Tributyrin (CoreBiome® Butyrate Prodrug)

Tributyrin (glycerol tributyrate, glyceryl tributyrate)
Evidence Level
Limited
3 Clinical Trials
5 Documented Benefits
2/5 Evidence Score

Tributyrin is a triglyceride of three butyrate molecules on a glycerol backbone — a butyrate prodrug that resists gastric acid and is hydrolyzed by pancreatic lipase to release butyrate further down the GI tract. The pharmacokinetic point: free butyrate (sodium butyrate) is absorbed in the upper GI before reaching the colon, while tributyrin delivers roughly 50-60% of its butyrate to the colon. Commercialized as CoreBiome® by Compound Solutions. Most evidence is in vitro (SHIME® model); the only registered human RCT was terminated due to loss of funding.

Studied Dose 300-1,000 mg/day with meals (CoreBiome®).
Active Compound Tributyrin — triglyceride of glycerol + 3 butyric acid molecules; hydrolyzed by pancreatic lipase to free butyrate + glycerol. Distinct from sodium butyrate (free butyrate salt, rapidly absorbed).

Benefits

Colonic butyrate delivery vs free butyrate (SHIME®)

In a Triple-L-SHIME® gut simulation model using 3 healthy donor microbiomes, the capsule formulation was 40.9% hydrolyzed in the small intestine with 59.1% reaching the colon (softgel: 48.7% / 51.3%). By contrast, free butyrate (sodium butyrate) is rapidly absorbed in the upper GI and very little reaches the colon — the underlying rationale for using a triglyceride prodrug instead of free butyrate.

Microbiome and inflammation effects (in vitro)

In the same Triple-L-SHIME® + Caco-2/THP1 co-culture model, daily tributyrin increased butyrate production, enriched butyrate-producer bacteria including Faecalibacterium prausnitzii and Anaerostipes, increased IL-10, decreased TNF-α, and protected against inflammation-induced intestinal barrier disruption. Effects emerged later in the treatment period, suggesting longer-term administration matters. All findings are in vitro — human translation is not yet established.

Postbiotic concept

Per the ISAPP definition, tributyrin qualifies as a postbiotic — directly delivering a beneficial bacterial fermentation metabolite (butyrate) without requiring a fiber substrate or live bacteria. Useful framing for individuals with low fiber tolerance or low microbial diversity who can't reliably ferment fiber to butyrate themselves.

Colonocyte energy substrate

Butyrate is the primary energy source for colonocytes, supplying 60-70% of their energy needs. Adequate colonic butyrate supports normal colonic epithelial cell function. Whether oral tributyrin meaningfully increases colonocyte butyrate availability in humans has not been demonstrated in clinical trials.

Stomach-acid resistance and odorless formulation

The triglyceride form resists gastric acid degradation and is odorless — addressing two practical limitations of free butyrate (sodium butyrate has an unpleasant odor and is degraded/absorbed before reaching the colon). Formulation advantage rather than efficacy claim.

Mechanism of action

1

Pancreatic lipase hydrolysis to colonic butyrate

The triglyceride structure resists gastric acidity. Pancreatic lipase in the small intestine hydrolyzes tributyrin to release butyrate progressively, allowing a portion to reach the colon. This is the distinguishing pharmacokinetic advantage over free butyrate salts.

2

HDAC inhibition by butyrate

Butyrate inhibits histone deacetylases (HDACs), modifying gene expression with anti-inflammatory and preclinically demonstrated anti-tumor effects in colorectal models. The HDAC mechanism applies to butyrate generally — not specific to tributyrin.

3

Tight junction integrity and NF-κB anti-inflammatory effects

Butyrate enhances tight junction protein expression (claudins, occludin, ZO-1) in intestinal epithelium and downregulates NF-κB-mediated inflammation, with corresponding effects reported in Caco-2/THP1 co-cultures.

4

GPR41 / GPR43 short-chain fatty acid receptor activation

Butyrate activates GPR41 (FFAR3) and GPR43 (FFAR2) on enteroendocrine cells, immune cells, and adipocytes — modulating GLP-1, PYY release, and immune signaling. Standard butyrate biology applicable via tributyrin.

Clinical trials

1
PMC12746503 — CoreBiome® Tributyrin SHIME® + Caco-2/THP1 (Pivotal In Vitro)

Frontiers in, doi:10.3389/fnut.2025.1712993.

Clinical population described in trial publication.

Frontiers in, doi:10.3389/fnut.2025.1712993. Upper GI tract simulation + Triple-L-SHIME® gut model with 3 healthy donor microbiomes + Caco-2/THP1 co-cultures. Capsule (300 mg) and softgel (450 mg) CoreBiome® formulations. Capsule: 40.9% small-intestinal hydrolysis, 59.1% colonic delivery. Softgel: 48.7% / 51.3%. Increased butyrate, enriched F. prausnitzii and Anaerostipes, increased IL-10, decreased TNF-α, protection from inflammation-induced barrier disruption. In vitro evidence — pivotal for the ingredient but not human.

2
NCT06501898 — CoreBiome® FSU 4-Week Crossover Clinical Trial (terminated)

Florida State University randomized triple-masked crossover trial, planned 300 mg/day CoreBiome® for 4 weeks in sedentary adults with outcomes including metabolite concentrations, gut permeability, inflammation, sleep, and performance.

Clinical population described in trial publication.

Florida State University randomized triple-masked crossover trial, planned 300 mg/day CoreBiome® for 4 weeks in sedentary adults with outcomes including metabolite concentrations, gut permeability, inflammation, sleep, and performance. Trial was terminated due to loss of funding — no outcome data was published. This was the only registered human clinical trial of CoreBiome®.

3
Tributyrin Anticarcinogenic Review (Preclinical)

Clinical evidence on Tributyrin (CoreBiome® Butyrate Prodrug) for the indications and outcomes described.

Clinical population described in trial publication.

Heidor R et al. 2012, Curr Drug Targets 13:1720-1729. Review of tributyrin anticarcinogenic actions focused on colorectal cancer prevention. Preclinical only — animal models and cell lines. No human cancer prevention trials of tributyrin have been conducted.

Side effects and drug interactions

Common Potential side effects

Generally well-tolerated; food-grade glyceride source.
GI upset, mild diarrhea (occasional, especially at higher doses).
Mild bitter/rancid taste (less than free butyrate).
Pregnancy/lactation: limited specific data; precautionary avoidance.
Long-term safety: limited extended-trial human data.
Allergic reactions (rare).
Industry-sponsorship (Compound Solutions for CoreBiome®) — important context.

Important Drug interactions

Most medications: well-tolerated combination profile.
Pancreatic enzyme deficiency: reduced hydrolysis efficiency — consider digestive enzymes.
Antibiotics: may reduce gut-microbiome-mediated effects (but tributyrin is direct butyrate source, not microbiome-dependent).
Anti-inflammatory medications: theoretical complementary effects in IBD.
Antidiabetic medications: theoretical compatible effects via SCFA-GPR41/43 mechanisms.

Frequently asked questions about Tributyrin (CoreBiome® Butyrate Prodrug)

What is Tributyrin?

Tributyrin is a triglyceride of three butyrate molecules on a glycerol backbone — a butyrate prodrug that resists gastric acid and is hydrolyzed by pancreatic lipase to release butyrate further down the GI tract.

What is Tributyrin used for?

Tributyrin is researched primarily for Gut Health, Anti-Inflammatory, and Metabolic Health. In a Triple-L-SHIME® gut simulation model using 3 healthy donor microbiomes, the capsule formulation was 40.9% hydrolyzed in the small intestine with 59.1% reaching the colon (softgel: 48.7% / 51.3%).

What is the recommended dosage of Tributyrin?

The clinically studied dose is 300-1,000 mg/day with meals (CoreBiome®). Always follow the product label and check with a healthcare provider for personal advice.

Is Tributyrin safe, and does it have side effects?

For most healthy adults, Tributyrin is well tolerated at studied doses. Reported effects can include: Generally well-tolerated; food-grade glyceride source. GI upset, mild diarrhea (occasional, especially at higher doses). It may also interact with some medications. Tributyrin is not right for everyone, so check with a healthcare provider first if you are pregnant or breastfeeding, have a medical condition, or take prescription medication.

Does Tributyrin interact with any medications?

Possible interactions include: Most medications: well-tolerated combination profile. Pancreatic enzyme deficiency: reduced hydrolysis efficiency — consider digestive enzymes. If you take prescription medication, check with a pharmacist or doctor before using it.

How strong is the scientific evidence for Tributyrin?

NutraSmarts rates the evidence for Tributyrin as Limited (2 out of 5). It is backed by 3 clinical trials and 3 cited references summarized on this page. A higher rating reflects more, larger, and better-designed human studies.

References(3 citations)

Evidence ratings on NutraSmarts are based on the totality of human clinical research, with emphasis on randomized controlled trials, meta-analyses, and systematic reviews. The references below directly support claims made throughout this page.

  1. Duysburgh C, Verstrepen L, Van Meulebroek L, Marzorati M Tributyrin (CoreBiome®) enhances butyrate levels and modulates the gut microbiota, barrier function, and immune response in vitro Front Nutr. 2025;12:1712993. doi:10.3389/fnut.2025.1712993.PubMedUsed to support: In vitro study using the SHIME® colonic model and Caco-2/THP1 co-cultures showing CoreBiome® tributyrin significantly elevates colonic butyrate, modulates gut microbiota composition, reinforces epithelial barrier integrity, and reduces inflammatory markers; supports colonic butyrate delivery and gut barrier benefits.
  2. Cresci GA, Bush K, Nagy LE Tributyrin supplementation protects mice from acute ethanol-induced gut injury Alcohol Clin Exp Res. 2014;38(6):1489-1501. doi:10.1111/acer.12428.PubMedUsed to support: Animal study demonstrating tributyrin supplementation protects intestinal mucosa, supports colonocyte energy substrate function, and preserves gut barrier integrity; provides preclinical mechanistic basis for tributyrin as a butyrate prodrug benefiting colonic health.
  3. Korenblik V, Korosi A, Brul S, Bockting C, Nieuwdorp M, Lok A Feasibility and acceptability of 8-week oral tributyrin supplementation as add-on to antidepressant medication in patients with depression: a study protocol paper for a pilot, randomised controlled trial BMJ Open. 2025;15(11):e108423. doi:10.1136/bmjopen-2025-108423.PubMedUsed to support: Human RCT protocol (pilot feasibility trial) testing 8-week oral tributyrin supplementation via gut-brain axis in patients with depression; documents that human clinical evaluation of tributyrin is underway and supports the postbiotic/systemic benefit concept.