Summary:
This study is an experimental study that investigated tributyrin, a precursor to the short-chain fatty acid butyrate, using validated models of the human gastrointestinal tract. Short-chain fatty acids, also known as postbiotics, are non-living microbial products that can provide health benefits similar to probiotics. Butyrate is a key postbiotic produced in the colon that supports intestinal barrier function, regulates immune responses, and reduces inflammation. However, when butyrate is taken orally, most of it is absorbed before reaching the colon. Tributyrin is more resistant to digestion and is broken down into butyrate within the intestine, allowing greater delivery to the colon. Previous animal and early human studies suggest tributyrin may improve gut barrier integrity, reduce inflammation, support metabolic health, and protect against disruptions to the gut microbiome. In this study, two tributyrin formulations were tested. Both formulations remained partially stable during digestion, allowing more than half of the tributyrin to reach the colon. Over three weeks of supplementation, tributyrin increased butyrate levels, supported the growth of beneficial bacteria and altered microbial metabolic activity. Further analysis also showed improved intestinal barrier function and immune modulation following tributyrin fermentation. Together, these findings suggest that tributyrin is an effective way to increase colonic butyrate levels and may be a practical alternative to direct butyrate supplementation.
Abstract:
Background/objectives: Oral butyrate is unstable during upper gastrointestinal tract (GIT) transit and very little reaches the colon. Tributyrin, a butyrate precursor, resists gastric acid and is converted to butyrate by pancreatic lipases. This study aimed to quantify tributyrin stability during upper GIT passage and to uncover the effects of tributyrin supplementation on the human gut microbiome and cellular responses. Methods: In vitro upper GIT simulations were used to evaluate the stability of a capsule and softgel formulation of tributyrin (CoreBiome®). The effects of tributyrin supplementation on the human gut microbiome and cellular responses were evaluated using the Simulator of the Human Intestinal Microbial Environment (SHIME®) model and Caco-2/THP1 co-cultures. Results: The upper GIT simulations showed that 40.9 and 48.7% of the tributyrin dose administered via the capsule or softgel, respectively, was hydrolyzed to butyrate in the small intestine; 59.1 and 51.3% remained stable and was available to enter the colon. Using the SHIME® model, it was shown that 3 weeks of daily tributyrin supplementation increased butyrate levels and enhanced the abundance of several bacterial species, including Bifidobacterium spp. and Akkermansia mucinophila. Metabolic impacts on the gut microbiome were also observed. Assessment of cellular responses revealed that tributyrin fermentation had a protective effect on the intestinal barrier and exerted immunomodulatory properties. Conclusion: Enhanced butyrate concentrations and beneficial impacts on the gut microbial community composition were observed in an in vitro simulation of the human intestinal environment, suggesting that tributyrin could be considered as a solid alternative to butyrate supplementation.
Article Publication Date: 24/11/2025
DOI: 10.3389/fnut.2025.1712993
