Asthma, obesity, and irrational use of antibiotics early in a life can be considered to be the three epidemics of modern times, which encourage one another and whose base is the loss of bioavailability. Disruption of the intestinal microbiome early in the life is the basis for the development of metabolic diseases, allergic immunological diseases, and high mortality rate due to infection with resistant strains of bacteria. During the irrational use of penicillin and macrolides postnatally, the composition of the intestinal microbiota and its functions change 12-24 months after the antibiotics treatment, the settlement of advantage intestinal flora with probiotic microorganisms is delayed, the maturation of the intestinal mucosa is compromised. Respiratory and systemic inflammation is strongly influenced by the rich adipocyte metabolism so that the treatment of these children is complex, and their asthma often remains only partially controlled. The phenotype "obese asthma" is characterized by a steroid and bronchodilator resistance. Therapeutic solution could be the body weight reducing, vitamin D3 substitution, and antileukotriene application. The prophylactic therapy of this asthma, using macrolides for a long time, should be supported, mandatory, with the substitution of probiotic/synbiotic during, and at least 6-9 months after discontinuation of therapy with macrolide.