Metagenomic Profiling of the Ocular Surface Microbiome in Patients After Allogeneic Hematopoietic Stem Cell Transplantation

Li, Jing; Liang, Qiaoxing; Huang, Fen; Liao, Yinglin; Zhao, Wenxin; Yang, Jing; Wen, Xiaofeng; Li, Xifang; Chen, Tingting; Guo, Shixin; Liang, Juanran; Wei, Lai; Liang, Lingyi

doi:10.1016/j.ajo.2022.04.026

Cited by 8 publications

(11 citation statements)

References 39 publications

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“…Data from the present study shows that OSM diversity indexes and relative abundances do not significantly change from pre- to post-HSCT as a whole. In our cohort, the main genera identified in post-HSCT patients are Staphylococcus , Corynbeacterium , Pseudomonas , Chryseobacterium , in agreement with those reported in the two previous studies on the same issue [ 27 , 28 ]. An attempt to better document and group different OSM compositions according to the correlation between pre- and post-HSCT highlighted four different profiles, but no significant correlation was found.…”

Section: Discussionsupporting

confidence: 92%

“…This aspect was specifically evaluated with regard to the gut microbiome, and still little is known on the influence eventually exerted by the OSM on oGVHD development. A few previous studies compared healthy subjects with post-HSCT patients who had or had not developed oGVHD, reporting inconsistent results in terms of OSM diversity indexes and composition [ 26 , 27 , 28 ]. The discrepancies in these studies’ results are possibly due to cross-sectional trial design matching heterogeneous populations and differences in methodology.…”

Section: Discussionmentioning

confidence: 99%

“…Shimizu et al found by conventional culture techniques that among 40 post-HSCT patients, GVHD patients showed more diversified microbial communities in their conjunctiva compared with the nonGVHD patients and the controls [ 26 ]. Two other studies characterised the OSM of post-allogenic HSCT patients with or without oGVHD through metagenomic shotgun sequencing and reached opposite results, as a decrease in the OSM diversity of post-HSCT patients compared to healthy controls was reported in both [ 27 , 28 ]. This could be due to the heterogeneous populations included in the studies and the use of different techniques, as the first study used traditional culture methods and the other two opted for next-generation sequencing methods.…”

Section: Introductionmentioning

confidence: 99%

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Longitudinal Changes of Ocular Surface Microbiome in Patients Undergoing Hemopoietic Stem Cell Transplant (HSCT)

Clougher,

Severgnini,

Marangoni

et al. 2023

JCM

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Purpose: To evaluate changes in the ocular surface microbiome (OSM) between pre- and post-haemopoietic stem cell transplant (HSCT) in the same patient, and to assess the potential impact of these changes in ocular graft-versus-host disease (o)GVHD development. Methods: Lower fornix conjunctival swabs of 24 patients were obtained before and after HSCT and subjected to DNA extraction for amplification and sequencing of the V3-V4 regions of the bacterial 16S rRNA gene. The obtained reads were reconstructed, filtered, and clustered into zero-radius operational taxonomic units (zOTUs) at 97% identity level before taxonomic assignment, and biodiversity indexes were calculated. Transplant characteristics were recorded, and dry eye was diagnosed and staged 1–4 according to the Dry Eye WorkShop (DEWS) score. Results: No significant difference in OSM alpha diversity between pre- and post-transplant was found. A significant difference in beta diversity was observed between patients with a DEWS score of 1 versus 3 (p = 0.035). Increased corneal damage between pre- and post-HSCT was significantly associated with a decrease in alpha diversity. The changes in OSM were not associated with oGVHD, nor with any transplant parameter. Conclusions: This preliminary study is the first study to analyse changes in the OSM before and after HSCT longitudinally. No trend in OSM biodiversity, microbial profile, or overall composition changes before and after HSCT was significant or associated with oGVHD onset. The great variability in the observed OSM profiles seems to suggest the absence of a patient-specific OSM “signature”.

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Section: Discussionsupporting

confidence: 92%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Longitudinal Changes of Ocular Surface Microbiome in Patients Undergoing Hemopoietic Stem Cell Transplant (HSCT)

Clougher,

Severgnini,

Marangoni

et al. 2023

JCM

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“…In addition, due to the decrease of goblet cells and the mucin layer and other factors, ocular surface microbes were showed more diverse in the ocular GVHD patients compared with non-ocular GVHD patients ( 78 ). However, A prospective study reported a different result in which the microbiome on the ocular surface was characterized by a loss of diversity in ocular GVHD patients ( 79 ). Both investigations indicated that the ocular surface microbial dysbiosis is involved in the underlying microbial mechanism of ocular GVHD, but further investigations are warranted to explore the concrete mechanisms and therapeutic targets ( 80 ).…”

Section: Pathogenic Mechanism and Novel Therapeutic Targetsmentioning

confidence: 99%

Recent advances in ocular graft-versus-host disease

Cheng

Huang

et al. 2023

Front. Immunol.

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Ocular graft-versus-host-disease (GVHD) remains a significant clinical complication after allogeneic hematopoietic stem cell transplantation. Impaired visual function, pain, and other symptoms severely affect affected individuals’ quality of life. However, the diagnosis of and therapy for ocular GVHD involve a multidisciplinary approach and remain challenging for both hematologists and ophthalmologists, as there are no unified international criteria. Through an exploration of the complex pathogenesis of ocular GVHD, this review comprehensively summarizes the pathogenic mechanism, related tear biomarkers, and clinical characteristics of this disease. Novel therapies based on the mechanisms are also discussed to provide insights into the ocular GVHD treatment.

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“…Pulmonary toxicities and changes in the pulmonary microbiome have also been found to be coassociated in pediatric alloHCT patients 33,34 . Changes in the ocular microbiota have also been observed in patients with ocular cGVHD, including in composition of bacteria as well as viruses 35 . Whether the microbiome of the oral cavity or upper gut could be similarly associated with upper GI aGVHD has not yet been well studied, although the dental biofilm microbiome has been reported to be associated with aGVHD 36 …”

Section: The Microbiome and Allohctmentioning

confidence: 99%

The Microbiome and Its Impact on Allogeneic Hematopoietic Cell Transplantation

Malard

Jenq

2023

Cancer J

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Allogeneic hematopoietic cell transplantation (alloHCT) is a standard curative therapy for a variety of benign and malignant hematological diseases. Previously, patients who underwent alloHCT were at high risk for complications with potentially life-threatening toxicities, including a variety of opportunistic infections as well as acute and chronic manifestations of graft-versus-host disease (GVHD), where the transplanted immune system can produce inflammatory damage to the patient. With recent advances, including newer conditioning regimens, advances in viral and fungal infection prophylaxis, and novel GVHD prophylactic and treatment strategies, improvements in clinical outcomes have steadily improved. One modality with great potential that has yet to be fully realized is targeting the microbiome to further improve clinical outcomes.In recent years, the intestinal microbiota, which includes bacteria, fungi, viruses, and other microbes that reside within the intestinal tract, has become established as a potent modulator of alloHCT outcomes. The composition of intestinal bacteria, in particular, has been found in large multicenter prospective studies to be strongly associated with GVHD, treatment-related mortality, and overall survival. Murine studies have demonstrated a causal relationship between intestinal microbiota injury and aggravated GVHD, and more recently, clinical interventional studies of repleting the intestinal microbiota with fecal microbiota transplantation have emerged as effective therapies for GVHD. How the composition of the intestinal bacterial microbiota, which is often highly variable in alloHCT patients, can modulate GVHD and other outcomes is not fully understood. Recent studies, however, have begun to make substantial headway, including identifying particular bacterial subsets and/or bacterial-derived metabolites that can mediate harm or benefit. Here, the authors review recent studies that have improved our mechanistic understanding of the relationship between the microbiota and alloHCT outcomes, as well as studies that are beginning to establish strategies to modulate the microbiota with the hope of optimizing clinical outcomes.

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Metagenomic Profiling of the Ocular Surface Microbiome in Patients After Allogeneic Hematopoietic Stem Cell Transplantation

Cited by 8 publications

References 39 publications

Longitudinal Changes of Ocular Surface Microbiome in Patients Undergoing Hemopoietic Stem Cell Transplant (HSCT)

Longitudinal Changes of Ocular Surface Microbiome in Patients Undergoing Hemopoietic Stem Cell Transplant (HSCT)

Recent advances in ocular graft-versus-host disease

The Microbiome and Its Impact on Allogeneic Hematopoietic Cell Transplantation

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