Horses with pituitary pars intermedia dysfunction have an altered fecal short-chain fatty acid profile.

Overview

• This study investigated whether older horses with pituitary pars intermedia dysfunction (PPID), an endocrine disorder similar in some ways to Parkinson’s disease, show changes in their fecal short-chain fatty acid (SCFA) profiles, which could suggest involvement of the gut microbiota in the disease process.

Background

• PPID is a common endocrine disorder affecting older horses.
• It shares certain pathological features with Parkinson’s disease, such as dopaminergic neuron degeneration and accumulation of α-synuclein protein aggregates.
• Recent research in Parkinson’s disease suggests that alterations in gut microbiota and their metabolic products, such as SCFAs, may play a role in disease development through a microbiota-gut-brain axis.
• This study aimed to explore if similar changes in fecal SCFAs occur in horses with PPID, providing insight into microbial and metabolic influences on the disease.

Study Design and Methods

• Type: Prospective case-control study design.
• Participants: 22 horses older than 12 years were selected based on clinical signs and endocrine testing (thyrotropin-releasing hormone stimulation test) for PPID diagnosis.
• Groups: 9 horses classified with PPID and 13 as controls without PPID.
• Sample Collection: Fecal samples were collected every 2 months for one year to capture seasonal variability.
• Measurement: Concentrations of six SCFAs— butyrate, propionate, acetate, valerate, isobutyrate, and isovalerate—were quantified using liquid chromatography-mass spectrometry.
• Normalization: SCFA concentrations were normalized to total fecal protein content to account for sample variability.
• Analysis: Data were analyzed using linear mixed-effects models with Šídák multiple comparison adjustments to assess the effects of PPID status and time (season/month) on SCFA levels.

Key Findings

• Seasonal Variation: All measured SCFA concentrations varied significantly across the months in both PPID and control groups, indicating marked seasonal fluctuations in fecal SCFAs.
• PPID-associated Changes:
  • Horses with PPID had distinct alterations in certain SCFAs compared to controls.
  • Significant increases were observed in:
    • Butyrate (mean difference: 0.30 μM per mg protein)
    • Valerate (mean difference: 0.04 μM per mg protein)
    • Isobutyrate (mean difference: 0.10 μM per mg protein)
  • These differences suggest specific metabolic shifts in gut microbial activity associated with PPID rather than a generalized change in all SCFAs.

Interpretation and Implications

• The findings confirm that fecal SCFA profiles are influenced by both season and disease status in older horses.
• Altered levels of butyrate, valerate, and isobutyrate in PPID horses imply that gut microbial metabolism differs in this condition and could contribute to disease mechanisms.
• Since SCFAs are known to affect gut health, immune function, and possibly the nervous system via the microbiota-gut-brain axis, these changes may be relevant to the dopaminergic degeneration and α-synuclein pathology seen in PPID.
• This research provides a foundation for future studies to investigate:
  • How microbial composition and function are altered in PPID.
  • The role of microbial metabolites like SCFAs in progression and symptoms of PPID.
  • Potential therapeutic interventions targeting gut microbiota to improve outcomes in horses with PPID.