Response to antihistamines in post-burn pruritus is associated with gut microbiota composition and function: A prospective cohort study with a nested case-control analysis.

Post-burn pruritus (PBP) is a common complication following burn injuries, with substantial interindividual variability in response to antihistamine treatment. While altered gut microbial communities have been observed in patients with histamine intolerance, no studies have examined the relationship between gut microbiota and antihistamine responsiveness in burn patients. Therefore, we hypothesized that the gut microbiome composition differs according to antihistamine responsiveness in patients with PBP. A total of 56 male burn patients categorized into no-pruritus, antihistamine-responsive (HR), and antihistamine-nonresponsive (HNR) groups. Fecal samples were collected at baseline and after 8 weeks of antihistamine treatment. Microbial composition was analyzed using 16S rRNA gene sequencing, and functional prediction was conducted with PICRUSt2. Overall microbial diversity did not differ significantly between groups; however, distinct taxonomic and functional features were identified. The HR group was characterized by enrichment of Sutterella and showed a temporal increase in microbial diversity and Bifidobacterium abundance after 8 weeks of treatment, accompanied by enrichment of redox-related microbial functions. In contrast, the HNR group showed increased Akkermansia and Acidaminococcus with reduced antioxidant defenses and activation of non-histaminergic pruritic pathways. This study is the first to suggest that gut microbiota composition and function are associated with antihistamine responsiveness in patients with PBP. Distinct microbial signatures and functional pathways were identified among non-pruritic individuals, antihistamine responders, and non-responders. Our findings indicate a potential involvement of gut microbes in the pathophysiology of PBP and highlight the possibility of microbiota-targeted therapeutic strategies.