Ryan Fansler

The human gastrointestinal tract is home to trillions of microbes collectively termed the gut microbiota. At homeostasis, the gut microbial community provides pivotal functions to human health. However, perturbations such as intestinal inflammation can drive the microbiota towards a perturbed state termed dysbiosis. As dysbiotic microbiota causes and exacerbates diseases in susceptible hosts, factors that prevents the gut microbiota from entering a dysbiotic state or facilitate the reversion to the original equilibrium, such as microbial resilience, are fundamental in maintaining host health. Despite being considered essential for maintaining the stable structure and function of the human microbiome over time, little is known about the mechanisms by which the microbiota remains resilient in the face of perturbations such as intestinal inflammation.

Iron is essential to many biological redox reactions. During episodes of intestinal inflammation, the host immune system sequesters free iron during as a defense against microbial invaders. To survive iron limitation, gut commensals must exert tight control of iron uptake and utilization. However, little is known about how commensals maintain iron homeostasis in the inflamed intestine. My project focuses on elucidating the role of iron homeostasis in the resilience of commensal model organism Bacteroides thetaiotaomicron (B. theta) in the context of gut inflammation. Specifically, I will 1) determine whether iron-sparing response contributes to B. theta fitness in the inflamed intestine and 2) define the mechanisms by which small RNAs regulate iron prioritization in Bacteroides thetaiotaomicron in vitro and in vivo. A better understanding of iron regulation’s role in microbiota resilience may contribute to the rational design of therapeutic interventions for a dysbiotic gut.

Mentor: Wenhan Zhu, Ph.D.