The aim of this study was to determine the effects of wheat germ polysaccharides (WGPs), which are indigestible carbohydrate fibers, on mice in early life, and the changes leading to long-lasting consequences. We determined the influences of early life ceftriaxone and WGP treatment on intestinal microbiota and immunity both in newborn and adulthood mice. The results showed that ceftriaxone significantly altered the intestinal microbiota, short-chain fatty acids' (SCFAs) metabolism, organ index, and serum OVA-specific IgE levels in newborn mice. Comparing adulthood mice to ceftriaxone-treated mice, the diversity and composition of intestinal microbiota were significantly improved after WGP treatment. In addition, the levels of OVA-specific IgE in the WGP-treated mice were significantly decreased, and the expression of cytokines (IL-2, IL-4, IL-6, IFN-γ, and TNF-α) were obviously increased. Therefore, we speculate that the mechanism of action of the indigestible carbohydrate fibers of WGPs is through maintaining immune homeostasis in newborns, which may partly last into adulthood. More importantly, this may be closely related to alterations in the intestinal microbiota.