Carbon monoxide-producing probiotic Escherichia coli attenuates HSV-1 skin disease.

Persistent infections and inflammatory diseases remain major health challenges due to their prevalence and limited prophylactic and therapeutic options. Heme oxygenases (HOs) degrade heme into bioactive molecules, including carbon monoxide (CO), a traditionally toxic gas yet naturally produced in mammals to regulate inflammation. Here, we investigated whether bacterial CO production via bacterial heme oxygenase ChuS, present in commensal Escherichia coli, could confer prophylactic effects against HSV-1 skin infection. Oral administration of E. coli Nissle 1917 (EcN) increased serum carboxyhemoglobin in a ChuS-dependent manner. Moreover, isolated commensal E. coli strains carrying chuS, but lacking the genotoxin colibactin, enhanced CO levels and reduced HSV-1 severity. Combined administration of these strains elicited a trend toward reduced disease severity and a significant reduction in viral load compared to controls. These findings identify ChuS as a microbial driver of CO-mediated anti-inflammation and highlight probiotic E. coli as a safe, natural platform for CO delivery.