Type-2 Diabetes Mellitus (T2DM) is related to cardiac arrhythmias. The stellate ganglion (SG), part of the sympathetic nervous system, regulates heart function. Within the SG, satellite glial cells (SGCs) have gap junction channels (Cx43). Increased Cx43 permeability induces SGC depolarization and activates the PKC-MAPK14-ADAM17 signaling pathway, releasing some endogenous factors that stimulate nearby cardiac postganglionic sympathetic neurons (CPSN). This study investigated the activation of the PKC-MAPK14-ADAM17 signaling pathway in T2DM SGs and SGCs as a novel mechanism of sympathetic overactivation. A total of 56 Sprague-Dawley rats were randomly assigned to sham and T2DM groups, and T2DM was induced using a high-fat diet combined with low-dose streptozotocin. Real-time RT-PCR, Western blot, and ELISA quantified mRNA/protein expression and enzymatic activity. The patch clamp technique assessed neuronal voltage-gated Ca²⁺ currents and action potentials, while electrophysiological recording measured cardiac sympathetic nerve activity (CSNA). T2DM rats exhibited marked upregulation of MAPK14, PKC-α, and ADAM17 mRNA/protein in the SG, alongside elevated enzymatic activities of PKC and ADAM17. T2DM also increased Ca²⁺ currents and neuronal excitability in the CPSN and induced the elevation of the CSNA. Upregulated PKC-MAPK-ADAM17 signaling in the SG might contribute to cardiac sympathetic overactivation in T2DM rats by enhancing the cell excitability of the CPSN.

Background: The gut–skin axis links intestinal microbial activity with inflammatory skin disease, yet findings across atopic dermatitis, acne vulgaris, and psoriasis remain inconsistent. This review examines how disease biology and host context shape microbiome‐related effects and responses to probiotics. Materials and Methods: Published clinical and experimental evidence on gut microbiota, immune and metabolic signaling, barrier dysfunction, inter‐organ communication, and probiotic interventions was narratively reviewed across atopic dermatitis, acne vulgaris, and psoriasis. Results: Microbiome‐related mechanisms differ by disease. In atopic dermatitis, they intersect with barrier dysfunction and altered immune regulation. In acne vulgaris, metabolic, hormonal, dietary, and neuroendocrine factors modify their effects. In psoriasis, gut dysbiosis occurs within a broader setting of systemic immune activation. Probiotic outcomes are similarly variable and depend on strain, host characteristics, disease context, and study design. Discussion: Gut–skin communication is better interpreted as part of an interconnected physiological network rather than a uniform linear pathway. Disease‐specific evaluation of microbiome changes and probiotic interventions may help explain conflicting findings and guide more targeted future studies.