Karst Laboratory
University of Florida, Dept. of Molecular Genetics and Microbiology
Research
Viruses & Neonatal Immunity
Maternal signals help determine how effectively newborns respond to viral infection.
Early life is a period of heightened susceptibility to viral disease, yet the factors that establish neonatal antiviral competence remain poorly understood. Our work identified maternal and microbial bile acids as previously unrecognized regulators of antiviral immunity during this critical window.
Using neonatal murine norovirus, we discovered that microbiota-derived bile acids protect against severe disease by activating a TGR5-dependent type I interferon response in the intestine. Ongoing studies are defining the TGR5-expressing cell populations required for this protective response.
We are also extending this work to systemic neonatal viruses, where our emerging studies reveal that milk bile acids regulate susceptibility to infection through a distinct, TGR5-independent mechanism. Ultimately, we aim to translate these discoveries into strategies that harness maternal and microbial metabolites to enhance antiviral protection during early life.
Maternal & Microbial Metabolites
Milk provides a route for transmitting maternal and microbial signals to the developing infant.
We discovered that bile acids are transferred through milk and that the composition of this pool is shaped by both the maternal microbiota and diet. These findings reveal milk as a previously underappreciated route for delivering host- and microbiota-derived metabolites to the neonate during a critical period of development.
Our ongoing work asks how this maternal–infant metabolic axis is established and whether it can be manipulated to improve infant health. We are investigating how specific bile acids are selected for transport into milk and testing dietary and live bacterial interventions designed to reshape the maternal bile acid pool.
We are also addressing an important unanswered question: do milk bile acids help establish the neonatal gut microbiome? Although bile acids are known to shape microbial communities, the relative contributions of maternally derived and neonatally produced bile acids remain unknown.
Developmental Programming
Signals received during a brief early-life window have lasting consequences for tissue development and metabolic health.
Our work revealed that milk bile acids regulate neonatal growth through TGR5-dependent signaling and the IGF-1 axis, identifying a mechanism through which the maternal environment can influence growth during a critical developmental window.
Remarkably, the consequences of milk bile acid exposure persist long after nursing ends. Experimentally altering bile acid availability during lactation produces lasting differences in adipose tissue mass and architecture, body weight, and insulin sensitivity in adult offspring. These findings suggest that milk bile acids function as developmental signals that help establish long-term metabolic physiology.
Our ongoing studies are defining how transient bile acid signaling during early life programs adipose tissue development, with a particular focus on adipocyte progenitors, adipogenesis, and lipid storage. Ultimately, we aim to understand how maternal and early-life environments establish susceptibility or resilience to metabolic disease later in life.