Influence of gut microbiota on immunological maturation in infancy

Maturation and function of the immune system is highly influenced by the establishment of the microbiota in the gut, which in turn, particularly in infancy, is influenced by factors such as maternal microbiota and the environment, including diet. Studies have shown that although lymph nodes are able to elicit mixed Th1/Th2 responses, Th2 responses dominate in the spleen in the neonatal mouse.

In this study, we compared phenotypic markers present on mesenteric lymph nodes (mLNs) and spleens from 3 weeks old mice, to levels found in adult mice. We found that mLNs displayed levels of CD4+ and CD8+ T-cells as well as NK-cells similar to those found in adult mice, while splenocytes expressed severely reduced levels of these markers and were impaired in their ability to proliferate in response to anti-CD3/anti-CD28.

To further characterize the development of immunological maturation in spleens from young mice, female mice were administered different probiotics during pregnancy and lactation and their offspring sacrificed at the age of 3 weeks. Interestingly, intake of Bb. longum Q46 or E. coli Nissle 1917 resulted in reduced levels of CD4, CD8 and CD49b on the cell surface of splenocytes as well as impaired ex vivo proliferative abilities of T lymphocytes as measured by 3H-TdR incorporation.

Furthermore, Bb. longum Q46 and E. coli Nissle 1917 promoted a non-Th2 cytokine profile in splenocytes from offspring, and reduced cellular activation during ex vivo polyclonal stimulation. These results show that, although the maturation status of spleens, as representatives for the systemic immune system in mice aged 3 weeks, is quite low compared to mLNs, the maturation status and effector-function of spleens can be altered by administering probiotics during pregnancy.