Our Research
Research in the Lund Lab generally focuses on how resident microbes in the gut, collectively known as the microbiota, interact with the host epithelium to promote homeostasis and how alterations in these interactions contribute to pathological states like inflammatory bowel disease.
The gut epithelium forms a critical barrier that physically separates the microbiota from the underlying host tissue. In the absence of an intact epithelium, microbes may invade host tissues and trigger an inflammatory response. While gut homeostasis depends on this physical separation of the microbiota and host, it also depends on symbiotic interactions between them. Such interactions often occur through the small molecule metabolites produced by the microbiota, which affect processes like cell differentiation, nutrient absorption, epithelial barrier function, tumorigenesis, and inflammation. For instance, fermentation of dietary fiber by the microbiota generates butyrate and other short-chain fatty acids, which are thought to be the main sources of energy for epithelial cells via beta oxidation.
Now that sequencing approaches have revealed the composition of the microbiota and its genetic potential for small molecule production, complementary approaches to assess its functional output are needed to deepen our understanding of host-microbiota interactions and their role in health and disease. As a versatile platform for the high-throughput analysis of small molecules and proteins in both hypothesis-driven and hypothesis-generating research, mass spectrometry is ideally suited to accomplish this goal. Thus, a major endeavor in the Lund Lab is to apply mass spectrometry and other high-throughput approaches to determine which components of the microbial metabolome have a functional effect on host cells and then elucidate the pathways responsible for these effects. We are especially interested in how small molecules produced by microbes can serve as metabolic precursors and receptor ligands, thereby modulating energy balance and gene expression in host cells. Underscoring the clinical relevance of our work on energy homeostasis in the gut, ulcerative colitis has been associated with deficient beta oxidation in epithelial cells. Ultimately, we hope that our research will advance insight into the causes of inflammatory bowel disease and contribute to the development of new therapeutics.
