Abstract
Chronic itch is a debilitating condition characterized by persistent pruritus lasting more than six weeks, significantly impairing quality of life. While the role of the immune system and neural circuits in itch is increasingly understood, the contribution of the skin microbiome, especially in non-atopic itch disorders, remains underexplored. This review synthesizes emerging evidence on how microbial dysbiosis contributes to chronic pruritus through multiple molecular pathways: disruption of skin barrier integrity, modulation of neuroimmune signaling axes, and direct activation of pruriceptors. We highlight recent studies identifying microbiome shifts in prurigo nodularis (PN) and lichen simplex chronicus (LSC), independent of atopic dermatitis (AD). We also evaluate advances in biologics and small-molecule therapeutics, exploring how targeted immune modulation may restore microbial balance and alleviate neuroinflammation. A systems biology approach integrating microbial genomics, neurobiology, and host immunity is critical to unraveling the complex interplay between host and microbes in chronic itch, particularly in understudied non-atopic conditions that disproportionately affect vulnerable populations.