Search Results (145)

Atopic dermatitis (AD) and food allergy frequently coexist during early childhood and are increasingly linked through interactions within the gut–skin axis. We evaluated the clinical outcomes of an integrated nutritional and microbiome-oriented management strategy in children with food allergy-associated AD under real-world conditions. This prospective, two-center, real-world observational cohort study included 85 children (median age, 11 months) with AD diagnosed according to the Hanifin–Rajka criteria and confirmed IgE- and/or non-IgE-mediated food allergy. Participants received individualized nutritional and microbiome-oriented management comprising elimination diets, conventional topical therapy, microbiome-directed interventions, and nutritional supplementation tailored to their clinical, allergological, and microbiological profile. Disease severity was assessed using the Scoring Atopic Dermatitis (SCORAD) index at baseline and after approximately 1 and 3 months of follow-up. Cow’s milk, egg, and wheat were the predominant food allergens, and 69.4% of children were polyallergic. SCORAD decreased significantly during follow-up, with a mean relative reduction of 51.6% and 63.5% of participants achieving a SCORAD50 response. Food allergy burden independently predicted baseline disease severity, whereas documented gut dysbiosis was associated with polyallergy and greater absolute clinical improvement, although this association lost statistical significance after adjustment for baseline disease severity and should therefore not be interpreted as a favorable prognostic effect of dysbiosis. Baseline SCORAD remained the strongest independent predictor of clinical improvement. Integrated nutritional and microbiome-oriented management was associated with substantial clinical improvement and may represent a valuable adjunct to standard care in children with food allergy-associated AD. Because of the observational, uncontrolled design, these findings describe associations rather than causal treatment effects. These findings support further evaluation of personalized nutritional strategies in randomized controlled trials. Full article

Bioactive food ingredients that regulate the gut microbiota are promising dietary strategies for supporting systemic health, but their roles in skin photoaging remain insufficiently defined. Qiongyu Gao (QYG), a classical food–medicine homologous formula composed of Rehmanniae Radix, Panax ginseng, and Poria cocos, was evaluated as an oral functional food candidate for UV-induced skin photoaging. QYG was chemically characterized by HPLC and UPLC–QTOF–MS/MS. Young and aged mice were subjected to D-galactose plus UVA/UVB exposure and orally administered QYG, followed by skin transcriptomics, gut microbiota sequencing, serum metabolomics, and validation in UVB-injured primary dermal fibroblasts. QYG alleviated wrinkle formation, epidermal thickening, oxidative stress, inflammation, extracellular matrix degradation, collagen disorganization, and hyaluronic acid loss. Multi-omics analysis showed that QYG selectively remodeled gut microbiota, enriching Lactobacillus-, Bifidobacterium-, and Akkermansia-associated taxa, regulated serum metabolites related to energy and lipid metabolism, and enriched mitochondrial energy metabolism-related pathways in photoaged skin. In fibroblasts, QYG-containing serum restored mitochondrial membrane potential, reduced ROS accumulation and cellular senescence, and regulated AMPK/PGC-1α-associated markers. These findings support QYG as a promising food–medicine homologous functional food candidate for skin health maintenance through gut microbiota-associated systemic metabolic regulation. Full article

Background/Objectives: Atopic dermatitis (AD) is a chronic inflammatory skin disease in which gut–skin axis dysregulation is increasingly implicated. We conducted a prospective pilot study to describe the clinical evolution of pediatric AD following individualized, stool-guided microbiota-targeted therapy and to explore whether baseline dysbiosis markers predict outcomes beyond baseline disease severity. Methods: Twenty-one children with AD and laboratory-confirmed gut dysbiosis were enrolled consecutively at a tertiary pediatric center in Romania in a single-arm prospective pilot study. Gut microbiota was assessed using targeted culture-based stool analysis, generating a Flora Index and a binary High Putrefaction Flora classification. Individualized treatment consisted of strain-specific probiotics, prebiotics, and antifungals when indicated. Disease severity was assessed using the Patient-Oriented Eczema Measure (POEM) and Scoring Atopic Dermatitis (SCORAD) at baseline, 30 days, and 90 days. Longitudinal changes were evaluated using repeated-measures ANOVA and hierarchical regression models. Results: High Putrefaction Flora was present in 71.4% of participants. Mean POEM decreased from 14.67 ± 5.22 at baseline to 7.10 ± 3.82 at 90 days, while mean SCORAD decreased from 41.66 ± 15.28 to 17.93 ± 11.68 (both p < 0.001). Approximately 76% of participants achieved a ≥50% reduction in POEM, and 71% achieved a ≥50% reduction in SCORAD. Individualized microbiota-targeted therapy was associated with substantial improvements in both clinical and patient-reported disease severity over the 90-day follow-up. Although children with High Putrefaction Flora exhibited higher disease severity scores in unadjusted analyses, baseline disease severity was the only significant predictor of 90-day outcomes. The Flora Index provided no independent explanatory value. Conclusions: In this exploratory single-arm pilot study, individualized microbiota-targeted therapy was associated with substantial and clinically meaningful improvement in AD severity over 90 days. Dysbiosis markers were associated with disease burden but did not independently predict outcomes, suggesting that they may function primarily as indicators of baseline severity rather than prognostic biomarkers. Because of the uncontrolled study design, causal inferences regarding treatment effects cannot be made, and these findings should be considered hypothesis-generating. Adequately powered randomized controlled trials are required to determine the efficacy of individualized microbiota-targeted interventions in pediatric atopic dermatitis. Full article

Atopic dermatitis (AD) is a chronic inflammatory skin disease characterized by epidermal barrier dysfunction, immune dysregulation, and marked clinical heterogeneity. Growing evidence implicates the gut microbiome in AD-related pathways through microbial metabolites, intestinal barrier function, and systemic immune signaling. This narrative review synthesizes current evidence on gut microbial alterations in AD, with particular attention to short-chain fatty acids, tryptophan-derived aryl hydrocarbon receptor ligands, intestinal permeability, gut–skin microbiome interactions, and microbiota-targeted interventions. Human studies have reported associations between AD and altered abundance of selected microbial taxa, metabolite profiles, and markers of intestinal barrier dysfunction, whereas animal and in vitro studies provide complementary mechanistic evidence. However, findings remain heterogeneous across age groups, disease phenotypes, geographic populations, analytical platforms, and treatment exposures, and causality is incompletely established. Probiotic and synbiotic interventions have shown strain-specific and context-dependent effects, while postbiotics, fecal microbiota transplantation, washed microbiota transplantation, and metabolite-directed approaches remain investigational. AI-assisted multi-omics methods may improve biological stratification and hypothesis generation, but current applications are limited by small sample sizes, cohort heterogeneity, overfitting, insufficient external validation, and limited clinical implementation. Current evidence therefore supports the gut microbiome as a mechanistically plausible contributor, potential biomarker, and therapeutic target in AD while underscoring the need for longitudinal, phenotype-aware, and externally validated studies before routine clinical translation. Full article

Interactions among the gut, brain, and skin are increasingly understood as a systemic regulatory network connecting intestinal activity, neuroimmune communication, and cutaneous homeostasis. Microbiota-derived metabolites, immune mediators, and neuroendocrine pathways can influence central nervous system activity and subsequently regulate skin homeostasis. This review summarizes current evidence on how functional ingredients modulate the gut–brain–skin axis in the context of aging and skin health. Polyphenols, probiotics, and omega-3 fatty acids appear to act through overlapping biological routes, including reshaping microbial communities, supporting epithelial barrier function, regulating immune activity, and limiting oxidative stress. These gut-derived signals may affect the brain through neural, endocrine, and immune pathways, thereby modulating neuroinflammation, hypothalamic–pituitary–adrenal (HPA) axis activity, and neurotransmitter balance. Through brain–skin communication, these changes may influence inflammation, epidermal barrier integrity, collagen remodeling, and skin aging processes. Emerging clinical evidence suggests potential improvements in skin-related outcomes and systemic inflammatory markers; however, studies remain heterogeneous, and integrated assessments of gut, brain, and skin endpoints are limited. Further studies that integrate multi-omics profiling with carefully designed clinical trials will be required to define causal pathways and support the development of evidence-based nutritional approaches targeting this axis. Full article

Atopic dermatitis (AD) is a prevalent chronic inflammatory skin disorder driven by epidermal barrier defects and dysregulated Th2 cell responses. While therapies primarily address adaptive immunity, the role of Natural Killer (NK) cells remains underappreciated. This review analyzes NK cell dysfunctions in AD pathogenesis, evaluating their contributions to compromised skin immunity, microbial dysbiosis, and secondary infections. Accumulating evidence reveals a systemic deficiency of mature, cytotoxic CD56^dim and NKp80+ NK cell subsets in peripheral blood, correlating with disease severity. Within the cutaneous microenvironment, Staphylococcus aureus subverts defenses by utilizing leukocidins to lyse mature NK cells, while superantigens drive an aberrant, pro-inflammatory CD57⁻NKG2+ phenotype, exacerbating inflammation. Furthermore, localized exhaustion of functional NK cells and failure to produce interferon-gamma directly explains AD patients’ unique susceptibility to severe viral complications like eczema herpeticum. Importantly, treatments such as dupilumab and gut microbiota transplantations demonstrate that these NK cell aberrations are reversible, shifting immunity toward a normalized regulatory state. In conclusion, the NK cell compartment represents a vital regulatory axis bridging innate and adaptive immunity. Targeting this axis, particularly through IL-15 superagonists, offers a promising therapeutic frontier to suppress type 2 inflammation and restore antimicrobial defenses. Full article

Background: Skin aging is influenced by intrinsic and extrinsic factors, and growing evidence suggests that nutritional interventions, particularly probiotics, may modulate key biological pathways involved in skin barrier function, hydration, and oxidative stress through the gut–skin axis. Methods: In this randomized, double-blind, placebo-controlled clinical trial, 66 adults received a probiotic formulation containing Lacticaseibacillus rhamnosus LRH020, Lactiplantibacillus plantarum PBS067, and Limosilactobacillus reuteri PBS072 for 56 days, followed by a 28-day follow-up. Skin structure, function, and oxidative status were assessed using 3D profilometry, high-frequency ultrasound, corneometry, transepidermal water loss (TEWL), FRAP assay, and expert clinical scoring. Results: Compared with placebo, the probiotic group showed significant improvements in wrinkle depth (−15.0% at T56), and roughness (−6.1% at T56). Moreover, other skin parameters were significantly enhanced by the end of treatment, including greater skin density, hydration, and antioxidant capacity, alongside a reduction in TEWL. Improvements persisted at follow-up, suggesting a durable, lasting benefit of the probiotic formulation beyond the treatment period. Conclusions: These findings support the role of targeted probiotic supplementation as a promising strategy to improve structural, functional, and oxidative markers of skin aging. Full article

Atopic dermatitis (AD) is a chronic inflammatory skin disorder characterized by epithelial barrier dysfunction, immune dysregulation, and marked clinical heterogeneity. Although sex hormones and gut microbiota have independently been implicated in AD, their potential interactions remain incompletely understood. This narrative review integrates evidence from clinical, experimental, and preclinical studies examining the interplay among progesterone, testosterone, gut microbiota, and AD, with emphasis on immune regulation, epithelial barrier function, and gut–skin communication. Overall, the available evidence suggests that progesterone is predominantly associated with type 2 immune responses, alterations in epithelial barrier homeostasis, and context-dependent microbial remodeling. In contrast, physiological testosterone is generally associated with immunoregulatory effects and microbial profiles enriched in short-chain fatty acid-producing bacteria, whereas local androgen metabolism may contribute to skin barrier dysfunction. Current evidence also supports a bidirectional relationship between gut microbiota and sex hormones, whereby hormonal fluctuations influence microbial composition while microbial metabolism may modify steroid hormone bioavailability. Collectively, these findings support an integrated endocrine–microbial–immune framework that may contribute to AD beyond cutaneous inflammation. Although direct evidence simultaneously evaluating these components remains limited, this framework may help explain sex-specific differences in disease susceptibility, severity, and clinical course while guiding future mechanistic studies of the hormone–gut microbiota–skin axis. Full article

The skin microbiome is essential for epidermal barrier integrity and immune homeostasis. This review explores the therapeutic shift in dermo-cosmetics toward probiotic, prebiotic, synbiotic, and postbiotic strategies for managing wound healing, “inflammaging”, and chronic dermatoses like acne, atopic dermatitis (AD), psoriasis, and rosacea. Mechanisms include gut–skin axis modulation, competitive pathogen exclusion, and the suppression of inflammatory pathways (e.g., NF-κB). While live probiotics demonstrate high clinical efficacy, their formulation is severely hindered by standard cosmetic preservatives and manufacturing thermal stress. Consequently, evidence suggests inanimate postbiotics have emerged as promising, stable alternatives, which may offer antimicrobial and tissue-repairing benefits without strict cold-chain requirements. However, the industry faces significant regulatory ambiguity and “probiotic-washing”, with most commercial products mislabeling postbiotic lysates as live cultures. Advancing this field requires standardized sampling protocols and transparent labeling. Ultimately, precision dermatology is likely to be driven by AI-assisted microbiome profiling, synthetic biology, and advanced delivery matrices (e.g., electrospun nanofibers, alginate microencapsulation), transforming skincare from reactive treatments into proactive, targeted ecological management. Full article

Emerging research highlights the complex interplay between the gut microbiome, skin health, and environmental exposures, forming what is now recognized as the gut–skin–exposome axis. This narrative review explores the role of gut microbiome dysbiosis—a disruption in the balance of intestinal microorganisms—in the pathogenesis and progression of various non-communicable inflammatory skin diseases, including acne, atopic dermatitis, psoriasis, rosacea, systemic lupus erythematosus, chronic spontaneous urticaria, hidradenitis suppurativa, and alopecia areata. This review synthesizes mechanistic studies, clinical trials, and Mendelian randomization data to elucidate how altered gut microbial composition contributes to systemic and cutaneous inflammation. Key modifiable factors, such as diet, antibiotics, stress, and sleep, as well as interventions like probiotics, prebiotics, synbiotics, and fecal microbiota transplantation, are discussed for their potential therapeutic value. By integrating clinical insights with microbiome science, this review underscores the importance of a holistic, systems-based approach in managing inflammatory skin diseases, offering clinicians evidence-based strategies to improve patient outcomes through gut microbiome modulation. Full article

Postbiotics are increasingly recognized as a predominant group of biotherapeutic agents sourced from the microbial secretome, offering functional benefits, while circumventing the safety concerns associated with the application of live microbial consortia. These microbial derivatives are emerging as promising approaches for tackling complex diseases, encompassing cancer, autoimmune diseases, and metabolic disorders, through modulation of host cell signalling pathways, including G protein-coupled receptors (GPCRs), the NF-κB (Nuclear Factor Kappa B) pathway, and epigenetic regulatory pathways. Besides systemic effects, postbiotics may also have localized effects, such as epithelial regeneration, modulation of fibroblast functions, and control of collagen remodelling. Eventually, the scale-up in the production of postbiotics has initiated new avenues in improving sustainable agriculture and environmental biotechnology. This comprehensive review attempts to integrate mechanistic insights and translational applications, highlighting the therapeutic potential of postbiotics across biomedical and ecological domains. These observations could pave the way to bridge the gap between microbiome regulation, precision medicine, and sustainable biotechnology, thereby positioning postbiotics as a versatile tool addressing some of the most pressing health and sustainability challenges of the 21st century. Full article

Background: Rosacea is a chronic inflammatory dermatosis with emerging links to the gut–skin axis, yet integrative data connecting fecal microbiota with metabolic and immune parameters remain scarce. Methods: Within a cohort of Croatian women (N = 300, aged 30–35), participants with self-reported physician-diagnosed rosacea (n = 19) were compared to controls (n = 281). Assessments included validated questionnaires, anthropometrics, fasting blood parameters, and fecal 16S rRNA gene sequencing (QIIME2). Taxonomic profiling at four levels (899 features) used Mann–Whitney U tests with per-level Benjamini–Hochberg FDR correction. This study follows STROBE and STORMS guidelines. Results: On the host side, rosacea was nominally associated with higher BMI (p = 0.037), poorer sleep quality (p = 0.038), elevated monocytes (p = 0.031), and higher HOMA-B (p = 0.013); these comparisons were not corrected for multiple testing. Fecal 16S rRNA analysis (rosacea n = 18, controls n = 265) identified 15 nominally significant genera, including depleted Bifidobacterium (p = 0.007), Roseburia (p = 0.033), and enriched Anaerostignum (p < 0.001). However, no taxon survived FDR correction at any taxonomic level (lowest q = 0.165), and the total number of nominally significant features (48/899, 5.3%) did not exceed chance expectation (binomial p = 0.340). All key taxa remained nominally significant after BMI adjustment. An exploratory Random Forest classifier (five genera + HOMA-B + cortisol) achieved LOOCV AUC = 0.785, but feature selection on the training data limits interpretation. Conclusions: In this narrowly age-defined female cohort, host-side metabolic and immune differences reached nominal significance without multiple-testing correction. Fecal microbiota differences were exclusively exploratory: no taxon survived FDR correction, and the overall signal did not exceed chance expectation. The pattern of findings is compatible with—but does not constitute evidence for—a gut–skin axis contribution to rosacea. Confirmation in adequately powered cohorts with clinical rosacea verification, comprehensive confounder capture, and pre-registered analyses is required before any mechanistic or clinical conclusions can be drawn. Full article

Background and Clinical Significance: Cutaneous paraneoplastic phenomena are infrequently characterised in colorectal cancer (CRC), and chronic pruriginous inflammatory eruptions in particular have received limited attention. In older adults, persistent treatment-resistant dermatoses of unclear aetiology may represent overlooked extraintestinal diagnostic clues to occult malignancy, including potentially curable CRC. Faecal immunochemical testing (FIT) for occult bleeding is a low-cost, non-invasive tool whose role outside conventional alarm-symptom triage remains underexplored. Case presentation: A 72-year-old woman presented for outpatient evaluation with several months of pruriginous, pustular, and crusted symmetric eruption involving the dorsal aspects of the limbs, refractory to standard dermatologic treatment, and without gastrointestinal symptoms. A non-invasive systemic stool-based work-up demonstrated detectable faecal haemoglobin (iFOBT), mildly elevated faecal calprotectin (51.6 mg/kg, ULN 50 mg/kg), markedly elevated faecal alpha-1-antitrypsin (631 µg/mL; 2.3× ULN), and predominance of Escherichia coli on stool culture. Colonoscopy revealed a locally advanced rectal adenocarcinoma; staging classified the lesion as cT3N1M0. The patient received long-course neoadjuvant chemoradiotherapy (50 Gy, concurrent capecitabine) followed by low anterior resection with total mesorectal excision and pathological complete response (ypT0N0, R0), and adjuvant capecitabine. The cutaneous eruption resolved progressively in parallel with antineoplastic therapy without specific dermatologic intervention. The patient remains in remission at over 36 months. Conclusions: Persistent, unexplained, treatment-resistant pruriginous/pustular cutaneous eruptions may, in selected patients, coincide with an underlying malignancy, including colorectal cancer, and should prompt careful individualised clinical assessment, including review of age-appropriate colorectal cancer screening status. This single case raises the hypothesis that quantitative faecal immunochemical testing (FIT) may be prospectively evaluated as a low-cost, non-invasive triage tool in carefully selected patients aged ≥50 years with persistent dermatoses of unclear aetiology, even in the absence of gastrointestinal symptoms. Positive FIT results should be managed according to established local colorectal referral pathways. NICE diagnostics guidance DG56 supports FIT use in symptomatic adults with suspected lower gastrointestinal pathology; however, any extension of FIT to extraintestinal presentations remains investigational and requires formal validation through prospective studies assessing diagnostic yield, cost-effectiveness, and stage distribution. Full article

The skin is a complex immunological organ in which reactive oxygen species (ROS)-related pathways and host–microbe interactions synergically maintain immune homeostasis. Dysregulation of several oxidative mechanisms, including lipid peroxidation, mitochondrial dysfunction, ferroptosis, and impaired antioxidant defenses, alongside gut microbiome imbalance, is increasingly recognized as a key modulator of the immune response involved in disease onset and progression. However, their role in immune-mediated dermatoses remains incompletely defined. This narrative review aims to provide a comprehensive overview of the contribution of these altered pathways to the pathogenesis and prognosis of the major immune-mediated skin diseases. Across all conditions examined, elevated oxidative biomarkers, such as malondialdehyde (MDA), advanced glycation end-products (AGEs), advanced oxidation protein products (AOPPs), 8-hydroxydeoxyguanosine (8-OHdG), and reduced antioxidant capacity are consistently reported. Ferroptosis, driven by iron-dependent lipid peroxidation and dysfunction of Glutathione peroxidase 4 (GPX4), emerges as a relevant cell death pathway, particularly in psoriasis and atopic dermatitis (AD). In parallel, dysbiosis of the gut and skin microbiomes, characterized by depletion of short-chain fatty acid (SCFA)-producing taxa such as Faecalibacterium prausnitzii, Bifidobacterium, and Akkermansia muciniphila, has been reported across multiple diseases. Particular attention is given to shared molecular axes, such as the disruption of epithelial barrier integrity, activation of innate and adaptive immune responses, and the role of microbial-derived metabolites in modulating redox signaling, unraveling a bidirectional crosstalk. Emerging therapeutic strategies targeting these bidirectional crosstalks show biological plausibility and promising preliminary results. Integrating redox and microbial profiling into clinical practice may improve patient stratification and foster the development of more personalized therapeutic approaches beyond conventional immunological treatments. Full article

Sensory neurons at barrier tissues were once seen as passive detectors of environmental stimuli. However, in the last five years, increasing evidence has challenged this view, redefining these cells as active immune sentinels that directly affect tissue immunity in the skin, lungs, and gastrointestinal tract. Nociceptors and pruriceptors express various immune-sensing receptors, including Toll-like receptors, cytokine receptors, and alarmin sensors, which allow them to directly detect pathogens, allergens, and tissue damage. When activated, sensory neurons quickly release neuropeptides such as calcitonin gene-related peptide (CGRP), substance P, vasoactive intestinal peptide (VIP), and PACAP (pituitary adenylate cyclase-activating polypeptide), which guide immune cell recruitment, activation, and resolution. Reciprocally, immune-derived mediators, including IL-33, IL-31, thymic stromal lymphopoietin (TSLP), IL-4/IL-13, and TNF-α, modulate neuronal excitability and plasticity, forming bidirectional neuroimmune circuits that control inflammation, host defense, pain, and itch. Landmark studies published in 2024–2025, including neuronal control of gut Treg function and the identification of sensory nerve immune niches, have further refined this framework and revealed tissue-specific circuit specialization. This review synthesizes recent insights from molecular, cellular, and systems levels into the sensory neuroimmune axis, emphasizes its protective versus pathogenic roles, and critically evaluates emerging therapeutic strategies and safety concerns, positioning sensory neuroimmunology as a unifying framework for tissue barrier homeostasis and disease. Full article