Cutaneous T-Cell Lymphoma Skin Microbiome Is Characterized by Shifts in Certain Commensal Bacteria but not Viruses when Compared with Healthy Controls.
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ABSTRACT:
SUBMITTER: Harkins CP
PROVIDER: S-EPMC8124078 | biostudies-literature | 2021 Jun
REPOSITORIES: biostudies-literature
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Cutaneous T-Cell Lymphoma Skin Microbiome Is Characterized by Shifts in Certain Commensal Bacteria but not Viruses when Compared with Healthy Controls.
Harkins Catriona P CP MacGibeny Margaret A MA Thompson Katherine K Bubic Bianka B Huang Xin X Brown Isabelle I Park Jin J Jo Jay-Hyun JH Segre Julia A JA Kong Heidi H HH Rozati Sima S
The Journal of investigative dermatology 20201116 6
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Project description:The nasal microbiome of patients with cutaneous T-cell lymphoma (CTCL) remains unexplored despite growing evidence connecting nasal bacteria to skin health and disease. Nasal swabs from 45 patients with CTCL (40 with mycosis fungoides, 5 with Sézary syndrome) and 20 healthy controls from the same geographical region (Chicago Metropolitan Area, Chicago, IL) were analyzed using sequencing of 16S ribosomal RNA and tuf2 gene amplicons. Nasal α-diversity did not differ between mycosis fungoides/Sézary syndrome and healthy controls (Shannon index, genus level, P = 0.201), but distinct microbial communities were identified at the class (R2 = 0.104, P = 0.023) and order (R2 = 0.0904, P = 0.038) levels. Increased relative abundance of the genera Catenococcus, Vibrio, Roseomonas, Acinetobacter, and unclassified Clostridiales was associated with increased skin disease burden (P < 0.005, q < 0.05). Performed to accurately resolve nasal Staphylococcus at the species level, tuf2 gene amplicon sequencing revealed no significant differences between mycosis fungoides/Sézary syndrome and healthy controls. Although S. aureus has been shown to worsen CTCL through its toxins, no increase in the relative abundance of this taxon was observed in nasal samples. Despite the lack of differences in Staphylococcus, the CTCL nasal microbiome was characterized by shifts in numerous other bacterial taxa. These data add to our understanding of the greater CTCL microbiome and provide context for comprehending nasal-skin and host‒tumor‒microbial relationships.
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Project description:BackgroundCutaneous T-cell lymphoma (CTCL) patients often suffer from recurrent skin infections and profound immune dysregulation in advanced disease. The gut microbiome has been recognized to influence cancers and cutaneous conditions; however, it has not yet been studied in CTCL.ObjectivesTo investigate the gut microbiome in patients with CTCL and in healthy controls.MethodsA case-control study was conducted between January 2019 and November 2020 at Northwestern's busy multidisciplinary CTCL clinic (Chicago, Illinois, USA) utilizing 16S ribosomal RNA gene amplicon sequencing and bioinformatics analyses to characterize the microbiota present in fecal samples of CTCL patients (n = 38) and age-matched healthy controls (n = 13) from the same geographical region.ResultsGut microbial α-diversity trended lower in patients with CTCL and was significantly lower in patients with advanced CTCL relative to controls (P = 0.015). No differences in β-diversity were identified. Specific taxa were significantly reduced in patient samples; significance was determined using adjusted P-values (q-values) that accounted for a false discovery rate threshold of 0.05. Significantly reduced taxa in patient samples included the phylum Actinobacteria (q = 0.0002), classes Coriobacteriia (q = 0.002) and Actinobacteria (q = 0.03), order Coriobacteriales (q = 0.003), and genus Anaerotruncus (q = 0.01). The families Eggerthellaceae (q = 0.0007) and Lactobacillaceae (q = 0.02) were significantly reduced in patients with high skin disease burden.ConclusionsGut dysbiosis can be seen in patients with CTCL compared to healthy controls and is pronounced in more advanced CTCL. The taxonomic shifts associated with CTCL are similar to those previously reported in atopic dermatitis and opposite those of psoriasis, suggesting microbial parallels to the immune profile and skin barrier differences between these conditions. These findings may suggest new microbial disease biomarkers and reveal a new angle for intervention.
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Project description:This SuperSeries is composed of the SubSeries listed below.
2023-12-01 | GSE221150 | GEO
Project description:Mycosis fungoides (MF) is the most common entity of Cutaneous T cell lymphomas (CTCL) and is characterized by the presence of clonal malignant T cells in the skin. The role of the skin microbiome for MF development and progression are currently poorly understood. Using shotgun metagenomic profiling, real-time qPCR, and T cell receptor sequencing, we compared lesional and nonlesional skin of 20 MF patients with early and advanced MF. Additionally, we isolated Staphylococcus aureus and other bacteria from MF skin for functional profiling and to study the S. aureus virulence factor spa. We identified a subgroup of MF patients with substantial dysbiosis on MF lesions and concomitant outgrowth of S. aureus on plaque-staged lesions, while the other MF patients had a balanced microbiome on lesional skin. Dysbiosis and S. aureus outgrowth were accompanied by ectopic levels of cutaneous antimicrobial peptides (AMPs), including adaptation of the plaque-derived S. aureus strain. Furthermore, the plaque-derived S. aureus strain showed a reduced susceptibility towards antibiotics and an upregulation of the virulence factor spa, which may activate the NF-κB pathway. Remarkably, patients with dysbiosis on MF lesions had a restricted T cell receptor repertoire and significantly lower event-free survival. Our study highlights the potential for microbiome-modulating treatments targeting S. aureus to prevent MF progression.
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Project description:INTRODUCTION:The cutaneous microbiome maintains skin barrier function, regulates inflammation, and stimulates wound-healing responses. Burn injury promotes an excessive activation of the cutaneous and systemic immune response directed against commensal and invading pathogens. Skin grafting is the primary method of reconstructing full-thickness burns, and wound infection continues to be a significant complication. METHODS:In this study, the cutaneous bacterial microbiome was evaluated and subsequently compared to patient outcomes. Three different full-thickness skin specimens were assessed: control skin from non-burned subjects; burn margin from burn patients; and autologous donor skin from the same cohort of burn patients. RESULTS:We observed that skin bacterial community structure of burn patients was significantly altered compared with control patients. We determined that the unburned autologous donor skin from burn patients exhibits a microbiome similar to that of the burn margin, rather than unburned controls, and that changes in the cutaneous microbiome statistically correlate with several post-burn complications. We established that Corynebacterium positively correlated with burn wound infection, while Staphylococcus and Propionibacterium negatively correlated with burn wound infection. Both Corynebacterium and Enterococcus negatively correlated with the development of sepsis. CONCLUSIONS:This study identifies distinct differences in the cutaneous microbiome between burn subjects and unburned controls, and ascertains that select bacterial taxa significantly correlate with several comorbid complications of burn injury. These preliminary data suggest that grafting donor skin exhibiting bacterial dysbiosis may augment infection and/or graft failure and sets the foundation for more in-depth and mechanistic analyses in presumably "healthy" donor skin from patients requiring skin grafting procedures.
| S-EPMC5603347 | biostudies-literature
Project description:Introduction & hypothesisPrevious studies have suggested that women with urinary incontinence have an altered urinary microbiome. We hypothesized that the microbiome in women with mixed urinary incontinence (MUI) differed from controls and tested this hypothesis using bacterial gene sequencing techniques.MethodsThis multicenter study compared the urinary microbiome in women with MUI and similarly aged controls. Catheterized urine samples were obtained; v4-6 regions of the 16S rRNA gene were sequenced to identify bacteria. Bacterial predominance (> 50% of an individual's genera) was compared between MUI and controls. Bacterial sequences were categorized into "community types" using Dirichlet multinomial mixture (DMM) methods. Generalized linear mixed models predicted MUI/control status based on clinical characteristics and community type. Post-hoc analyses were performed in women < 51 and ≥ 51 years. Sample size estimates required 200 samples to detect a 20% difference in Lactobacillus predominance with P < 0.05.ResultsOf 212 samples, 97.6% were analyzed (123 MUI/84 controls, mean age 53 ± 11 years). Overall Lactobacillus predominance did not differ between MUI and controls (45/123 = 36.6% vs. 36/84 = 42.9%, P = 0.36). DMM analyses revealed six community types; communities differed by age (P = 0.001). A High-Lactobacillus (89.2% Lactobacillus) community had a greater proportion of controls (19/84 = 22.6%, MUI 11/123 = 8.9%). Overall, bacterial community types did not differ in MUI and controls. However, post-hoc analysis of women < 51 years found that bacterial community types distinguished MUI from controls (P = 0.041); Moderate-Lactobacillus (aOR 7.78, CI 1.85-32.62) and Mixed (aOR 7.10, CI 1.32-38.10) community types were associated with MUI. Community types did not differentiate MUI and controls in women ≥ 51 years (P = 0.94).ConclusionsWomen with MUI and controls did not differ in overall Lactobacillus predominance. In younger women, urinary bacterial community types differentiated MUI from controls.
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Project description:Microbiome of cutaneous SCC patients and controls
| PRJNA1231063 | ENA
Project description:BackgroundPsoriasis is a chronic inflammatory disease associated with systemic inflammation and comorbidities. Changes in the composition of the intestinal microbiome are involved in the pathogenesis of inflammatory diseases and metabolic syndrome. Characterizing the intestinal microbiome of patients with psoriasis may be relevant for the understanding of its clinical course and comorbidity prevention.ObjectiveTo characterize the intestinal microbiome of men with psoriasis compared to omnivore and vegetarian controls (without psoriasis).MethodCross-sectional study of 42 adult males: 21 omnivores with psoriasis; and controls: 14 omnivores and 7 vegetarian individuals. The characterization of the intestinal microbiome was performed by metagenomic analysis. Serum levels of lipopolysaccharide-binding protein (LPB) and C-reactive protein (CRP) were evaluated.ResultsThe groups differed from each other regarding nutritional aspects and microbiome; individuals with psoriasis had a higher consumption of protein and lower consumption of fibers. Levels of LPB, CRP, and the Firmicutes/Bacteroidetes ratio were higher in the group with psoriasis than in the vegetarian group (p<0.05). The genera Prevotella, Mogibacterium, Dorea, Bifidobacterium and Coprococcus, differed in the group with psoriasis compared to vegetarians; the genera Mogibacterium, Collinsella and Desulfovibrio differed from omnivores. A microbiome pattern linked to psoriasis (plsPSO) was identified, which was associated with higher LPB levels (rho=0.39; p=0.02), and lower dietary fiber intake (rho=-0.71; p<0.01).Study limitationsOnly adult men were evaluated.ConclusionA difference was identified in the intestinal microbiome of adult men with psoriasis when compared to healthy omnivores and vegetarian controls. The identified microbiome pattern was correlated with dietary fiber intake and serum levels of LPB.
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Project description:Post-traumatic stress disorder (PTSD) is a common mental health disorder that can occur following exposure to a traumatic event, and is characterized by symptoms including intrusive memories, dissociation, and nightmares. PTSD poses significant suffering on the individual and can reduce quality of life substantially, however, its mechanisms are not fully understood. It has also been associated with gut abnormalities, such as with irritable bowel syndrome, indicating possible involvement of the gut microbiome and gut-brain axis. Whereas previous research has implicated the gut microbiome and microbiome gut-brain axis in various mental health disorders, the relationship between gut microbiome function and PTSD is unclear. Specifically, little is known about whether specific gut microbiome compositions can increase the risk of developing PTSD, or, vice versa, act as a protective factor for the individual. This systematic review aims to synthesize the literature looking at gut microbiome differences between individuals with PTSD and trauma-exposed controls (TEC) while exploring potential risk and resilience factors for development of the disorder. Three studies met the inclusion criteria, and results showed that all studies found differences in gut microbial taxa between PTSD and TEC groups yet varied in their taxonomic level and type. One study found a significant difference in diversity between groups, reporting lower diversity in PTSD, and two studies found certain taxa to be correlated with PTSD symptom severity: Mitsuokella, Odoribacter, Catenibacterium and Olsenella genera, and Actinobacteria, Lentisphaerae and Verrucomicrobia phyla. This review has important implications for potential novel treatments for PTSD which target the gut microbiome, for example psychobiotic dietary interventions such as prebiotics and probiotics. It also informs our understanding of potential risk and resilience factors for the disorder, such as certain gut microbiome compositions being potentially protective or increasing susceptibility. More research is needed, as currently sample sizes are small and confounding variables (e.g., diet) are not always controlled for. Systematic review registration: The protocol was registered on PROSPERO, registration number: CRD42024530033.
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Project description:Background: Human HBV and HIV integrate their retro-transcribed DNA proviruses into the human host genome. Existing antiretroviral drug regimens fail to directly target these intrachromosomal xenogenomes, leading to persistence of viral genetic information. Retinazone (RTZ) constitutes a novel vitamin A-derived (retinoid) thiosemicarbazone derivative with broad-spectrum antiviral activity versus HIV, HCV, varicella-zoster virus and cytomegalovirus.Methods: The in vitro inhibitory action of RTZ on HIV-1 strain LAI, human HBV strain ayw, HCV-1b strain Con1, enhanced green fluorescent protein-expressing Ebola virus Zaire 1976 strain Mayinga, wild-type Ebola virus Zaire 1976 strain Mayinga, human herpesvirus 6B and Kaposi's sarcoma-associated herpesvirus replication was investigated. The binding of RTZ to human glucocorticoid receptor was determined.Results: RTZ inhibits blood-borne human HBV multiplication in vitro by covalent inactivation of intragenic and intraexonic viral glucocorticoid response elements, and, in close analogy, RTZ suppresses HIV-1 multiplication in vitro. RTZ disrupts the multiplication of blood-borne human HCV and Ebola Zaire virus at nanomolar concentrations in vitro. RTZ has the capacity to bind to human glucocorticoid receptor, to selectively and covalently bind to intraexonic viral glucocorticoid response elements, and thereby to inactivate human genome-integrated proviral DNA of human HBV and HIV.Conclusions: RTZ represents the first reported antiviral agent capable of eradicating HIV and HBV proviruses from their human host. Furthermore, RTZ represents a potent and efficacious small-molecule in vitro inhibitor of Ebola virus Zaire 1976 strain Mayinga replication.
| S-EPMC7714485 | biostudies-literature