Oral farnesol treatment of gastrointestinal inflammation models highlights the need for developing novel delivery methods 2257415

Abstract

Abstract Introduction Farnesol (FOL) is a sesquiterpene alcohol produced as an intermediate of the mevalonate pathway. FOL has immunoregulatory effects in experimental models of cancer, neuroinflammation, and gastrointestinal (GI) inflammation. In addition, FOL contributes to microbiome homeostasis, suggesting FOL’s therapeutic effects in GI inflammation have a multifaceted approach. FOL is highly hydrophobic, which hinders its delivery. Corn oil (CO) is a commonly used vehicle in disease studies; however, CO, and other oil types, is shown to have confounding effects on disease models and microbiome modulation. We propose to test the impact of CO on FOL’s effectiveness as a therapeutic when administered as a delivery vehicle in both in vitro and in vivo GI inflammation models. We also provide preliminary data for a novel liposome preparation to improve efficacy of oral FOL delivery. Methods Experimental colitis was induced with one dose of TNBS, and FOL or CO control were orally delivered daily. Weights were collected daily and fecal samples were collected for microbiome analysis. Naive fecal samples were cultured in varying conditions to study effects of FOL in CO and CO alone. Model intestinal cell co-cultures were utilized to study intestinal barrier and immune responses to FOL treatment. FOL and control liposomes were prepared via a modified thin-film method. Results FOL and CO alone both have significant impact on TNBS-associated pathology/mortality. The microbiome composition from in vivo and in vitro studies show FOL and CO have unique modulatory activity on the microbiome, highlighting a need for less influential delivery methods. We designed a preliminary FOL liposome that provides a more targeted approach for FOL delivery without the use of CO. Conclusion Our study highlights the need for optimized delivery methods due to the impact CO has on immunological and microbial studies. We propose a liposome-based therapeutic approach to better characterize FOL as a natural therapeutic approach in future studies. Funding Source National Institutes of Health #1R15AI191202-01 Idaho INBRE Technology Access Grant #P20GM103408 Topic Categories Mucosal and Regional Immunology (MUC)