Comparative Effects Of Two Probiotic Formulations On Aerobic Metabolism-Related DNA Methylation

Background Physical activity and nutritional interventions can influnce metabolic adaptation through epigenetic mechanisms, including DNA methylation [1]. In particular, probiotics may modulate host metabolic and inflammatory pathways, potentially affecting the methylation status of gene involved in aerobic metabolism [2]. Understanding whether differend probiotic formulation exert distinct epigenetic effects may help define targeted non -pharmacological strategies to support exercise related adaptation and health [3]. Objective/Aim Evaluate changes in gene-specific DNA methylation related to aerobic metabolism after proviotic supplementation and to compare the effects of two different probiotic formulations: one containing Lactobacillus and Bifidobacterium and one containing only Lactobacillus. Methods Participants underwent a 12-week probiotic supplementation protocol using a formulation containing Lactobacillus and Bifidobacterium, followed, after a break, by a second 12-week supplementation period using a probiotic formulation containing Lactobacillus. Biological samples were collected before and after each intervention phase. Epigenetic analyses were performed to assess global and gene-specific DNA methylation patterns, with a particular focus on genes involved in aerobic energy metabolism. Methylation profiles were compared before and after each supplementation phase and between the two probiotic formulations to identify formulation-related differences. Results Probiotic supplementation has been associated with changes in DNA methylation in genes related to aerobic metabolism. A comparison of the two supplementation phases revealed distinct epigenetic responses, suggesting that the composition of probiotics may differentially influence pathways involved in metabolic efficiency and inflammatory regulation. In particular, the formulation containing Lactobacillus and Bifidobacterium appeared to exert a greater modulatory effect on specific methylation targets compared to the formulation containing only Lactobacillus. Conclusion The two probiotic formulations induced different gene-specific DNA methylation responses in pathways related to aerobic metabolism in the same participants. The combined formulation of Lactobacillus and Bifidobacterium appeared to produce a stronger epigenetic modulation than Lactobacillus alone, supporting a formulation-specific effect of probiotic supplementation on exercise-related metabolic adaptation. References [1] G. Mallett, “The effect of exercise and physical activity on skeletal muscle epigenetics and metabolic adaptations,” 2025. doi: 10.1007/s00421-025-05704-6. [2] A. J. Bittel and Y. W. Chen, “DNA Methylation in the Adaptive Response to Exercise,” 2024. doi: 10.1007/s40279-024-02011-6. [3] H. Mostafavi Abdolmaleky and J. R. Zhou, “Gut Microbiota Dysbiosis, Oxidative Stress, Inflammation, and Epigenetic Alterations in Metabolic Diseases,” 2024. doi: 10.3390/antiox13080985.