Recent studies have demonstrated that antibiotics/or probiotics administration in early life play key roles on modulating intestinal microbiota and the alterations might cause long-lasting consequences both physiologically and immunologically. We investigated the effects of early life ceftriaxone, vancomycin and Bifidobacterium bifidum TMC3115 (TMC3115) treatment on intestinal microbiota and immunity both in neonates and adults even after termination of antibiotics exposure. We found that ceftriaxone and vancomycin, but not TMC3115, significantly altered the intestinal microbiota, serum total IgE level, and the morphology and function of the intestinal epithelium in the neonatal mice. In the adult stages, the diversity and composition of the intestinal microbiota were significantly different in the antibiotic-treated mice, and ceftriaxone-treated mice exhibited significantly higher serum total IgE and OVA-specific IgE levels. TMC3115 significantly mitigated the alteration of intestinal microbiota caused by ceftriaxone not vancomycin. Antibiotics and TMC3115 can differently modulate intestinal microbiota and SCFAs metabolism, affecting the development and function of the immunity and intestinal epithelium to different degrees in neonatal mice. Neonatal ceftriaxone-induced abnormal intestinal microbiota, immunity and epithelium could last to adulthood partly, which might be associated with the enhancement of host susceptibility to IgE-mediated allergies and related immune responses, TMC3115 may protect against the side effects of antibiotic treatment, at least partly.