Characterizing bioelectrical signaling between the gut microbiota and the host

PROJECT SUMMARY/ABSTRACT Cellular communication is a complex interplay of biochemical, biophysical, and bioelectrical signaling. Beyond well-known neuronal action potentials, various mechanisms of bioelectricity play a pivotal role in most host processes. Its significance extends to microbial realms, facilitating communication within and between bacterial species in environmental biofilms. Our preliminary studies, along with others, indicate the potential for interkingdom bioelectric interactions, particularly between gut microbes and their mammalian hosts. Yet, the bioelectrical aspect of this interface remains largely unexplored, necessitating innovative tools and dedicated research. While traditional gut microbiota research has identified correlations between microbial shifts and diseases, our laboratory aims to delve deeper, uncovering the precise mechanisms of gut-host communication at the cellular and molecular levels. We plan to harness cutting-edge advancements in gut microbial research, unique bacterial filament characterization, and pioneering bioelectrical tools to modulate bacterial and host signals. Intriguingly, certain soil bacteria can thrive on and release electrons directly, bypassing conventional energy sources. They utilize extracellular electron transfer mechanisms, such as conductive nanowires, to move electrons into or out of their cells. The role of this mechanism in the competitive landscape of the intestinal environment remains uncharted. We postulate that bacteria in the mouse gut utilize these conductive nanowires for successful colonization and to exchange electrical signals with the intestinal barrier, which in turn influences broader bioelectric signaling in the host. We anticipate that bacteria with nanowires will have a competitive edge over nanowire-deficient mutants. Our proposal's primary objectives are to characterize the production and functional implications of these conductive nanowires in human gut microbes. We aim to explore the intricate, bidirectional interactions between the gut microbe and its host. We believe these interactions have far-reaching implications, influencing not just the gut but also the immune, cardiovascular, and nervous systems. Deciphering these interactions could pave the way for innovative bioelectrical therapeutic strategies for both intestinal and systemic conditions.