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ARS Home » Midwest Area » Lexington, Kentucky » Forage-animal Production Research » Research » Publications at this Location » Publication #427645
Research Project: Increasing Sustainability of Forage Production in Mid-South Agroecosystems

Location: Forage-animal Production Research

Title: The effects of beta-caryophyllene on butyrate utilization and metabolism in caco-2 cells

Author
item SCROGGINS, HANNAH - University Of Kentucky
item KENT-DENNIS, CORAL - Oak Ridge Institute For Science And Education (ORISE)
item MAY, JOHN - University Of Kentucky
item HARMON, DAVID - University Of Kentucky
item Klotz, James

Submitted to: Scientific Reports
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 3/27/2026
Publication Date: 4/1/2026
Citation: Scroggins, H., Kent-Dennis, C., May, J., Harmon, D.L., Klotz, J.L. 2026. The effects of beta-caryophyllene on butyrate utilization and metabolism in caco-2 cells. Scientific Reports. 16. Article 15357. https://doi.org/10.1038/s41598-026-46790-6.
DOI: https://doi.org/10.1038/s41598-026-46790-6

Interpretive Summary: Plants produce natural compounds that can have potential benefits in human and animals. Beta-caryophyllene is a natural compound found in plants like hemp that may have beneficial effects in the intestine. Livestock on high energy diets commonly fed in dairy and feedlot operations can have problems with gut inflammation that causes welfare and production concerns. There has been little research that has looked at the effect of beta-caryophyllene supplementation on the intestine. A cell culture study was used to determine if beta-caryophyllene had potential therapeutic use prior to conducting an animal study. Results demonstrated that beta-caryophyllene can promote the energy metabolism and improve the ability of cells lining the intestine as a barrier against unwanted compounds and organisms. This suggests that beta-caryophyllene has potential to be used in livestock production systems to offset gut inflammation that would improve animal productivity and welfare. This research will be primarily of interest to other researchers looking to improve productivity of livestock, but could lead to eventual adoption by producers as a therapeutic tool.

Technical Abstract: Background: Butyrate is important for regulating energy status and cellular metabolism. ß-caryophyllene (BCP) is a plant compound that may exert potentially beneficial effects on intestinal epithelial cells and modulate nutrient utilization. The goal of this study was to investigate the effects of BCP on butyrate utilization and metabolism in intestinal epithelial cells. Caco-2 cells were used as a model for the intestinal barrier in this study. Results: Treatments were added to triplicate wells per plate (n=4). Treatments included vehicle control (VC), 40 µM BCP, 2 mM butyrate (BUT), and BUT plus BCP (BB). Treatments were added to the apical side of the insert and incubated for 24 and 48 h. Transepithelial electrical resistance (TEER; ohms/cm2) readings and supernatant samples were taken from apical and basolateral sides, butyrate and ß-hydroxybutyrate concentrations were measured. The experiment was repeated using the same treatments; additionally, cells were lysed for gene expression. Compared to VC, the TEER for BUT and BB was greater at 24h (579 vs 878 and 1008 ± 35, respectively; P<0.001). After 48h, all groups returned to baseline, except BB which had a greater TEER (883 ± 35; P < 0.001) compared to other treatments. For BB and BUT groups, more nmol BHB was detected on the basolateral side (31.9 and 22.2 ± 1.3) vs apical (14.0 and 10.4 ± 1.3, respectively; P<0.001) after 24h. After 48h, BHB was also higher on the basolateral side (58.2 and 45.2 ± 1.3 nmol for BB and BUT, respectively) vs the apical side (30.2 and 24.0 ± 1.3 nmol; P<0.001). The BB treatment had greater butyrate disappearance than BUT in 24h (254 vs 169 ± 12.6 nmol; P=0.0005) and 48h (707 vs 573 ± 12.6 nmol; P<0.0001). Gene expression showed the upregulation of sodium-glucose transport 1 (SLC5A1), monocarboxylic transporters 1& 4 (SLC16A1 & SLC16A3), and sodium hydrogen transporter 3 (SLC9A3). Along with a downregulation of 3-hydroxybutyrate dehydrogenase 1 (BDH1) and glucose transporter 2 (SLC2A2). Conclusions: BCP may promote the utilization of butyrate by intestinal epithelial cells and increase transepithelial electrical resistance. This data suggests that BCP has novel and safe therapeutic potential.