Project description:The gut microbiota promotes immune system development in early life, but the interactions between the gut metabolome and immune cells in the neonatal gut remains largely undefined. Here, we demonstrate that the neonatal gut is uniquely enriched with neurotransmitters, including serotonin; specific gut bacteria produce serotonin directly while downregulating monoamine oxidase A to limit serotonin breakdown. Serotonin directly signals to T cells to increase intracellular indole-3-acetaldehdye to inhibit mTOR activation and thereby promotes the differentiation of regulatory T cells, both ex vivo and in vivo in the neonatal intestine. Oral gavage of serotonin into neonatal mice leads to long-term T cell-mediated antigen-specific immune tolerance towards both dietary antigens and commensal bacteria. Together, our study has uncovered an important role for unique gut bacteria to increase serotonin availability in the neonatal gut and a novel function of gut serotonin to shape T cell response to dietary antigens and commensal bacteria to promote immune tolerance in early life.
Project description:The gut microbiota promotes immune system development in early life, but the interactions between the gut metabolome and immune cells in the neonatal gut remains largely undefined. Here, we demonstrate that the neonatal gut is uniquely enriched with neurotransmitters, including serotonin; specific gut bacteria produce serotonin directly while downregulating monoamine oxidase A to limit serotonin breakdown. Serotonin directly signals to T cells to increase intracellular indole-3-acetaldehdye to inhibit mTOR activation and thereby promotes the differentiation of regulatory T cells, both ex vivo and in vivo in the neonatal intestine. Oral gavage of serotonin into neonatal mice leads to long-term T cell-mediated antigen-specific immune tolerance towards both dietary antigens and commensal bacteria. Together, our study has uncovered an important role for unique gut bacteria to increase serotonin availability in the neonatal gut and a novel function of gut serotonin to shape T cell response to dietary antigens and commensal bacteria to promote immune tolerance in early life.
Project description:The gut microbiota promotes immune system development in early life, but the interactions between the gut metabolome and immune cells in the neonatal gut remains largely undefined. Here, we demonstrate that the neonatal gut is uniquely enriched with neurotransmitters, including serotonin; specific gut bacteria produce serotonin directly while downregulating monoamine oxidase A to limit serotonin breakdown. Serotonin directly signals to T cells to increase intracellular indole-3-acetaldehdye to inhibit mTOR activation and thereby promotes the differentiation of regulatory T cells, both ex vivo and in vivo in the neonatal intestine. Oral gavage of serotonin into neonatal mice leads to long-term T cell-mediated antigen-specific immune tolerance towards both dietary antigens and commensal bacteria. Together, our study has uncovered an important role for unique gut bacteria to increase serotonin availability in the neonatal gut and a novel function of gut serotonin to shape T cell response to dietary antigens and commensal bacteria to promote immune tolerance in early life.
Project description:D-galactose orally intake ameliorate DNCB-induced atopic dermatitis by modulating microbiota composition and quorum sensing. The increased abundance of bacteroidetes and decreased abundance of firmicutes was confirmed. By D-galactose treatment, Bacteroides population was increased and prevotella, ruminococcus was decreased which is related to atopic dermatitis.
Project description:The microbiota of the mouth disperses into the lungs and both compartments share similar phyla. Considering the importance of the microbiota in the maturation of the immunity and physiology during the first days of life, we hypothesized that primo-colonizing bacteria of the oral cavity may induce immune responses in bronchial epithelial cells. Herein, we have isolated and characterized 57 strains of the buccal cavity of two human new-borns. These strains belong to Streptococcus, Staphylococcus, Enterococcus, Rothia and Pantoea genera; Streptococcus being the most represented. The strains were co-incubated with a bronchial epithelial cell line (BEAS-2B) and we established their impact on a panel of cytokines/chemokines and global changes in gene expression. The Staphylococcus strains, which appeared soon after birth, induced a high production of IL-8, suggesting they can trigger inflammation, whereas the Streptococcus strains were less associated with inflammation pathways. The genera Streptococcus, Enterococcus and Pantoea induced differential profiles of cytokine/chemokine/growth factor and set of genes associated with maturation of morphology. Altogether, our results demonstrate that the micro-organisms, primo-colonizing the oral cavity, impact immunity and morphology of the lung epithelial cells, with specific effects depending on the phylogeny of the strains.