The interplay between gut microbiota and the immune system has a pivotal role in the maintenance of bone health. Short-chain fatty acids (SCFAs) such as butyrate produced by gut microbiota have emerged as key regulatory participants in shaping the immune system. Butyrate has been observed to have local and systemic effects including inducing the differentiation of peripheral regulatory T cells (Tregs) in the intestine, blood, and bone marrow. Tregs are the central actors of the negative feedback component of the immune system. The interaction between Tregs and cytotoxic CD8+ T cells suppress the inflammatory status and promote the production of Wnt10b to increase bone formation. However, the therapeutic benefit of butyrate in bone anabolism remains poorly understood. The Ford Versypt Lab is collaborating with Dr. Brenda Smith of the Department of Nutritional Sciences at Oklahoma State University to build a physiologically based pharmacokinetic model connecting butyrate in the gut to bone formation via the immune system.