Toyoshima A, Noguchi N, Suzuki T
… +8 more, Kuroki T, Kagaya M, Oda F, Kono M, Sasaki J, Sasaki T, Saeki H, Osada SI
Exp Dermatol
· 2026 Feb · PMID 41652181
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Phosphatidylinositol-3 kinase (PI3K) is a central regulator of cell proliferation, survival, metabolism, and migration via the downstream AKT/mTOR pathway. Although activating mutations in the catalytic subunit of PI3Kα...Phosphatidylinositol-3 kinase (PI3K) is a central regulator of cell proliferation, survival, metabolism, and migration via the downstream AKT/mTOR pathway. Although activating mutations in the catalytic subunit of PI3Kα (p110α) have been documented in various cancers, including cutaneous squamous cell carcinoma (cSCC), the role of PI3Kγ (p110γ), which is predominantly expressed in immune cells, remains poorly defined in cSCC. To elucidate the function of p110γ in cSCC development, we compared tumour formation in wild-type and p110γ-deficient mice using both a chemical carcinogenesis model and a syngeneic cSCC cell implantation model. While genetic deletion or pharmacological inhibition of PI3Kγ did not affect keratinocyte proliferation or migration in vitro, p110γ-deficient mice exhibited significantly delayed tumour onset, reduced tumour burden, and suppressed growth of implanted cSCC tumours in vivo. Immunohistochemical analyses revealed that total CD4 T cell infiltration was unchanged, whereas CD8 cytotoxic T cell infiltration was markedly increased and FoxP3 regulatory T cells were significantly reduced in tumours from p110γ-deficient mice, resulting in a substantially elevated CD8/FoxP3 ratio. Immunoblot analyses of tumour lysates further demonstrated increased CD8 expression and enhanced NF-κB p65 phosphorylation in p110γ-deficient tumours. These results indicate that PI3Kγ contributes to cSCC development not by directly driving tumour cell proliferation but by shaping an immunosuppressive tumour microenvironment. Targeting PI3Kγ may therefore represent a promising immunotherapeutic strategy to enhance cytotoxic T-cell-mediated antitumour immunity in cSCC.
Systemic lupus erythematosus (SLE) is a chronic, heterogeneous autoimmune disease influenced by various genetic and environmental factors, and recent advances have established type I interferons (IFN-I) as pivotal driver...Systemic lupus erythematosus (SLE) is a chronic, heterogeneous autoimmune disease influenced by various genetic and environmental factors, and recent advances have established type I interferons (IFN-I) as pivotal drivers. This study comprehensively characterises IFN-I risk gene signatures in SLE. The IFN-I-related genes were obtained from GSE185047, and then Mendelian randomisation analysis using data from the FinnGen cohort (705 SLE cases, 385 509 controls) was utilised as a discovery set to identify IFN-I related risk genes. Single-cell RNA sequencing (scRNA-seq) and external cohorts were used to validate the four key signatures. Univariate and multivariate linear regression models assessed associations between gene expression and clinical parameters. DNA methylation analysis further evaluated epigenetic dysregulation in SLE immune subsets. Thirty-eight IFN-I-related genes were identified, and Mendelian randomisation analysis revealed robust causal associations between four genes (HERC5, IFIT3, IFI44L and IFI6) and SLE risk, with no heterogeneity or pleiotropy. ScRNA-seq demonstrated significant upregulation of these gene signatures in SLE PBMCs and monocytes (except IFIT3 in monocytes), along with altered immune cell proportions-specifically, increased monocytes and decreased T cells. External validation confirmed elevated expression of all four genes in SLE, with high diagnostic accuracy. Clinically, increased expression of these genes correlated with SLEDAI, reduced lymphocyte counts and lower complement C4 levels. Furthermore, DNA hypomethylation of IFI44L was observed across multiple SLE immune subsets, indicating epigenetic dysregulation. This study establishes HERC5, IFIT3, IFI44L and IFI6 as causal IFN-I risk genes in SLE and identifies IFI44L hypomethylation as a key epigenetic driver of IFN-I pathway activation. These findings offer new insights into SLE pathogenesis and highlight potential diagnostic biomarkers and therapeutic targets.
Currently, there is a lack of reliable laboratory tests for monitoring the severity of psoriasis and evaluating treatment efficacy. The neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) are nove...Currently, there is a lack of reliable laboratory tests for monitoring the severity of psoriasis and evaluating treatment efficacy. The neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) are novel parameters of systemic inflammation. This study aimed to evaluate the association between NLR, PLR and psoriasis. Databases were systematically searched for studies up to May 2025. Publications meeting any of the following criteria were eligible: (1) comparison of NLR and PLR between psoriasis patients and healthy controls, (2) correlation coefficient of NLR and PLR and Psoriasis Area Severity Index (PASI) score, and (3) NLR and PLR before and after 3-4 months of biologic therapies. The pooled results showed that the NLR and PLR were significantly higher in patients with psoriasis than in controls (standardised mean difference [SMD] = 0.645, 95% confidence interval [CI] 0.514-0.775; SMD = 0.467, 95% CI 0.304-0.630). Both NLR and PLR were significantly correlated with the PASI score (r = 0.214, 95% CI 0.178-0.250; r = 0.161, 95% CI 0.114-0.207). The NLR and PLR significantly decreased after receiving tumour necrosis factor-α blockers, ustekinumab, and interleukin-23 inhibitors for 3-4 months. The NLR and PLR may serve as convenient tools in monitoring psoriasis treatment and indicators of systemic inflammation.
Merkel cells (MCs) are connected to sensory fibres in the skin and contribute to tactile perceptions by acting as mechanoreceptors. MCs in the skin have been reported to be distributed in clusters or to be scattered. Whi...Merkel cells (MCs) are connected to sensory fibres in the skin and contribute to tactile perceptions by acting as mechanoreceptors. MCs in the skin have been reported to be distributed in clusters or to be scattered. While the structural characteristics of MCs may influence tactile perceptions, conventional studies using skin sections could only assess those structures in limited regions. Here, we conducted extensive three-dimensional observations of MCs in epidermal sheets and examined their clustering patterns based on intercellular distances. Skin specimens from female donors at different ages (27, 34, 62, 84 and 91 years old) varied in MC density ranging from 6.7 to 26.4 mm. Theoretically, a higher density of MCs would lead to the formation of short-distance clusters, but our results demonstrate that skin with the lowest MC density had a clustering pattern similar to skin with the highest MC density. These results indicate that inter-donor variation in MCs cannot be explained solely by uniform changes in MC density but rather reflects heterogeneous distribution patterns with distinct clustering configurations. Our pilot study provides insight into skin physiology and pathology by considering the spatial configuration of various types of skin cells, such as MCs, Langerhans cells and melanocytes.
Hidradenitis suppurativa (HS) is an autoinflammatory skin disease characterised by deep-seated and painful nodules, abscesses and draining tunnels that extensively penetrate the dermis in the axillae, inguinal and glutea...Hidradenitis suppurativa (HS) is an autoinflammatory skin disease characterised by deep-seated and painful nodules, abscesses and draining tunnels that extensively penetrate the dermis in the axillae, inguinal and gluteal areas. The exact aetiology remains unclear. However, current evidence suggests that HS originates from an intrinsic defect within the hair follicle, leading to follicular obstruction, cyst development and eventual rupture, which triggers an inflammatory reaction. The initiation, progression and maintenance of the disease may involve functional abnormalities in keratinocytes (KCs), significantly contributing to the production of proinflammatory cytokines within and around the affected tissue and increased infiltration of immune cells. This review synthesises current evidence on KCs in HS, emphasising their genetic background and metabolic dysregulation. It comprehensively evaluates the cytokine milieu influenced by KCs within affected tissues. Notably, it highlights the diverse phenotypes of KCs within draining tunnels, underscoring their heterogeneity and implications for disease progression.
Kageyama R, Ito T, Kurihara K
… +2 more, Fujiyama T, Honda T
Exp Dermatol
· 2026 Jan · PMID 41555493
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Alopecia areata is a typical skin disease with unmet needs. So far, it has been understood that the main cause of the intractability of chronic cases is the decrease in inflammatory cell infiltration and falling into the...Alopecia areata is a typical skin disease with unmet needs. So far, it has been understood that the main cause of the intractability of chronic cases is the decrease in inflammatory cell infiltration and falling into the telogen-like phase. However, in some cases, even in long-term chronic cases, inflammatory cell infiltration can be seen, so that we speculate that the long-term persistence of these perifollicular cells may be the reason for the lack of improvement as skin resident memory T (T) cells. To investigate the presence of T, nine treatment-resistant chronic AA patients and 5 acute AA patients were employed for staining with CD69 and CD103 as markers for identifying skin T cells. This study revealed the number of CD8CD103 T and CD69CD103 T cells tended to increase with increasing disease duration and refractoriness. In one case of AA refractory to conventional treatment, an oral JAK inhibitor (JAKi) showed dramatic efficacy with a reduction in the number of infiltrating CD103 cells, including CD8CD103 T and CD69CD103 T cells. These results suggest that refractory cases in the chronic phase tend to have more infiltrating skin T cells, and JAKi may be effective in the refractory cases of chronic AA.
Exp Dermatol
· 2026 Jan · PMID 41546170
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Matrix metalloproteinases (MMPs) are involved in the degradation of the extracellular matrix (ECM) and are found to participate in all stages of tumour progression including modifying signalling pathways, regulating cyto...Matrix metalloproteinases (MMPs) are involved in the degradation of the extracellular matrix (ECM) and are found to participate in all stages of tumour progression including modifying signalling pathways, regulating cytokines and promoting tumour growth, particularly by inducing angiogenesis and facilitating cancer spread. Extensive research has been concentrated on identifying and developing MMP inhibitors for cancer treatment, including melanoma, with particular focus on MMP-2, MMP-9 and MMP-14. MMP-2 and MMP-9 are gelatinases involved in collagen degradation, tumour invasion and angiogenesis, while MMP-14 activates other MMPs and promotes tumour cell migration. Early broad-spectrum MMP inhibitors showed limited success and significant side effects. However, selective MMP inhibitors offer a more targeted approach that may address these problems. By focusing on specific MMPs essential for melanoma invasion, metastasis and angiogenesis, these inhibitors have the potential to improve treatment efficacy and reduce the off-target effects seen with earlier broad-spectrum therapies. Recent years have seen a marked increase in studies on natural MMP inhibitors for melanoma, driven by their biocompatibility and reduced side effects. In addition to inhibiting MMPs, many of these inhibitors also provide antioxidant, anti-inflammatory and immune-modulatory benefits, thus enhancing their therapeutic potential and overall effectiveness in cancer treatment. These findings highlight the promising role of MMP inhibitors in melanoma therapy, suggesting a shift towards more targeted and combinatory treatment strategies. This review aims to provide an up-to-date overview of the advancements and therapeutic prospects of both synthetic and natural MMP inhibitors in melanoma treatment.
Psoriasis, a prevalent chronic inflammatory skin disease, substantially impairs patients' quality of life and is frequently linked to numerous systemic comorbidities. We aimed to investigate whether phenotypic age accele...Psoriasis, a prevalent chronic inflammatory skin disease, substantially impairs patients' quality of life and is frequently linked to numerous systemic comorbidities. We aimed to investigate whether phenotypic age acceleration (PhenoAge-accel) and obesity synergistically affect the risk of psoriasis. This analysis utilised data from 11 344 participants in the 2003-2006 and 2009-2010 cycles of the National Health and Nutrition Examination Survey (NHANES). Weighted multivariable logistic regression, along with subgroup and sensitivity analyses, was conducted to assess the combined influence of PhenoAge acceleration and body mass index (BMI) on psoriasis risk. At baseline, 307 participants were diagnosed with psoriasis. Both PhenoAge-accel and elevated body mass index (BMI) were associated with higher risks of psoriasis. After adjusting for potential confounders, compared to those in the BMI < 25 kg/m/PhenoAge-accel < 0 group, the odds ratios (95% CIs) were 1.07 (0.52-2.20), 1.32 (0.92-1.90), and 2.00 (1.44-2.77) for psoriasis in the BMI < 25 kg/m/PhenoAge-accel ≥ 0, BMI ≥ 25 kg/m/PhenoAge-accel < 0, and BMI ≥ 25 kg/m/PhenoAge-accel ≥ 0 groups, respectively. The results remain robust across a series of subgroups and sensitivity analysis. In conclusion, accelerated phenotypic age and obesity were synergistically associated with an increased risk of psoriasis.
The gut microbiota composition of patients with chronic spontaneous urticaria (CSU) has been shown to be different from that of healthy controls. However, whether the gut microbiome is different between CSU patients with...The gut microbiota composition of patients with chronic spontaneous urticaria (CSU) has been shown to be different from that of healthy controls. However, whether the gut microbiome is different between CSU patients with different treatment responses to omalizumab is seldom examined and is largely unknown. Antihistamine-refractory CSU patients were enrolled to receive three injections of omalizumab. The patients were divided into two groups based on their treatment responses to omalizumab determined using the weekly urticarial activity score. Demographic data, blood samples and faecal specimens were collected before, during and after omalizumab treatment. Faecal specimens underwent bacterial 16S ribosomal RNA sequencing to determine the gut bacterial microbiome. Serum biomarkers were examined using enzyme-linked immunosorbent assay. Fourteen patients were enrolled and were divided into two groups: complete responders (CRs) and non-complete responders (NCRs). At baseline, the α-diversity indices of the CR group were higher than those of the NCR group. The bacterial microbiota composition was different between the groups, but these differences became less obvious after omalizumab treatment. At baseline, the genera Bacteroides, Lactobacillus, Prevotella_9, Butyricimonas, Dialister, Megasphaera and Ruminococcaceae_UCG-002 were more abundant in the CR group. In addition, the changes in the IL-33 and IL-17 levels after omalizumab treatment were correlated with the changes in the relative abundances of Dialister (r = 0.929, p = 0.003) and Ruminococcaceae-UCG-002 (r = -0.828, p = 0.022), respectively. In conclusion, the CR patients' distinct and characteristic gut bacterial microbiota profile before treatment may contribute to their better responses to omalizumab.
Malovitski K, Rosenthal NK, Khair L
… +11 more, Hagin D, Freund T, Sharoni E, Peled A, Feller Y, Ishtewy R, Mohamad J, Sarig O, Samuelov L, Sprecher E, Pavlovsky M
Exp Dermatol
· 2026 Jan · PMID 41532450
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Abnormal NF-κB activity has been previously implicated in a range of immune-mediated disorders. Here, we aimed to elucidate the genetic basis underlying the co-occurrence of vitiligo, Addison's disease and granuloma annu...Abnormal NF-κB activity has been previously implicated in a range of immune-mediated disorders. Here, we aimed to elucidate the genetic basis underlying the co-occurrence of vitiligo, Addison's disease and granuloma annulare in a 43-year-old woman. Whole-exome sequencing identified a heterozygous splice-site variant (c.1364+1G>A, p.Met455fsTer1) in IKBKB, encoding the Inhibitor of κB kinase subunit beta (IKKβ), predicted to result in a premature stop codon. Immunoblotting of keratinocytes transfected with the mutant construct demonstrated the presence of a truncated form of IKKβ. Using a luciferase reporter assay under the control of NF-κB-responsive element, we demonstrated significantly reduced activity of the mutant protein compared to wild-type, supporting a loss-of-function mechanism. In line with this observation, the mutant protein was found to result in decreased expression levels of genes known to be regulated by NF-κB. Furthermore, HeLa cells transfected with the p.Met455fsTer1 variant or IKBKB-targeted siRNA exhibited markedly reduced levels of p105 and its processed form p50, compared with HeLa cells transfected with wild-type IKBKB or control siRNA, respectively. Collectively, these findings indicate that a loss-of-function effect in IKBKB may underlie the co-occurrence of a number of immune-mediated disorders through disruption of NF-κB signalling.
Pigmented diseases can significantly impact people's quality of life, with melanogenesis playing a key role. In this study, we first analysed the relationship between peroxisomes, peroxisomal biogenesis factor 16 (PEX16)...Pigmented diseases can significantly impact people's quality of life, with melanogenesis playing a key role. In this study, we first analysed the relationship between peroxisomes, peroxisomal biogenesis factor 16 (PEX16), and melanin synthesis using omics data and clinical samples. Our results showed that peroxisome function and PEX16 expression were negatively associated with melanogenesis. Overexpression of PEX16 in the melanin-producing MNT1 cell line resulted in an increase in peroxisome production and the inhibition of key genes related to melanogenesis, such as microphthalmia-associated transcription factor (MITF), tyrosinase (TYR), tyrosinase-related protein 1 (TYRP1), and dopachrome tautomerase (DCT). Consistently, when PEX16 was overexpressed in melanocytes, there was a significant reduction in melanin content. The expression of PEX16 was detected in skin tissues. We found that PEX16 expression was higher in the areas with relatively lower pigmentation and decreased following ultraviolet B (UVB) irradiation. Furthermore, our findings suggest that PEX16 can inhibit melanogenesis by suppressing the Wnt/β-catenin signalling pathway. In conclusion, PEX16 can inhibit the Wnt/β-catenin signalling pathway, thereby reducing melanogenesis. Our research provides new insights for the clinical diagnosis and treatment of skin pigmentation disorders.
Yamamoto T, Toyoshima R, Li L
… +3 more, Koyama A, Sato S, Shibata S
Exp Dermatol
· 2026 Jan · PMID 41518566
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Enhancer of Zeste Homologue 2 (EZH2) is an epigenetic regulator involved in immune cell differentiation and function; however, its role in psoriasis remains unknown. This study aimed to evaluate EZH2 expression in periph...Enhancer of Zeste Homologue 2 (EZH2) is an epigenetic regulator involved in immune cell differentiation and function; however, its role in psoriasis remains unknown. This study aimed to evaluate EZH2 expression in peripheral blood mononuclear cells from patients with psoriasis and explore its potential functional relevance to disease pathogenesis. Peripheral blood samples were obtained from 40 psoriasis patients and 18 healthy controls, and EZH2 expression in T cell and monocyte subsets was analysed by flow cytometry. EZH2 expression was significantly reduced in circulating CD8+ naïve and memory T cells, as well as in monocyte subsets from psoriasis patients compared to healthy controls. EZH2 levels in CD8+ naïve T cells showed a significant inverse correlation with disease severity scores. Functional analyses revealed that pharmacological EZH2 inhibition suppressed IL-17A expression in peripheral blood mononuclear cells under IL-23/IL-1β stimulation. In addition, immunofluorescence staining identified EZH2-positive T cells and monocytes within psoriatic skin lesions. Collectively, these findings suggest that EZH2 may be involved in the regulation of type 3 inflammatory responses and may therefore represent an epigenetic regulator contributing to psoriasis pathogenesis.
Fujimura T, Yoshino K, Kato H
… +24 more, Fukushima S, Fujisawa Y, Matsushita S, Uhara H, Rokunohe D, Takenouchi T, Maekawa T, Nakamura Y, Namikawa K, Takahashi A, Yoshikawa S, Iwata H, Yamasaki O, Uchi H, Ohno F, Ito T, Tanemura A, Ohe S, Yamazaki E, Takahashi-Watanabe M, Muto Y, Kambayashi Y, Hashimoto A, Asano Y
TM5614, a plasminogen activator inhibitor-1 (PAI-1) inhibitor, has demonstrated potential in overcoming nivolumab resistance in patients with unresectable, anti-PD-1 antibody-refractory malignant melanoma. Previous Phase...TM5614, a plasminogen activator inhibitor-1 (PAI-1) inhibitor, has demonstrated potential in overcoming nivolumab resistance in patients with unresectable, anti-PD-1 antibody-refractory malignant melanoma. Previous Phase II trials have shown promising response rates, warranting further investigation through a randomised, placebo-controlled Phase III trial. This Phase III, randomised, double-blind, placebo-controlled, investigator-initiated clinical trial aims to evaluate the efficacy and safety of TM5614 in combination with nivolumab for treating patients with unresectable, anti-PD-1 antibody-refractory malignant melanoma. The study will enrol 124 participants across 18 medical institutions in Japan. Patients will receive either TM5614 plus nivolumab or placebo plus nivolumab for 48 weeks. The primary endpoint is overall survival (OS), while secondary endpoints include objective response rate (ORR), progression-free survival (PFS), disease control rate (DCR), and the incidence of treatment-related adverse events. This study is designed to compare OS between the TM5614 plus nivolumab group and the placebo plus nivolumab group. Statistical analyses will be conducted using the Kaplan-Meier method and Cox proportional hazards models. This Phase III trial will provide critical insights into the efficacy of TM5614 in combination with nivolumab as a novel treatment strategy for unresectable, anti-PD-1 antibody-refractory malignant melanoma. The results may offer new therapeutic options to improve patient outcomes and overcome resistance to immune checkpoint inhibitors. TRIAL REGISTRATION: jRCT2021240049 (https://jrct.niph.go.jp/en-latest-detail/jRCT2021240049). Protocol version: Ver.1.2 (3rd February, 2025).
Folliculitis decalvans (FD) and lichen planopilaris (LPP) are classified as neutrophilic and lymphocytic cicatricial alopecias respectively. FD and LPP have distinctive clinical, trichoscopic and histopathological featur...Folliculitis decalvans (FD) and lichen planopilaris (LPP) are classified as neutrophilic and lymphocytic cicatricial alopecias respectively. FD and LPP have distinctive clinical, trichoscopic and histopathological features. Cases with concomitant or sequential features of both forms of primary cicatricial alopecia (PCA) have been described since 2020, and the term folliculitis decalvans and lichen planopilaris phenotypic spectrum (FDLPPPS) has been proposed. This study aimed to describe the clinicopathological features and response to treatment of patients who developed FDLPPPS in childhood. A retrospective review of patients with FDLPPPS with an age of onset of ≤ 18 years seen in three dermatology clinics in Australia and one in Lebanon from August 2020 to February 2024 was conducted. Fourteen patients (10 females and four males) with a mean (SD) age of onset of 12.4 (4.4) years were identified. Five patients had genetic or congenital abnormalities, and two patients were sisters. Scalp symptoms included itch (n = 8), pain or tenderness (n = 5) and flaking (n = 1), with clinical signs of crusting (n = 12), erythema (n = 10) and pustules (n = 3). Seven patients presented with a solitary plaque and seven with multiple plaques, most commonly affecting the vertex scalp (n = 13). Histopathological examination showed a perifollicular lymphocytic infiltrate and concentric lamellar fibrosis in 13 and 14 cases respectively. Keratosis pilaris (KP) or one of its variants was observed in eight cases. Treatment led to disease stabilisation in seven cases, but hair loss progressed in six cases. FDLPPPS is an aggressive form of primary cicatricial alopecia that can rarely begin in childhood. Given the clinical features and association with KP or its variants in a significant proportion of our patients, we hypothesise that FDLPPPS may be a sequela of a disorder of keratinisation.
The Mueller matrix has the capability of providing the complete polarisation information about the response of a medium to the incident polarised light. In this work, we report that the anisotropic structures of non-stai...The Mueller matrix has the capability of providing the complete polarisation information about the response of a medium to the incident polarised light. In this work, we report that the anisotropic structures of non-stained melanoma slices can be identified directly through the Mueller elements. It is observed that the elements M, M and M show a high degree of similarity with the three polarisation parameters (the x-y linear diattenuation, the x-y linear depolarization and the ±45° linear birefringence), with PSNR values of 33.4 dB, 35.7 dB and 40.0 dB, respectively. From images of M, M and M, the cell nuclei and intercellular stroma in the melanoma dermis can be identified with higher contrast. The values of these elements are specific: for the cell nuclei, M ranges from -0.75 to -0.27 and M ranges from -0.12 to -0.04; for the extracellular matrix, M, M and M fall within -0.16 and -0.07, 0.06 and 0.16 and 0.09 and 0.57, respectively. Finally, a theoretical analysis is presented to explain the observations. The results obtained in this is helpful for clinic applications of Mueller matrix images where a method of interpreting measured Mueller matrices rapidly and accurately is essential.
Acne and hidradenitis suppurativa (HS) are inflammatory disorders of the pilosebaceous unit that exhibit distinct clinical manifestations, indicating that they likely differ in their underlying pathophysiology. Microbial...Acne and hidradenitis suppurativa (HS) are inflammatory disorders of the pilosebaceous unit that exhibit distinct clinical manifestations, indicating that they likely differ in their underlying pathophysiology. Microbial dysbiosis is implicated in both diseases, yet direct comparisons using unified methods and analyses incorporating the oral microbiome are lacking. In this study, we collected lesional and nonlesional skin, buccal mucosa and faecal samples from 28 HS patients, 29 acne patients and 40 healthy controls, and profiled microbial communities using 16S rRNA V3-V4 sequencing with qPCR validation. HS lesions showed a pronounced enrichment of anaerobic Gram-negative taxa, including Prevotella, Porphyromonas and Fusobacterium, whereas acne lesions were dominated by Cutibacterium and Pseudomonas. Oral microbiome diversity was increased in both diseases, with HS showing distinct enrichment of Prevotella and Veillonella. HS patients also exhibited reduced gut microbial diversity. Correlation analyses revealed coordinated microbial alterations across the oral-gut-skin axis, and qPCR confirmed elevated concentrations of key anaerobes in HS. By directly comparing acne and HS across multiple anatomical sites, our study helps differentiate general inflammatory microbiome changes from those more specific to HS. The findings also suggest a potential oral-gut-skin microbial axis that may contribute to the chronic and destructive phenotype of HS, providing insights that could inform future microbiome-targeted therapeutic approaches.