Uridine and pyruvate supplementation is associated with Th1 polarization during mitotoxic antibiotic therapy.

Antibiotics with off-target mitochondrial toxicity can impair host immunity, yet their impact on human adaptive immunity in vivo remains unclear. Because T cell activation and differentiation depend on mitochondrial metabolism, antibiotic-induced mitochondrial stress may alter T helper cell function. We investigated whether uridine and pyruvate (UP) supplementation modulates immune responses in patients receiving mitotoxic antibiotics. In a pilot observational study, 67 patients undergoing prophylactic antibiotic therapy received either antibiotics alone or antibiotics plus daily UP supplementation. Antibiotic exposure increased circulating growth differentiation factor-15 (GDF15), indicating mitochondrial stress, and altered T cell response. UP supplementation was associated with immune features consistent with preserved inflammatory competence, including a trend toward Th1 polarization. These findings suggest that mitotoxic antibiotics can influence human T cell programs and support the hypothesis that UP supplementation may preserve pro-inflammatory T cell responses during antibiotic therapy, representing a potential metabolic strategy to mitigate antibiotic-induced immunotoxicity.