Nasal Dysbiosis in Cutaneous T-Cell Lymphoma Is Characterized by Shifts in Relative Abundances of Non-Staphylococcus Bacteria

Hooper, Madeline; LeWitt, Tessa M.; Veon, Francesca L.; Pang, Yanzhen; Chlipala, George E.; Feferman, Leo; Green, Stefan J.; Sweeney, Dagmar; Bagnowski, Katherine; Burns, Michael B.; Seed, Patrick C.; Guitart, Joan; Zhou, Xiaolong

doi:10.1016/j.xjidi.2022.100132

Cited by 8 publications

(5 citation statements)

References 75 publications

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“…Therefore, we hypothesized that MF patients have a more signi cant disturbance of the skin microbiome beyond the mere presence of pathogenic microbes like S. aureus. So far, several reports characterized the MF skin microbiome [23][24][25][26][27] and indicated that (a) a destabilized microbiome and [23,28] (b) the abundance of certain microbial genera like Cutibacteria or Staphylococci [24,25] might be associated with disease severity. However, statistical signi cance was largely not reached, likely because of small sample sizes [24], characterization approaches that lacked resolution at the microbial species level, or because samples were not categorized based on clinical or lesional stages [28].…”

Section: Introductionmentioning

confidence: 99%

The Skin Microbiome Stratifies Patients with Cutaneous T Cell Lymphoma and Determines Event-Free Survival

Licht¹,

Dominelli²,

Kleemann

et al. 2023

Preprint

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Background: Cutaneous T cell lymphomas (CTCL) are a heterogeneous group of non-Hodgkin lymphomas that are characterized by the presence of clonal malignant T cells in the skin, with Mycosis fungoides (MF) being the most common entity. The role of the skin microbiome for MF development and progression are currently poorly understood. Methods: We used shotgun metagenomic profiling, real-time qPCR and T cell receptor sequencing to compare lesional and nonlesional skin of 20 patients with early and advanced MF that were treated at two independent German skin cancer centres. Additionally, Staphylococcus aureus and other bacterial species were isolated from MF skin for functional profiling and to investigate the S. aureus virulence factor spa. Results: We identified a subgroup of MF patients that exhibited a substantial dysbiosis on MF lesions with concomitant outgrowth of S. aureuson plaque while the other MF patients presented with a balanced microbiome on lesional skin. Dysbiosis and S. aureus outgrowth were accompanied with ectopic levels of cutaneous antimicrobial peptides (AMPs) and increased adaptation of the outgrowing, plaque-derived S. aureus strains, which may have resulted in or contributed to these microbiome perturbations. Furthermore, the plaque-derived S. aureus strains showed a reduced susceptibility towards antibiotics and an upregulation of the virulence factor spa, which also exhibited a potential gain-of-function mutation, that may render it highly potent to activate the NF-κB pathway. Last, we observed a restricted T cell receptor repertoire and a reduced event-free survival in patients with dysbiosis on MF lesions. Conclusions: Our data suggest that virulent, outgrowing S. aureus strains fuel pathogenesis in the MF patient subgroup with dysbiosis, possibly via highly potent spa that activates the NF-κB pathway. We therefore provide a solid basis for the role of the skin microbiome for MF progression and pave the way for potential microbiome modulating treatments specifically targeting S. aureus to prevent MF disease progression.

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Section: Introductionmentioning

confidence: 99%

The Skin Microbiome Stratifies Patients with Cutaneous T Cell Lymphoma and Determines Event-Free Survival

Licht¹,

Dominelli²,

Kleemann

et al. 2023

Preprint

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“…This work further contributes to a growing body of knowledge that suggests CTCL is a disease associated with global dysbiosis (10)(11)(12)(13)(14)(15)(16). The data herein support our previous findings on the CTCL gut microbiome, namely that patients with more advanced disease demonstrated decreased phylogenic diversity and loss of beneficial commensal taxa in comparison to healthy controls (11).…”

Section: Discussionmentioning

confidence: 68%

“…Broad-spectrum antibiotic treatment correlates with reduced tumor burden in some patients, and spontaneous CTCL mouse models exhibit mild, indolent disease when housed in germfree isolators but have rapid disease progression when moved to traditional housing (8,9). Recent work published by our group and others has demonstrated that CTCL patients are globally dysbiotic, with altered skin, gut, and nasal microbiomes (10)(11)(12)(13)(14)(15)(16)) and that dysbiosis worsens with disease severity (10-12, 16, 17).…”

Section: Introductionmentioning

confidence: 99%

Gut microbiota analyses of cutaneous T-cell lymphoma patients undergoing narrowband ultraviolet B therapy reveal alterations associated with disease treatment

Nguyen,

Chrisman,

Enriquez

et al. 2024

Front. Immunol.

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Recent studies have shown a close relationship between cutaneous T-cell lymphoma (CTCL) and its microbiome. CTCL disease progression is associated with gut dysbiosis and alterations in bacterial taxa parallel those observed in immunologically similar atopic dermatitis. Moreover, the microbial profile of lesional skin may predict response to narrowband ultraviolet B (nbUVB), a common skin-directed therapy. However, the relationship between the gut microbiome, an immunologically vital niche, and nbUVB remains unexplored in CTCL. Herein, we performed 16S rRNA sequencing and PICRUSt2 predictive metagenomics on DNA extracted from stool swabs of 13 CTCL patients treated with nbUVB, 8 non-treated patients, and 13 healthy controls. Disease response was assessed with modified Severity Weighted Assessment Tool (mSWAT); of nbUVB-treated patients, 6 improved (decreased mSWAT), 2 remained stable, and 5 worsened (increased mSWAT). Protective commensal bacteria including Lactobacillaceae and Erysipelatoclostridiaceae were significantly less abundant in CTCL patients compared to controls. With treatment, the CTCL gut microbiome exhibited decreased phylogenetic diversity and lower relative abundance of pro-inflammatory Sutterellaceae. Sutterellaceae was also significantly more abundant in patients who worsened, and Eggerthellaceae and Erysipelotrichaceae trended higher in patients who improved. Finally, PICRUSt2 functional predictions based on shifts in abundance of bacterial sequences repeatedly identified alterations in inositol degradation, which plays a key role in host immunomodulation, including inositol phospholipid signaling relevant to T-cell survival and proliferation. Our results bolster the paradigm of gut dysbiosis in CTCL and its functional implications in disease pathogenesis, and further delineate bacterial taxa associated with nbUVB response and with nbUVB treatment itself.

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“…The primers, 515F modified and 806R modified [7], contain 5 linker sequences compatible with Access Array primers for Illumina sequencers (Fluidigm, South San Francisco, CA, USA). PCRs were performed in a total volume of 10 microliters using MyTaq™ HS 2X Mix (Bioline, London, UK), primers at 500 nM concentration, and approximately 1000 copies per reaction of a synthetic double-stranded DNA template as described previously [8,9]. Thermocycling conditions were as follows: 95 • C for 5 (initial denaturation), followed by 28 cycles of 95 • C for 30 s, 55 • for 45 s, and 72 • C for 30 s. Each reaction's microliter of PCR product was transferred to the second-stage PCR reaction.…”

Section: Dna Extraction and 16s Rrna Gene Amplicon Sequencingmentioning

confidence: 99%

Temporal Changes in the Skin Microbiome of Epidermolysis Bullosa Patients following the Application of Wound Dressings

Horev,

Brandwein,

Vaknin

et al. 2023

JCM

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Objective: Epidermolysis bullosa (EB) is a group of rare hereditary skin disorders characterized by the formation of painful blisters, erosions, and ulcers. In addition, the wounds can easily become infected with different pathogens. Therefore, the dynamics in the microbial populations across the various stages of EB can shed light on pathophysiology, the effect of treatment, and the factors involved in its recovery, but they are understudied. We thus sought to characterize the skin microbiome among patients with EB over time. Methods: A prospective study conducted in the pediatric dermatology clinic at Soroka Medical Center, Beer-Sheva, Israel. Children (0–18) with simplex and recessive dystrophic EB were sampled at two different time points: before a therapeutic regimen and 90 days (±14 days) later. Samples were obtained from lesional skin (wound), healthy, non-lesional skin, and seborrheic skin (forehead). Samples were subject to 16S rRNA amplicon sequencing. Analyses performed included comparisons of relative abundance at the phyla and genera taxonomic levels, alpha and beta diversity comparisons, and differential abundance. Results: 32 children with EB were enrolled, for whom 192 skin microbiome samples were obtained. Lesional skin samples harbored significantly less Bacteroidota and Fusobacteriota before the initiation of treatment. Following topical dressing, we observed more Firmicutes and less Proteobacteria in lesional skin samples than healthy and seborrheic skin samples. In addition, Staphylococcus was significantly more abundant in lesional samples than in non-lesional and seborrheic samples following treatment. Conclusions: Our study recaptured the reduced bacterial diversity and increased staphylococcal carriage in EB patients, showing a potential effect of topical dressing either directly on the wound microbiome or indirectly through the contribution towards skin healing. The detection of Firmicutes in general, and S. aureus specifically, commensurate with the application of a wound dressing may warrant the use of additional treatment methods to facilitate wound healing. Future studies in these patients should prospectively correlate the temporal changes in the microbiome associated with various treatment modalities in order to optimize the care of EB patients.

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Nasal Dysbiosis in Cutaneous T-Cell Lymphoma Is Characterized by Shifts in Relative Abundances of Non-Staphylococcus Bacteria

Cited by 8 publications

References 75 publications

The Skin Microbiome Stratifies Patients with Cutaneous T Cell Lymphoma and Determines Event-Free Survival

The Skin Microbiome Stratifies Patients with Cutaneous T Cell Lymphoma and Determines Event-Free Survival

Gut microbiota analyses of cutaneous T-cell lymphoma patients undergoing narrowband ultraviolet B therapy reveal alterations associated with disease treatment

Temporal Changes in the Skin Microbiome of Epidermolysis Bullosa Patients following the Application of Wound Dressings

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