Sarah Maddux (Mentor: Michael Silverman, MD, PhD)

“The commensal microbe Akkermansia muciniphila induces peripheral Tregs in early life and enhances humoral responses to other commensals”

Sarah Maddux, Jamal Green, Jean-Bernard Lubin, Tereza Duranova and Michael Silverman

Variations in commensal microbiome composition are associated with immune disfunction and individual microbes have been shown to modulate immune development and autoimmunity. The mucus-degrading microbe Akkermansia muciniphila is a common human commensal that is correlated with better outcomes for conditions ranging from autoimmune diabetes to cancer immunotherapy; it is an immunostimulatory microbe that strengthens the intestinal epithelial barrier and is capable of inducing antigen-specific T cell and antibody responses. However, little is known about the mechanisms by which A. muciniphila influences host immunity and barrier function. My work shows that induction of peripheral Tregs (pTregs) is age restricted; early life exposure to the microbe is necessary for pTreg induction. Using a defined murine pediatric microbial community our lab developed called Pedscom, I have found that in addition to stimulating a strong systemic antibody response to itself, A. muciniphila enhances systemic antibody responses to other commensal microbes. Collectively, this data indicates that A. muciniphila alters immune development and responses to the microbiota in early life in a potentially tolerogenic manner.