Probiotics and Antibiotics: From Empirical Practice to a Biological Rationale for Targeted Choice During Antibiotic Therapy

Antibiotic therapy represents one of the strongest ecological perturbations of the human gut microbiota, inducing rapid and often prolonged alterations in community structure, metabolic activity, and functional resilience. While the use of probiotics to mitigate antibiotic-associated dysbiosis is widely adopted in clinical practice, probiotic selection is still largely empirical and insufficiently grounded in biological compatibility with specific antibiotic pressures. In this conceptual review, antibiotics are reframed not merely as antimicrobial agents, but as ecological forces that shape microbial survival, quiescence, and recolonization dynamics. We propose a biologically informed framework that distinguishes genetic antibiotic resistance from functional or ecological insensitivity, highlighting how microbial traits, such as the absence or inaccessibility of the antibiotic target, metabolic state, sporulation, and cellular architecture, influence the persistence of probiotics during antibiotic exposure. By integrating the mechanisms of action of antibiotics with key physiological and structural features of probiotic microorganisms, we develop a conceptual framework aimed at rationalizing the compatibility of probiotics and antibiotics. This framework does not imply clinical efficacy but provides an interpretative tool to guide hypothesis generation, experimental validation, and the design of future targeted probiotic strategies. A more ecologically grounded approach to probiotic selection may ultimately improve microbiota support during antibiotic therapy and advance personalized microbiome modulation.