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Dietary tributyrin supplementation in Parkinson's disease: An open-label target engagement study

Dietary tributyrin supplementation in Parkinson's disease: An open-label target engagement study

Jeffrey L B Bohnen ¹, Stiven Roytman ², Travis P Wigstrom ³, Robert K Vangel ², Jaime E Barr ², Giulia Carli ², Sean M Parks ⁴, Hitasha Mittal ⁵, Claire Martino ⁶, Prabesh Kanel ⁷, Roger L Albin ⁸, Nicolaas I Bohnen ⁹

Jeffrey L B Bohnen ¹, Stiven Roytman ², Travis P Wigstrom ³

¹Michigan Medicine, University of Michigan, Ann Arbor, MI, 48109, USA; Department of Neurology, University of Michigan, Ann Arbor, MI, 48109, USA; University of Michigan Medical School, Ann Arbor, MI, 48109, USA; Department of Psychiatry, University of Michigan, Ann Arbor, MI, 48109, USA.
²Department of Neurology, University of Michigan, Ann Arbor, MI, 48109, USA.
³Department of Neurology, University of Michigan, Ann Arbor, MI, 48109, USA; University of Michigan Medical School, Ann Arbor, MI, 48109, USA.
⁴University of Michigan Medical School, Ann Arbor, MI, 48109, USA.
⁵Department of Medicine and Surgery, Universita Vita Salute San Raffaele, 20132, Milan, Italy.
⁶College of Literature, Science, and the Arts, University of Michigan, Ann Arbor, MI, 48109, USA.
⁷Department of Neurology, University of Michigan, Ann Arbor, MI, 48109, USA; Department of Radiology, University of Michigan, Ann Arbor, MI, 48109, USA.
⁸Michigan Medicine, University of Michigan, Ann Arbor, MI, 48109, USA; Department of Neurology, University of Michigan, Ann Arbor, MI, 48109, USA; University of Michigan Medical School, Ann Arbor, MI, 48109, USA; Morris K. Udall Center of Excellence for Parkinson's Disease Research, University of Michigan, Ann Arbor, MI, 48109, USA; Parkinson's Foundation Research Center of Excellence, University of Michigan, Ann Arbor, MI, 48109, USA; Department of Radiology, University of Michigan, Ann Arbor, MI, 48109, USA.
⁹Michigan Medicine, University of Michigan, Ann Arbor, MI, 48109, USA; Department of Neurology, University of Michigan, Ann Arbor, MI, 48109, USA; University of Michigan Medical School, Ann Arbor, MI, 48109, USA; Neurology Service and Geriatric Research, Education, and Clinical Center, VA Ann Arbor Healthcare System, Ann Arbor, MI, 48105, USA; Morris K. Udall Center of Excellence for Parkinson's Disease Research, University of Michigan, Ann Arbor, MI, 48109, USA; Parkinson's Foundation Research Center of Excellence, University of Michigan, Ann Arbor, MI, 48109, USA; Department of Radiology, University of Michigan, Ann Arbor, MI, 48109, USA.

⁰Michigan Medicine, University of Michigan, Ann Arbor, MI, 48109, USA; Department of Neurology, University of Michigan, Ann Arbor, MI, 48109, USA; University of Michigan Medical School, Ann Arbor, MI, 48109, USA; Department of Psychiatry, University of Michigan, Ann Arbor, MI, 48109, USA.

Neurotherapeutics : the Journal of the American Society for Experimental Neurotherapeutics +

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November 21, 2025

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View abstract on PubMed

Summary

This summary is machine-generated.

Tributyrin, a prodrug of butyrate, shows promise for Parkinson's disease by improving brain butyrate levels and offering anti-inflammatory effects. This study found tributyrin safe and well-tolerated, with potential benefits for motor and cognitive symptoms.

Area Of Science

Neuroscience
Gastroenterology
Pharmacology

Background

Short-chain fatty acids like butyrate are crucial for gut-brain axis signaling and have therapeutic potential for neurodegenerative diseases.
Oral butyrate supplementation faces challenges due to rapid metabolism, leading to low systemic and brain concentrations.
Tributyrin, a butyrate prodrug, offers improved pharmacokinetics compared to sodium butyrate.

Purpose Of The Study

To assess the safety, tolerability, and target engagement of tributyrin supplementation in individuals with Parkinson's disease.
To investigate tributyrin's effects on brain butyrate uptake and systemic inflammation.
To explore potential clinical benefits of tributyrin on cognitive and motor functions in Parkinson's disease.

Main Methods

An open-label, 30-day study involving 14 Parkinson's disease patients and 3 controls receiving oral tributyrin (500 mg TID).
Positron Emission Tomography (PET) imaging with [11C]butyrate to measure organ-specific butyrate uptake before and after supplementation.
Clinical assessments of cognitive, motor, and neurobehavioral functions were performed pre- and post-intervention.

Main Results

Tributyrin supplementation demonstrated a favorable safety profile with high adherence rates.
PET imaging confirmed target engagement, showing increased butyrate uptake in various organs.
Improvements were observed in exploratory cognitive and motor assessments, alongside systemic anti-inflammatory effects.

Conclusions

Tributyrin is safe and well-tolerated in Parkinson's disease patients, with evidence of target engagement and potential clinical benefits.
Tributyrin may modulate brain butyrate availability and exert systemic anti-inflammatory effects.
Further large-scale, placebo-controlled trials are warranted to confirm tributyrin's efficacy as a complementary therapy for Parkinson's disease.

Keywords:

Butyrate Gut-brain axis Neuroimaging Parkinson’s disease Postbiotic intervention Tributyrin

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