The skin microbiota, with its millions of bacteria, fungi, and viruses, plays a key role in balancing the health of the skin and scalp. Its continuous exposure to potentially harmful stressors can lead to abnormalities such as local dysbiosis, altered barrier function, pathobiont overabundance, and infections often sustained by multidrug-resistant bacteria. These factors contribute to skin impairment, deregulation of immune response, and chronic inflammation, with local and systemic consequences. In this scenario, according to the needs of the bio-circular-green economy model, novel harmless strategies, both for regulating the diverse epidermal infectious and inflammatory processes and for preserving or restoring the host skin eubiosis and barrier selectivity, are requested. Vitis vinifera L. leaves and their derived extracts are rich in plant secondary metabolites, such as polyphenols, with antioxidant, anti-inflammatory, antimicrobial, and immunomodulatory properties that can be further exploited through microbe-driven fermentation processes. On this premise, this literature review aims to provide an informative summary of the most updated evidence on their interactions with skin commensals and pathogens and on their ability to manage inflammatory conditions and restore microbial biodiversity. The emerging research showcases the potential novel beneficial ingredients for addressing various skincare concerns and advancing the cosmeceutics field as well.

SUMMARY: Atopic dermatitis (AD) is a prevalent chronic inflammatory skin disorder, affecting 10%–20% of the population, characterized by dryness, intense itching, and recurrent rashes. The pathophysiology of AD is multifactorial, involving skin barrier dysfunction, immune dysregulation, genetic factors (such as filaggrin mutations), and environmental factors. The skin microbiota also plays a pivotal role in AD, serving both as a target and a driver of the disease. In AD, the delicate balance of the skin microbiota is disrupted, leading to a decrease in beneficial bacteria such as Streptococcus , Cutibacterium , and Corynebacterium . Concurrently, bacterial pathobionts, notably Staphylococcus aureus , proliferate and express their virulence factors excessively. This imbalance exacerbates symptoms by damaging the skin barrier, releasing toxins, and triggering a Th2-driven immune response, thus weakening the skin defenses and making individuals with AD more susceptible to bacterial, fungal, and viral infections, thereby complicating treatment and worsening disease outcomes. Effective AD management requires a thorough understanding of the interplay among the skin microbiota, the immune system, and microbial pathobionts. Strategies that restore the microbial balance, preserve the skin barrier, and modulate the immune response show significant potential for reducing infections and improving AD symptoms, highlighting the microbiota’s dual role in AD pathology. This review examines the complex role of the skin microbiota in AD, emphasizing how dysbiosis both drives disease progression and influences immune responses, and vice versa. It also explores emerging microbiota-targeted therapies aimed at improving disease outcomes.

Atopic dermatitis (AD) is a chronic inflammatory skin disorder influenced by both genetic and environmental factors, collectively termed the exposome. Among these determinants, diet emerges as a pivotal component, with diverse nutrients, contaminants, and additives shaping immune responses, microbiota composition, and systemic inflammatory status. This literature review aimed to elucidate the interplay between dietary factors and skin dysbiosis in AD, providing insights into how these interactions may impact disease susceptibility and progression. A comprehensive search of PubMed and Scopus was conducted using relevant keywords and medical subject headings (MeSH). Studies published in English within the past 25 years were included, encompassing in vitro, in vivo, and ex vivo research, as well as reviews. Priority was given to frequently cited articles, reflecting significant contributions to current understanding. Findings suggest that dietary habits influence AD by modulating both gut and skin microbiota, immune pathways, and inflammatory processes. These insights underscore the importance of considering diet within a broader exposome framework, paving the way for targeted interventions to improve AD management. Further research is needed to clarify the mechanisms and optimize nutritional strategies, potentially informing preventive and therapeutic approaches for AD.

Vitis vinifera L. leaves represent one of the most phenolic-rich grapevine biomasses, exhibiting a broad spectrum of biological activities, including prebiotic and microbiota-modulating ones. However, as they are mainly regarded as agro-industrial waste, they are still an underexploited resource. Probiotic-driven fermentation may offer a promising strategy to enhance their bioactive potential while addressing this challenge. The aim of this study was to evaluate the effects of the in vitro fermentation of Vitis vinifera L. leaf extract (VVLE) by Lactiplantibacillus plantarum PBS067 in terms of phenolic content, antioxidant activity, lactic acid and protein content, and metabolomic profile. Our analysis shows the prebiotic activity of VVLE, as VVLE-supplemented medium allowed probiotic growth without toxic effects. Leaves fermentation led to a significant enrichment in lactic acid and the biotransformation of complex plant-secondary metabolites into smaller derivatives. However, VVLE antioxidant capacity slightly decreased after the fermentation, likely due to the phenolic conversion itself. These results highlight how controlled lacto-fermentation valorizes grapevine leaves, transforming them into sustainable upcycled bioactive products with potential applications within cosmetics, pharmaceuticals, nutraceuticals and complementary medical product sectors. Key points: • L. plantarum PBS067 thrives in medium supplemented with polyphenol-rich leaf extract • L. plantarum PBS067-driven fermentation modulates VVLE phytochemical profile • L. plantarum PBS067-driven fermentation valorizes viticulture by-products

Oral lichen planus (OLP) is a chronic inflammatory oral disease associated with immune dysregulation and malignant transformation risk. Vitamin D and probiotics may modulate immune and microbial pathways involved in OLP. In this study, we evaluated their effects on clinical outcomes and multi-omics profiles in 25 adult OLP patients (median age: 68 years). Vitamin D-deficient patients received 2000 IU/day vitamin D3, and all participants received a probiotic blend (Limosilactobacillus reuteri LRE11, Lacticaseibacillus rhamnosus LR04, and Lacticaseibacillus casei LC04) for 16 weeks. Clinical assessments and analyses of saliva, serum, oral swabs, and stool samples were performed before and after treatment. Clinical outcomes improved significantly, with reductions in lesion number (p < 0.001), lesion size (p = 0.004), and bleeding lesions (p = 0.014); 76% of patients were classified as in remission. Vitamin D levels increased significantly among deficient patients receiving correction (p < 0.01). Salivary and fecal metabolomics showed significant remodeling of amino acid and carbohydrate pathways, including decreases in branched-chain amino acids in saliva and modulation of nicotinamide- and amino acid-related metabolites in feces. Microbiome α-diversity remained stable, whereas β-diversity shifted significantly across oral and fecal sites, with enrichment of Lacticaseibacillus and other context-dependent commensals. Multi-omics integration identified three latent factors linking salivary cytokines, microbial taxa, metabolites, and systemic lipid profiles, suggesting coordinated mucosal–metabolic–immune remodeling across the oral–gut axis.

Atopic dermatitis (AD) is a chronic inflammatory skin disease often requiring systemic biological therapies, such as the IL-4/IL-13 inhibitor Dupilumab, for long-term disease control. While Dupilumab is highly effective in restoring the skin barrier and reducing clinical severity, systemic complications may occur. We report a 62-year-old female with severe AD longitudinally monitored during Dupilumab treatment at baseline (T0), week 4 (T4), week 8 (T8), and week 16 (T16). Clinical assessments were performed at all visits, while microbiological, cytokine, metagenomic, and metabolomic analyses were conducted at T0, T8, and T16. The patient showed rapid clinical improvement at T4, followed by an abrupt transient worsening associated with an intercurrent S. aureus sepsis, and sustained improvement by T16, with EASI decreasing from 50.4 to 20. Despite the systemic inflammatory surge, no cutaneous relapse was documented. Multi-omics profiling highlighted a distinct immunological decoupling: while skin S. aureus load and type 2 inflammatory markers (IL-13, IL-31) progressively declined, a sharp surge in systemic pro-inflammatory cytokines (TNF-alpha) was observed at week 16, temporally associated with the septic episode. This case illustrates how longitudinal multi-omics profiling may uncover clinically silent systemic immune alterations that are not captured by conventional disease activity scores.