a distinct difference between pediatric and adult microbiomes.
| S-EPMC6040630 | biostudies-literature
Project description:This cross-sectional, age- and gender-matched study included 20 eyes of non-diabetic subjects (non-DM group) and 60 eyes of type 2 diabetes mellitus (DM group). Subgroups of DM were classified by diabetic retinopathy (DR) staging into no DR (DM-no DR), non-proliferative DR (DM-NPDR), proliferative DR (DM-PDR), and by glycemic control (well-controlled DM; HbA1c < 7%, poorly controlled DM; HbA1c ≥ 7%). Conjunctival swabs were performed for ocular surface microbiome analysis using conventional culture and next-generation sequencing analysis (NGS). A higher culture-positive rate was found in DM (15%) than in non-DM group (5%) (p value = 0.437). Pathogenic organisms and antibiotic-resistant strains were detected in the DR groups (DM-NPDR and DM-PDR). The NGS analysis showed that potentially pathogenic bacteria such as Enterobacteriaceae, Neisseriaceae, Escherichia-Shigella, and Pseudomonas predominated in DM, especially in DR. There was dissimilarity in the ocular surface microbiome between DM and non-DM groups. The subgroup analysis showed that the DR group had significantly different microbial community from DM-no DR and non-DM groups (p value < 0.05). The microbial community in the poorly controlled DM was also significantly different from well-controlled DM and non-DM groups (p < 0.001). Using the NGS method, our study is the first to signify the importance of DR and glycemic control status, which affect the changes in the ocular surface microbiome.
| S-EPMC9747965 | biostudies-literature
Project description:The World Health Organization (WHO) recommends environmental improvements such as latrine construction in the integrated trachoma control strategy, SAFE. We report a cluster-randomized trial assessing the effect of intensive latrine promotion on emergence of infection with ocular Chlamydia trachomatis after mass treatment with antibiotics.Twenty-four communities in Goncha Seso Enesie woreda, Amhara Regional State, Ethiopia, were enumerated, and a random selection of 60 children aged 0- 9 years in each was monitored for clinical signs of trachoma and ocular chlamydial infection at baseline, 12 and 24 months. All community members were offered treatment with a single dose of oral azithromycin or topical tetracycline. After treatment, 12 subkebeles were randomized to receive intensive latrine promotion. Mean cluster ocular infection in the latrine and the non-latrine arms were reduced from 45.5% (95% CI 34.1-56.8%) and 43.0% (95% CI 31.1-54.8%) respectively at baseline to 14.6% (95% CI 7.4-21.8%) and 14.8% (95% CI 8.9-20.8%) respectively at 24 months (P=0.93). Clinical signs fell from 72.0% (95% CI 58.2-85.5%) and 61.3% (95% CI 44.0-78.5%) at baseline to 45.8% (36.0-55.6%) and 48.5% (34.0-62.9%) respectively at 24 months (P=0.69). At 24 months, estimated household latrine coverage and use were 80.8% and 61.7% respectively where there had been intensive latrine promotion and 30.0% and 25.0% respectively in the single treatment only arm. We were unable to detect a difference in the prevalence of ocular chlamydial infection in children due to latrine construction.
| S-EPMC3139980 | biostudies-literature
Project description:Ocular surface microbiome in dupilumab associated ocular surface disease
| PRJEB57775 | ENA
Project description:BackgroundMass distributions of oral azithromycin have long been used to eliminate trachoma, and they are now being proposed to reduce childhood mortality. The observed benefit appears to be augmented with each additional treatment, suggesting a possible community-level effect. Here, we assess whether 2 biannual mass treatments of preschool children affect the community's gut microbiome at 6 months after the last distribution.MethodsIn this cluster-randomized controlled trial, children aged 1-60 months in the Dossa region of Niger were randomized at the village level to receive a single dose of azithromycin or placebo every 6 months. Fecal samples were collected 6 months after the second treatment for metagenomic deep sequencing. The prespecified primary outcome was the Euclidean PERMANOVA of the gut microbiome, or effectively the distance between the genus-level centroid at the community level, with the secondary outcome being the Simpson's α diversity.ResultsIn the azithromycin arm, the gut microbial structures were significantly different than in the placebo arm (Euclidean PERMANOVA, P < .001). Further, the diversity of the gut microbiome in the azithromycin arm was significantly lower than in the placebo arm (inverse Simpson's index, P = .005).ConclusionsTwo mass azithromycin administrations, 6 months apart, in preschool children led to long-term alterations of the gut microbiome structure and community diversity. Here, long-term microbial alterations in the community did not imply disease but were associated with an improvement in childhood mortality.Clinical trials registrationNCT02048007.
| S-EPMC6101535 | biostudies-literature
Project description:BackgroundMass drug administration (MDA) with azithromycin is the primary strategy for global trachoma control efforts. Numerous studies have reported secondary effects of MDA with azithromycin, including reductions in childhood mortality, diarrhoeal disease and malaria. Most recently, the MORDOR clinical trial demonstrated that MDA led to an overall reduction in all-cause childhood mortality in targeted communities. There is however concern about the potential of increased antimicrobial resistance in treated communities. This study evaluated the impact of azithromycin MDA on the prevalence of gastrointestinal carriage of macrolide-resistant bacteria in communities within the MORDOR Malawi study, additionally profiling changes in the gut microbiome after treatment. For faecal metagenomics, 60 children were sampled prior to treatment and 122 children after four rounds of MDA, half receiving azithromycin and half placebo.ResultsThe proportion of bacteria carrying macrolide resistance increased after azithromycin treatment. Diversity and global community structure of the gut was minimally impacted by treatment, however abundance of several species was altered by treatment. Notably, the putative human enteropathogen Escherichia albertii was more abundant after treatment.ConclusionsMDA with azithromycin increased carriage of macrolide-resistant bacteria, but had limited impact on clinically relevant bacteria. However, increased abundance of enteropathogenic Escherichia species after treatment requires further, higher resolution investigation. Future studies should focus on the number of treatments and administration schedule to ensure clinical benefits continue to outweigh costs in antimicrobial resistance carriage. Trial registration ClinicalTrial.gov, NCT02047981. Registered January 29th 2014, https://clinicaltrials.gov/ct2/show/NCT02047981.
| S-EPMC8740015 | biostudies-literature
Project description:PurposeThe aim of this study was to evaluate the effect of the 4 times per year mass azithromycin distributions on the ocular surface microbiome of children in a trachoma endemic area.MethodsIn this cluster-randomized controlled trial, children aged 1 to 10 years in rural communities in the Goncha Seso Enesie district of Ethiopia were randomized to either no treatment or treatment with a single dose of oral azithromycin (height-based dosing to approximate 20 mg/kg) every 3 months for 1 year. Post hoc analysis of ocular surface Chlamydia trachomatis load, microbial community diversity, and macrolide resistance determinants was performed to evaluate differences between treatment arms.ResultsOne thousand two hundred fifty-five children from 24 communities were included in the study. The mean azithromycin coverage in the treated communities was 80% (95% CI: 73%-86%). The average age was 5 years (95% CI: 4-5). Ocular surface C. trachomatis load was reduced in children treated with the 4 times per year azithromycin ( P = 0.0003). Neisseria gonorrhoeae , Neisseria lactamica , and Neisseria meningitidis were more abundant in the no-treatment arm compared with the treated arm. The macrolide resistance gene ermB was not different between arms ( P = 0.63), but mefA / E was increased ( P = 0.04) in the azithromycin-treated arm.ConclusionsWe found a reduction in the load of C. trachomatis and 3 Neisseria species in communities treated with azithromycin. These benefits came at the cost of selection for macrolide resistance.
| S-EPMC8894504 | biostudies-literature