Commensal microflora in human conjunctiva; characteristics of microflora in the patients with chronic ocular graft-versus-host disease

Shimizu, Eisuke; Ogawa, Yoko; Saijo, Yumiko; Yamane, Mio; Uchino, Makoto; Kamoi, Mizuka; Fukui, Masaki; Yang, Fan; He, Jingliang; Mukai, Sonoyo; Ohta, Michio

doi:10.1016/j.jtos.2019.02.001

Cited by 53 publications

(38 citation statements)

References 38 publications

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“…Our findings demonstrated the alteration of ocular microbiome in term of diversity and higher proportion of potentially pathogenic microorganism. These changes may be related to severe ocular surface abnormalities including epithelial damage, reduction of aqueous and mucin layer, etc., as reported by Shimizu, et al 23 . The dysfunction may impair the ability to eliminate pathogens from ocular surface and affect microbial community.…”

Section: Scientific Reports |supporting

confidence: 71%

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Comparison of the ocular microbiome between chronic Stevens-Johnson syndrome patients and healthy subjects

Kittipibul

Puangsricharern

Chatsuwan

2020

Sci Rep

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Stevens -Johnson syndrome (SJS) has manifestation through the exfoliation of epidermis and mucosaltissue. Ocular surface is usually affected in acute and chronic stage. The patients are usually suffered from chronic ocular sequelae including symblepharon, limbal stem cell deficiency, etc. Furthermore, ocular microbiome may also be altered in SJS. This is prospective, age and sex matched analytical study which including 20 chronic SJS patients and 20 healthy subjects for specimen collection from inferior conjunctiva for microbiome analysis by conventional cultures and next-Generation Sequencing (nGS) methods. Significant higher proportion of positive-cultured specimen was demonstrated in SJS group (SJS group 60%, healthy 10%, p-value = 0.001). In addition, NGS which providing high-throughput sequencing has demonstrated the greater diversity of microbial species. the higher proportion of pathogenic microorganisms including Pseudomonas spp., Staphylococcus spp., Streptococcus spp., Acinetobacter spp. was shown in SJS group. ocular surface in SJS is usually occupied by more diverse microorganisms with increased proportion of pathogenic species. This condition may affect chronic inflammation and opportunistic infections in SJS group. In order to prevent and treat infection in these patients, appropriate antibiotics based on bacterial examination should be considered as the first-line treatment in the SJS patients.Stevens -Johnson syndrome (SJS) is an abnormal immune-mediated responses stimulated by medications such as sulfonamides, allopurinol, cold medicines including paracetamol 1 and systemic infections caused by virus and mycoplasma. Incidence of SJS is 1.2-6 out of 1,000,000 persons per year 2 . Although the incidence of diseases is low, the mortality rate is high ranging from 1% to 5% 2 . Patients usually present with severe, acute blistering disorders that affect the skin and mucous membranes involving oral mucosa and ocular surface 3 . Ocular involvement has been reported in 25-75% of SJS patients 2 . In the acute phase, patients usually develop conjunctivitis, corneal abrasion, and pseudo-membrane formation. While chronic ocular sequelae develop in 35% of cases, including eyelid irregularity, symblepharon formation, limbal stem cell deficiency (LSCD), and keratinization, leading to poor vision 2 .Recent interests are focused in the change of ocular microbiomes in this devastating disease. Several studies reported alteration of the ocular microbiomes in SJS patients, compared to healthy subjects. In healthy eyes, the most common microorganisms are Staphylococcus coagulase negative, Corynebacterium, and Propionibacterium 4,5 which are mainly gram-positive bacteria colonized in the ocular surface. In SJS, more pathogenic species are found including gram-negative bacteria. Frizon, et al. reported different compositions of microorganisms in SJS patients consisting of 55% of gram-positive cocci, 19% of gram-positive bacilli, and 25% of gram-negative bacilli 4 . They also found that these pathogenic organisms showed...

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Section: Scientific Reports |supporting

confidence: 71%

“…Proteobacteria). The more extensive species in NGS analysis may indicate the better performance to detect small amounts of microbes, slow-growing and non-cultivable microbial species 23 .…”

Section: Scientific Reports |mentioning

confidence: 99%

Comparison of the ocular microbiome between chronic Stevens-Johnson syndrome patients and healthy subjects

Kittipibul

Puangsricharern

Chatsuwan

2020

Sci Rep

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“…31 Interesting, alpha-hemolytic Streptococcus (which includes S. pneumoniae and S. sanguinis ) and H. Influenzae were observed on the ocular surface of oGVHD patients using culture-based methods. 32 These results indicate that the composition of conjunctival microbiota is associated with specific types of AC, which potentially provides novel aspects for the prevention and treatment of ocular allergy.…”

Section: Distinct Microbial Signatures Of Sac/pac and Vkcmentioning

confidence: 81%

Characterization of conjunctival microbiome dysbiosis associated with allergic conjunctivitis

Liang

Zhang

et al. 2020

Preprint

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Background: Evidence shows that the microbiome plays an important role in allergic diseases. The associations between the conjunctival microbiome dysbiosis and ocular allergy remain unknown. This study investigates the characteristics of the conjunctival microbiome in allergic conjunctivitis (AC). Methods: We performed metagenomic shotgun sequencing on conjunctival samples from 48 healthy subjects and 39 patients with AC. The AC group comprised 21 patients with seasonal allergic conjunctivitis or perennial allergic conjunctivitis (SAC/PAC) and 18 patients with vernal keratoconjunctivitis (VKC). Results: We identified a signature microbiome associated with the dysbiosis of conjunctival microbiota on the ocular surface of patients with AC. Interestingly, SAC/PAC and VKC harbor distinct microbial communities. Specifically, Brevibacterium aurantiacum is enriched in SAC/PAC, whereas a group of Streptococcus species and Haemophilus parainfluenzae are enriched in VKC. Conclusion: Dysbiosis of conjunctival microbiome is found on the ocular surface of AC patients. These results suggest a new microbial mechanism of AC and provide a potential target for AC treatment.

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“…Pathogenic bacteria such as a-hemolitic Streptococcus, Haemophilus influenza, and Enterobacter cloacae were also detected more frequently in patients suffering from ocular cGvHD. These results suggest that alternations of microbes may be involved in the pathogenic process of ocular cGvHD (121). A potential explanation for the broader bacterial diversity in ocular cGvHD may be the loss of protective factors, including secretory immunoglobulin A (SIgA) and defensins, as well as alteration of the quantity of tear fluid.…”

Section: Microbiome and Cgvhdmentioning

confidence: 96%

“…Shimizu et al ( 121 ) explored the status of microbes in the ocular surface in patients with ocular cGvHD and discovered alterations in the composition of ocular surface microbes. Approximately fifty percent of alloHSCT recipients developed dry eye syndrome, the main phenotype of ocular cGvHD within 2 years after alloHSCT.…”

Section: Microbiome and Cgvhdmentioning

confidence: 99%

Potential Novel Biomarkers in Chronic Graft-Versus-Host Disease

et al. 2020

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Prognostic, diagnostic or predictive biomarkers are urgently needed for assessment of chronic graft-versus-host disease (cGvHD), a major risk for patients undergoing allogeneic hematopoietic stem cell transplantation. The main goal of this review generated within the COST Action EUROGRAFT “Integrated European Network on Chronic Graft Versus Host Disease” was to identify potential novel biomarkers for cGvHD besides the widely accepted molecular and cellular biomarkers. Thus, the focus was on cellular biomarkers, alloantibodies, glycomics, endothelial derived particles, extracellular vesicles, microbiome, epigenetic and neurologic changes in cGvHD patients. Both host-reactive antibodies in general, and particularly alloantibodies have been associated with cGvHD and require further consideration. Glycans attached to IgG modulate its activity and represent a promising predictive and/or stratification biomarker for cGVHD. Furthermore, epigenetic changes such as microRNAs and DNA methylation represent potential biomarkers for monitoring cGvHD patients and novel targets for developing new treatment approaches. Finally, the microbiome likely affects the pathophysiology of cGvHD; bacterial strains as well as microbial metabolites could display potential biomarkers for dysbiosis and risk for the development of cGvHD. In summary, although there are no validated biomarkers currently available for clinical use to better inform on the diagnosis, prognosis or prediction of outcome for cGvHD, many novel sources of potential markers have shown promise and warrant further investigation using well characterized, multi-center patient cohorts.

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Commensal microflora in human conjunctiva; characteristics of microflora in the patients with chronic ocular graft-versus-host disease

Cited by 53 publications

References 38 publications

Comparison of the ocular microbiome between chronic Stevens-Johnson syndrome patients and healthy subjects

Comparison of the ocular microbiome between chronic Stevens-Johnson syndrome patients and healthy subjects

Characterization of conjunctival microbiome dysbiosis associated with allergic conjunctivitis

Potential Novel Biomarkers in Chronic Graft-Versus-Host Disease

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