Protective response against mycobacteriosis by probiotic bacteria with high alpha‐Gal content involves mechanisms such as the modification of gut microbiota composition, B‐cell maturation, anti‐alpha‐Gal IgM antibodies‐mediated control of mycobacteria, induced innate immune responses, beneficial effects on nutrient metabolism and reduced oxidative stress. This evidence concerns the gene CD40LG and mycobacterial infectious disease.