Skin Microbiota: Mediator of Interactions Between Metabolic Disorders and Cutaneous Health and Disease

Abstract

Metabolic disorders, including type 2 diabetes mellitus (T2DM), obesity, and metabolic syndrome, are systemic conditions that profoundly impact the skin microbiota, a dynamic community of bacteria, fungi, viruses, and mites essential for cutaneous health. Dysbiosis caused by metabolic dysfunction contributes to skin barrier disruption, immune dysregulation, and increased susceptibility to inflammatory skin diseases, including psoriasis, atopic dermatitis, and acne. For instance, hyperglycemia in T2DM leads to the formation of advanced glycation end products (AGEs), which bind to the receptor for AGEs (RAGE) on keratinocytes and immune cells, promoting oxidative stress and inflammation while facilitating Staphylococcus aureus colonization in atopic dermatitis. Similarly, obesity-induced dysregulation of sebaceous lipid composition increases saturated fatty acids, favoring pathogenic strains of Cutibacterium acnes, which produce inflammatory metabolites that exacerbate acne. Advances in metabolomics and microbiome sequencing have unveiled critical biomarkers, such as short-chain fatty acids and microbial signatures, predictive of therapeutic outcomes. For example, elevated butyrate levels in psoriasis have been associated with reduced Th17-mediated inflammation, while the presence of specific Lactobacillus strains has shown potential to modulate immune tolerance in atopic dermatitis. Furthermore, machine learning models are increasingly used to integrate multi-omics data, enabling personalized interventions. Emerging therapies, such as probiotics and postbiotics, aim to restore microbial diversity, while phage therapy selectively targets pathogenic bacteria like Staphylococcus aureus without disrupting beneficial flora. Clinical trials have demonstrated significant reductions in inflammatory lesions and improved quality-of-life metrics in patients receiving these microbiota-targeted treatments. This review synthesizes current evidence on the bidirectional interplay between metabolic disorders and skin microbiota, highlighting therapeutic implications and future directions. By addressing systemic metabolic dysfunction and microbiota-mediated pathways, precision strategies are paving the way for improved patient outcomes in dermatologic care.

Keywords: acne; atopic dermatitis; biomarkers; metabolic disorders; precision dermatology; psoriasis; skin microbiota.

Figure 1

Interconnected pathways linking metabolic disorders to skin microbiome dysbiosis and cutaneous disease. Metabolic disorders influence skin health and the microbiome through interconnected mechanisms. Chronic low-grade inflammation, or meta-inflammation, driven by pro-inflammatory cytokines such as TNF-α, IL-6, and IL-1β, disrupts keratinocyte differentiation, weakens the epidermal barrier, and alters AMP production, increasing susceptibility to infections and dysbiosis. Immune dysregulation plays a significant role, as adipokines like leptin promote Th1/Th17 polarization, while reduced adiponectin removes anti-inflammatory control, intensifying immune activation and microbial imbalances. Neurovascular dysregulation, a notable mechanism in rosacea, is driven by the increased activation of pathways such as TRPV1 channels and exacerbates skin sensitivity and dysbiosis. Microvascular dysfunction and reduced capillary perfusion create hypoxic conditions that favor anaerobic or facultative anaerobic microbes, altering microbial ecology. Dysregulated lipid metabolism, particularly altered sebaceous gland activity in insulin resistance, leads to changes in sebum composition, such as increased saturated fatty acids, which promote the colonization of pathogenic microbes and disrupt the balance of commensal microbes. Systemic nutritional and metabolic influences, including hyperglycemia and dyslipidemia, provide substrates for microbial growth, destabilizing skin homeostasis. Oxidative stress and lipid peroxidation further damage keratinocytes and lipids, compromising skin integrity and promoting microbial overgrowth. Sebaceous gland hyperactivity, induced by hyperinsulinemia and IGF-1, stimulates excessive lipid production, creating a nutrient-rich environment for opportunistic microbes. Cytokines and oxidative stress reduce the expression of barrier proteins like filaggrin and involucrin, increasing transepidermal water loss and weakening physical defenses against microbial invasion. AGEs, formed under hyperglycemic conditions, bind to their receptor RAGE, triggering NF-κB-mediated inflammation and oxidative stress. This process impairs skin barrier proteins, disrupts collagen cross-linking, and affects keratinocyte function. These mechanisms collectively illustrate how metabolic disorders create both systemic and localized environments conducive to skin dysbiosis, inflammation, and disease, underscoring the need for integrated therapeutic strategies targeting metabolic dysfunction and skin health. Systemic effects are marked in blue, while localized effects are marked in orange.

Figure 2

Flowchart of the complex interactions between AGE-RAGE pathway and the skin. Abbreviations. AGEs (Advanced Glycation End Products); AMP (Antimicrobial Peptides); NF-κB (Nuclear Factor Kappa-Light-Chain-Enhancer of Activated B cells); RAGE (Receptor for Advanced Glycation End Products); ROS (Reactive Oxygen Species); TEWL (Transepidermal Water Loss); ↑ (increased); ↓ (decreased).