We study human health and disease through the trillions of bacteria that live in our gut. These bacteria not only make up more than half the cellular composition of the human body, they also generate a vast array of byproducts that serve as currencies for exchange of information between our body and the outside world.
Of all the external factors that can influence the trading between bacteria and human cells, the amino acids, sugars, fatty acids, and fibers that make up our diet are the most ubiquitous and potent. The emergent patterns of microbial growth and productivity reveal both novel, and long-evolved relationships between host and microbe that can be leveraged for health.
Our goal is to define the mechanistic underpinnings of diet’s extraordinary impact on the gut microbiome and translate these findings into prospective human studies in patients suffering from inflammatory and metabolic diseases in order to add a powerful dimension to the diagnosis and treatment of inflammatory bowel diseases (IBDs), diabetes, and cancer.
Metabolic Pathways of Sulfur-Reducing Bacteria (SRB) and Functional Contribution to Gut Inflammation
Bilophila wadsworthia is a unique Deltaproteobacteria and SRB first identified in human intestinal abscesses. Our early work (Devkota et al., Nature 2012) defined the first mechanism by which excess dietary saturated fat consumption can lead to colitis by promoting B. wadsworthia growth in the gut through a bile-acid linked mechanism. We are continuing to define the role of B. wadsworthia in gut inflammatory diseases as well as related members of SRB's.
New Microbiology: Bacterial Cultivation and Tool Development
We are actively sourcing novel culture ingredients and growth platforms to improve in vitro isolation of bacteria. These tools can be leveraged to efficiently screen microbial metabolic pathways, create defined consortia, and aid in gnotobiotic mouse studies. In collaboration with industry partners we are testing and validating new tools and applications in order to bring microbial sciences up to speed with current sequencing technologies.
Dietary Drivers of Microbial Function- Overconsumption, Starvation, and Everything in Between
We design custom diets and feeding protocols addressing microbiome-based questions across the spectrum of dietary pathologies such as overconsumption in chronic inflammatory and metabolic diseases, and starvation and malnutrition, as well as lifestyle choices such as vegan vs. omnivore. In vivo studies combined with in vitro screening of responsive microbes and their metabolites allows us to develop robust comparative dietary studies for testing prospectively in patients.
Our human studies leverage the efficient clinician-scientist interface at Cedars-Sinai. We work closely with the Inflammatory Bowel Disease Center, Nutrition Service, IBIRI biobank, and colorectal surgeons (Crohn’s and colitis studies); Samuel Oschin Cancer Center (GI cancer studies), and Diabetes and Obesity Research Institute (obesity and diabetes studies) to understand the inflammatory and/or metabolic pathologies that underlie these disease and determine points of prevention or intervention for dietary and microbiome based therapies.
Devkota S. Prescription drugs obscure microbiome analyses. Science. 351:6272:352-3. (2016) -- (View Publication)
Broussard JL, Devkota S. The changing microbial landscape of Western Society: Diet, dwellings and disconcordance. Molecular Metabolism. 5(9):737-42. (2016) -- (View Publication)
Devkota S, Wang Y, Musch M, Leone V, Fehlner-Peach H, Nadimpalli A, Antonopoulos D, Jabri B, Chang EB. Dietary fat-induced taurocholic acid production promotes pathobiont expansion and colitis in IL-10-/- mice. Nature. 487(7405):104-108. (2012) -- (View Publication)