Dibakoane, SRMhlongo, GMoonsamy, GhaneshreeWokadala, OC , SR MhlongoMnisi, CMMlambo, V2026-02-102026-02-102025-050032-57911525-3171https://doi.org/10.1016/j.psj.2025.105049http://hdl.handle.net/10204/14668Despite their growing popularity as alternatives to antibiotic growth promoters (AGPs), the individual effects of nucleotides and probiotics on poultry gut functionality remain poorly understood. In addition, inconsistent outcomes are quite common in studies where these two additives have been used separately to modify gut function and related parameters in birds. These inconsistencies, which have limited the potential of probiotics and nucleotides as AGP replacements, stem from various factors and need to be addressed. Combining probiotics and nucleotides could potentially enhance their effectiveness and lead to more consistent outcomes in layer chickens. Since their mechanisms of action complement each other, some level of synergy is expected when used together. Both additives have been shown to support gut health, boost immune function, and improve performance in chickens when used individually. However, no studies have investigated the possible synergistic effects of nucleotides and probiotics in poultry. This review makes the case for combined use of probiotics and nucleotides in layer chickens by providing phenomenological and mechanistic insights into hypothetical synergistic effects. This paper highlights the need for AGP alternatives and reviews studies on the effects and mechanisms of probiotics and nucleotides in layer chickens when used individually. We then propose potential mechanisms for their synergistic effects on gut health, performance, and egg quality based on logical deductions from observed biological responses. These proposed mechanisms are hypothetical and require experimental validation. Finally, the review explores how this synergy could lead to more consistent outcomes and enhance the feasibility of AGP-free egg production.FulltextenGut functionProbioticEgg qualityDietary nucleotideSynergismArticlen/a