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Butyrate (Tributyrin)

supporting gut health and colon cell function

supplement
Meta-analysis availableSystematic review availableHuman trial evidenceNeeds more research

Short-chain fatty acid fueling colonocytes and gut barrier.

Butyrate, a short-chain fatty acid, is primarily produced in the colon through the bacterial fermentation of dietary fiber. It serves as a crucial energy source for colonocytes (cells lining the colon) and plays a role in maintaining gut barrier integrity. Tributyrin is a triglyceride form of butyrate, designed to deliver butyrate more effectively to the lower gastrointestinal tract, as free butyrate can be rapidly absorbed in the upper gut. While butyrate is naturally present in the body, supplementation with tributyrin aims to increase its concentration in the colon, where it may exert various beneficial effects.

Quick answer

What it is: Butyrate, a short-chain fatty acid, is primarily produced in the colon through the bacterial fermentation of dietary fiber.

May support:Leaky Gut Syndrome, Ulcerative Colitis, Inflammatory Bowel Disease

Evidence Summary

The current understanding of butyrate and tributyrin is largely based on foundational biochemical research, in vitro studies, and animal models. While these studies provide insights into potential mechanisms and effects, there is a lack of robust human clinical trials specifically investigating tributyrin for various health conditions. Therefore, claims regarding efficacy in humans are currently theoretical or based on indirect evidence.

Last reviewed · Jun 2026

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Why It Works

Primary energy source for colon cells; HDAC inhibitor.

How it works in more detail

Butyrate is a histone deacetylase (HDAC) inhibitor, which can alter gene expression by increasing histone acetylation, potentially influencing cell proliferation, differentiation, and apoptosis. It also acts as a ligand for G-protein coupled receptors (GPCRs) like GPR41, GPR43, and GPR109A, which are involved in immune regulation and energy metabolism. By providing energy to colonocytes, butyrate helps maintain the integrity of the intestinal barrier, reducing permeability and potentially mitigating inflammation. Its anti-inflammatory effects are also mediated by inhibiting NF-κB activation.

How to use

Always consult a qualified clinician.

Editorial guidance

Suggested dosage
300–1200 mg/day
Typical forms
capsule, powder
Quality markers
When purchasing tributyrin, look for products from reputable manufacturers that provide third-party testing for purity and potency. The form of tributyrin (e.g., microencapsulated) may influence its delivery to the colon. Check for clear labeling of the butyrate content.

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Suggested dosage

300–1200 mg/day

General guidance — discuss specifics with a clinician.

Active medicinal compounds

Butyrate (as tributyrin)

Safety

Safety warnings

Generally safe; odor common.

Reported side effects

  • mild gastrointestinal discomfort
  • bloating
  • gas

General guidance — discuss specifics with a clinician.

Evidence ecosystem

Scientific literature, clinical guidance, government sources, ongoing research, traditional use, and lived experience — grouped by source type and quality.

Overall grade

The current understanding of butyrate and tributyrin is largely based on foundational biochemical research, in vitro studies, and animal models. While these studies provide insights into potential mechanisms and effects, there is a lack of robust human clinical trials specifically investigating tributyrin for various health conditions. Therefore, claims regarding efficacy in humans are currently theoretical or based on indirect evidence.

Filter by source type

Meta-Analyses(1)

Pooled analyses across multiple human trials.

Very High Quality
  • Gut dysbiosis in rheumatic diseases: A systematic review and meta-analysis of 92 observational studies.

    Wang Y, Wei J, Zhang W, Doherty M, Zhang Y, Xie H · EBioMedicine · 2022 · n=998

    Emerging evidence suggests that dysbiosis in gut microbiota may contribute to the occurrence or development of several rheumatic diseases. Since gut microbiota dysbiosis is potentially modifiable, it has been postulated to be a promising preventive or therapeutic target for rheumatic diseases. However, the current understanding on the potential associations between gut microbiota and rheumatic diseases is still inadequate. Therefore, we aimed to synthesise the accumulating evidence for the relation of gut microbiota to rheumatic diseases. The PubMed, Embase and Cochrane Library were searched from inception to March 11, 2022 to include observational studies evaluating the associations between gut microbiota and rheumatic diseases. Standardised mean difference (SMD) of α-diversity indices between rheumatic diseases and controls were estimated using random-effects model. β-diversity indices and relative abundance of gut microbes were summarised qualitatively. Of the included

    Meta-AnalysisPubMedVery High Quality

Systematic Reviews(1)

Structured reviews of the full body of evidence (incl. Cochrane).

Very High Quality
  • Clostridium butyricum and its metabolites regulate macrophage polarization through miR-146a to antagonize gouty arthritis.

    Song S, Shi K, Fan M, Wen X, Li J, Guo Y · Journal of advanced research · 2026

    Gut microbiota modulation has recently been identified as a prospective avenue for the exploration of novel therapeutic strategies for the management of gout. Nevertheless, the application of a single specific strain or bacterial metabolite for gout intervention has rarely been explored and the underlying regulatory mechanism remains elusive. To ascertain the potential role and the molecular mechanism of Clostridium butyricum and butyrate in the management of gouty arthritis. A Uox-KO mouse model of gouty arthritis was developed and the composition of the gut microbiota was analyzed. C. butyricum and butyrate were supplemented to assess functional recovery and intestinal homeostasis. NanoString analysis identified miRNA variations. GC/MS measured butyric acid levels and qPCR detected the abundance of butyrate-producing enzymes and bacteria. Flow cytometry analyzed macrophage polarization and ELISA measured pro-inflammatory cytokine production. Agomir and antagomir were transfected an

    Systematic ReviewPubMedVery High Quality

Randomized Human Trials(6)

Controlled human studies with random assignment.

High Quality
  • Efficacy of a postbiotic and its components in promoting colonic transit and alleviating chronic constipation in humans and mice.

    Ma T, Li Y, Yang N, Wang H, Shi X, Liu Y · Cell reports. Medicine · 2025 · n=110

    This study evaluates the efficacy of the postbiotic Probio-Eco in alleviating constipation in humans and mice. A randomized, double-blind, placebo-controlled crossover trial involving 110 adults with chronic constipation (Rome IV criteria) demonstrates that a 3-week Probio-Eco intervention significantly improves constipation symptoms, stool straining, and worry scores. Gut microbiota and metabolomic analyses reveal modulations in specific gut microbiota, succinate, tryptophan derivatives, deoxycholate, propionate, butyrate, and cortisol, correlating with symptom relief. A loperamide-induced mouse model confirms that Probio-Eco and its bioactive components (succinate, 3-indoleacrylic acid, and 5-hydroxytryptophan) alleviate constipation by stimulating mucin-2 secretion, regulating intestinal transport hormones, and promoting anti-inflammatory responses. Multi-omics integration identifies key pathways, including succinate-short-chain fatty acid, tryptophan-5-hydroxytryptophan-serotonin,

    Randomized TrialPubMedHigh Quality
  • Effects of short-chain fatty acid-producing probiotic metabolites on symptom relief and intestinal barrier function in patients with irritable bowel syndrome: a double-blind, randomized controlled trial.

    Li E, Wang J, Guo B, Zhang W · Frontiers in cellular and infection microbiology · 2025

    IBS often appears as bloating, altered bowel patterns, and abdominal pain (AP).Probiotics and SCFA may be useful in mucosal repair and symptom relief, according to earlier research, however there is currently a lack of systematic evidence supporting their therapeutic effectiveness across a variety of IBS subtypes. To investigate the impacts of probiotics on signs and intestinal barrier function (IBF) in individuals with multiple IBS subtypes, and evaluate the role of SCFA in this process. A double-blind randomized controlled trial (DBRCT) design was adopted. Using the Rome IV criteria, a total of 120 individuals with IBS were randomised to either the probiotic group (PG) or placebo group (PLG). The intervention lasted for 12 weeks with an additional 4-week follow-up. In addition to fecal SCFA (FSCFA) levels, intestinal permeability (L/M ratio), tight junction proteins (TJP), serum/fecal inflammatory markers, and adverse event occurrence, the primary endpoint (PEP) evaluated was IBS S

    Randomized TrialPubMedHigh Quality
  • Nutritional Management in Stricturing Crohn's Disease: A Pilot Study.

    Cavalcanti E, Marra A, Mileti A, Donghia R, Curlo M, Mastronardi M · Nutrients · 2024

    More than half of patients with Crohn's disease develop intestinal fibrosis induced intestinal obstruction with debilitating symptoms throughout their disease course. The incidence of stricture formation in CD has remained unchanged over the last several decades. Factors promoting intestinal fibrosis are currently unclear, but diet may represent an underestimated risk factor for intestinal fibrosis by modification of both the host immune response and intestinal microbial composition. Evaluating the impact of diet on the course of IBD is very complex. Sarcopenia is a common problem in IBD patients and correlates with an increased rate of disease. Skeletal muscle index (SMI) is an important parameter to measure sarcopenia and is an easily accessible tool for evaluating the likelihood of complications in individuals with CD. Using a randomized and controlled pilot design, we aimed to investigate the efficacy of 12 months of short-term dietary intervention based on essential amino acid (E

    Randomized TrialPubMedHigh Quality

Observational Studies(3)

Cohort, case-control, and cross-sectional human studies.

Moderate Quality
  • Gout, Hyperuricemia, and the Intestinal Microbiome.

    Renton N, Pillinger MH, Toprover M · Inflammation · 2025

    Gout is a disease of hyperuricemia (HU) leading to monosodium urate crystal deposition in the joint, resulting in inflammation and joint damage. Recently, efforts have been made to characterize the intestinal microbiome of patients who suffer from HU and gout, and pre-clinical studies have evaluated the utility of prebiotics and probiotics in alleviating gout. Herein we review recent notable studies addressing these topics. In brief, the "gouty" microbiome is characterized by reduced diversity, an elevated Bacteroides: Firmicutes ratio, and reduced presence of Akkermansia and Bifidobacterium. In anserine models, supplementation with Lactobacillus probiotic strains appears to reduce serum urate (SU) and HU-induced inflammation. Murine models suggest that the chicory-derived prebiotic inulin may reduce SU, and oral supplementation with the anti-inflammatory short-chain fatty acid butyrate may lower SU by enhancing urate excretion and alleviate HU-induced tissue inflammation. Many of thes

    Observational StudyPubMedLow Quality
  • Deficient butyrate-producing capacity in the gut microbiome is associated with bacterial network disturbances and fatigue symptoms in ME/CFS.

    Guo C, Che X, Briese T, Ranjan A, Allicock O, Yates RA · Cell host & microbe · 2023

    Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is characterized by unexplained debilitating fatigue, cognitive dysfunction, gastrointestinal disturbances, and orthostatic intolerance. Here, we report a multi-omic analysis of a geographically diverse cohort of 106 cases and 91 healthy controls that revealed differences in gut microbiome diversity, abundances, functional pathways, and interactions. Faecalibacterium prausnitzii and Eubacterium rectale, which are both recognized as abundant, health-promoting butyrate producers in the human gut, were reduced in ME/CFS. Functional metagenomics, qPCR, and metabolomics of fecal short-chain fatty acids confirmed a deficient microbial capacity for butyrate synthesis. Microbiome-based machine learning classifier models were robust to geographic variation and generalizable in a validation cohort. The abundance of Faecalibacterium prausnitzii was inversely associated with fatigue severity. These findings demonstrate the functional natu

    Observational StudyPubMedLow Quality
  • Dietary supplements for intestinal inflammation.

    Kiani AK, Bonetti G, Donato K, Bertelli M · Journal of preventive medicine and hygiene · 2022

    Intestinal inflammation leads to various chronic diseases, collectively known as inflammatory bowel disease (IBD). IBD mainly affects the large intestine, but it can also affect the gastrointestinal tract as a whole. Its major symptoms are pain, diarrhea, and weight loss, and it is usually associated with deficiencies of both macro- and micronutrients. Unluckily, after some time the body develops resistance against the already available drugs: thus, many patients fail to maintain remission, which is achieved in less than 50% of cases. Diet is a major determinant of gut inflammation. An unbalanced diet can affect the gut microbiota and cause dysbiosis, which is related to a dysregulated host immune response. The Mediterranean Diet its renowned for its anti-inflammatory effects and for preventing dysbiosis. In order to improve management and treatment of intestinal inflammatory diseases, it should become common practice to integrate the patient's diet with dietary supplements with anti-i

    Observational StudyPubMedLow Quality

Animal Studies(1)

Preclinical animal research — not a substitute for human evidence.

Low Quality
  • Gut dysbiosis is linked to hypertension.

    Yang T, Santisteban MM, Rodriguez V, Li E, Ahmari N, Carvajal JM · Hypertension (Dallas, Tex. : 1979) · 2015

    Emerging evidence suggests that gut microbiota is critical in the maintenance of physiological homeostasis. This study was designed to test the hypothesis that dysbiosis in gut microbiota is associated with hypertension because genetic, environmental, and dietary factors profoundly influence both gut microbiota and blood pressure. Bacterial DNA from fecal samples of 2 rat models of hypertension and a small cohort of patients was used for bacterial genomic analysis. We observed a significant decrease in microbial richness, diversity, and evenness in the spontaneously hypertensive rat, in addition to an increased Firmicutes/Bacteroidetes ratio. These changes were accompanied by decreases in acetate- and butyrate-producing bacteria. In addition, the microbiota of a small cohort of human hypertensive patients was found to follow a similar dysbiotic pattern, as it was less rich and diverse than that of control subjects. Similar changes in gut microbiota were observed in the chronic angioten

    Animal StudyPubMedLow Quality

Clinical Trial Registries(4)

Registered ongoing or completed trials (ClinicalTrials.gov).

Moderate Quality
  • A Study to Evaluate the Effects of a Butyrate-Polyphenol Formulation on Gut Health and Associated Symptoms

    n=124 · NCT07371975 · RECRUITING · RECRUITING

    The purpose of the study is to evaluate the efficacy of a butyrate/polyphenol formulation on modulation of the gut microbiome and gastrointestinal symptoms using questionnaires in individuals with self-reported gastrointestinal discomfort.

    Clinical TrialClinicalTrials.govModerate Quality
  • The Effects of a Postbiotic Supplement on Biomarkers of Gastrointestinal, Cardiometabolic and Immunometabolic Health

    n=76 · NCT07527286 · COMPLETED · COMPLETED

    This study is a randomized, double-blind, two-arm, placebo-controlled trial of N=80 (40/arm) apparently healthy men and women between 18 and 65 years old to be recruited at a single investigational center in Northeast Ohio (i.e., The Center for Applied Health Sciences). This study will assess the effectiveness of a postbiotic supplement on various biomarkers of health. Consumption of this dietary supplement is not intended to diagnose, treat, cure, or prevent any disease. Participants will attend three in-person study visits. During Visit 1, participants will be screened for participation (i.e., medical history, routine blood work, background baseline diet). Over the next 4 weeks, participants will attend two in-person visits: \[visit 2 (week 0) and visit 3 (week 4)\] wherein assessments of gut function \[fecal microbiome diversity, short chain fatty acids (SCFA), and fecal butyrate\], serum butyrate, serum zonulin, salivary cortisol, and Gastrointestinal Symptom Rating Scale (GSRS) for gastrointestinal (GI) health, emotional states \[Depression, Anxiety and Stress Scale (DASS21)\], and quality of life (SF-36 questionnaire) will be assessed. Participants will also be provided home kits with instructions on how to collect stool and saliva samples on two separate occasions (i.e., visit 2, visit 3) during the study. • Comprehensive side effect profile/ adverse event monitoring will take place throughout the study duration. The study will be conducted following ICH-GCP guidelines to ensure participant safety and scientific integrity of the data.

    Clinical TrialClinicalTrials.govModerate Quality
  • A Double-blind, Randomized, Placebo-controlled Study to Evaluate the Effects of a Butyrate Formulation and a Butyrate + Polyphenol Formulation on Gut Health, Permeability and Associated Symptoms

    n=143 · NCT06419231 · COMPLETED · COMPLETED

    The purpose of this study is the assess the effectiveness and safety of a Butyrate formulation and a Butyrate + Polyphenol formulation on gut health, permeability and associated symptoms

    Clinical TrialClinicalTrials.govModerate Quality

Limitations: A significant limitation is the absence of direct human clinical trials for tributyrin in many areas of potential application. Existing research often uses free butyrate or focuses on animal models, which may not directly translate to human physiology or clinical outcomes. More human studies are needed to establish efficacy, optimal dosages, and long-term safety.

This page is educational. Statements use phrases like "may support" and "has been studied for"because no remedy here is approved to cure, treat, or reverse any condition. Discussion happens on the ailment pages — community statistics here are derived from those reports. Always consult a qualified clinician.

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