(P19-059-25) Modulation of the Immune Response and Metabolism in Germ-Free Mice by Bifidobacterium animalis subsp. lactis BB-12 in Early Life

Objectives: The establishment of the gut microbiota in early life plays a crucial role in immune development, germ-free animal which possess inherent immune deficiencies, due to the lack of microbial stimulation. This study aims to using germ-free mice to clarify the direct modulation effect of Bifidobacterium animalis subsp. lactis BB-12 on immune development and gut metabolism in early life.

Methods: Germ-free mice were gavaged with BB-12 at 1×10⁸ CFU/ day starting from the second week of birth and continued until weaning at the fourth week, and slaughtered after weaning. The proportion of T cells in spleen and intestinal intraepithelial lymphocytes (iIEL) were analyzed by flow cytometry. The activation and maturation of T cells in thymus and spleen were analyzed to evaluate the immune status of the mice. In addition, tryptophan metabolites and short-chain fatty acids were measured in colon feces to assess the effects of BB-12 intervention on the production of gut metabolites.

Results: Early life administration of BB-12 has a significant impact on the differentiation, maturation, and functional activity of splenic T cells. Compared to the control group, the proportion of central memory CD4+ T cells (CD44+CD62L+) and effector memory CD4+ T cells (CD44+CD62L-) was significantly increased in the BB-12 treated group, while the proportion of naïve CD4+ T cells (CD44-CD62L+) remained unchanged. The metabolomics analysis further supports these findings by showing that B. animalis subsp. lactis intervention greatly increased the production of tryptophan derivatives and acetic acid in the colon of germ-free mice. It is worth noting that the intervention of BB-12 not only enhances the indole pathway mediated by microbes, increasing the content of indole-3-lactic acid (ILA)，indole-3-aldehyde (IAld) in the colon, but also simultaneously enhances the metabolism of tryptophan towards the serotonin pathway and the KYN pathway, increasing the production of key metabolites such as 5-hydroxytryptophan (5-HTP) and pyridine-2-carboxylic acid (PA).

Conclusions: Early life BB-12 administration may activate the host's tryptophan metabolic pathway through the brain-gut-microbe axis, thereby regulating the immune homeostasis of germ-free mice.

Funding Sources: “Nutrition and Care of Maternal & Child Research Fund Project” of Biostime Institute of Nutrition & Care