Dr. Baumler is a pioneer studying microbial physiology in its natural context of a host-associated microbial community. An overarching theme of his research is that the host plays a key role in shaping its gut microbiota to be beneficial. His work shows that the host maintains gut homeostasis by epithelial hypoxia in the colon, thereby limiting the availability of oxygen and other electron acceptors in the large intestine to obtain microbial fermentation products from fiber. Increased epithelial oxygenation in the colon disrupts this host control mechanism, resulting in a shift in the microbial community from obligate to facultative anaerobes. This dysbiotic shift in the gut microbiota is observed during infection with enteric pathogens, such as Salmonella and Citrobacter, during chemically-induced colitis, in mouse models of genetically-induced colitis or after antibiotic treatment.

Importantly, Dr. Baumler’s work shows that an increased availability of respiratory electron acceptors is a shared driver of gut dysbiosis in each of these settings.  Studies on the underlying mechanism reveals that regulatory T cells and epithelial PPAR-gamma signaling act in concert to maintain epithelial hypoxia through a virtuous cycle that maintains gut homeostasis. By providing a mechanistic explanation for the elusive concept of gut homeostasis, these insights provide a novel lynchpin for strategies to remediate dysbiosis in a broad spectrum of human diseases by harnessing epithelial control mechanisms for therapeutic means.