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

OBJECTIVE: Pituitary pars intermedia dysfunction (PPID) is a prevalent endocrine disease in older horses sharing pathogenetic features with Parkinson disease, including dopaminergic neurodegeneration and α-synuclein aggregation. This study was conducted to determine whether horses with PPID exhibit changes in short-chain fatty acid (SCFA) profiles as described in Parkinson disease, providing further evidence for involvement of a microbiota-gut-brain axis in the pathogenesis of PPID. METHODS: Prospective case-control study including 22 horses > 12 years of age. Diagnosis of PPID was based on clinical signs and results of a thyrotropin-releasing hormone stimulation test. Fecal samples were collected every 2 months for 12 months, and SCFA concentrations (butyrate, propionate, acetate, valerate, isobutyrate, and isovalerate) were quantified using liquid chromatography-mass spectrometry. Data were normalized to sample total protein concentration and analyzed using a linear mixed-effects model with Šídák multiple comparison tests. RESULTS: 9 horses were classified as PPID and 13 as controls. Month had a significant effect on concentrations of all measured SCFA across both groups. The PPID status was associated with significantly altered patterns in concentrations of butyrate (average estimate of difference: 0.30 μM/mg; 95% CI, 0.02 to 0.58), valerate (0.04 μM/mg; 95% CI, 0.01 to 0.08), and isobutyrate (0.10 μM/mg; 95% CI, 0.04 to 0.17). CONCLUSIONS: Horses exhibit marked seasonal variations in fecal SCFA concentrations, and PPID is associated with selective alterations in fecal SCFA profiles. CLINICAL RELEVANCE: Altered fecal SCFA profiles in horses with PPID expand our understanding of metabolic changes associated with this condition and warrant further investigation into the relationship between microbial metabolism and the microbiota-gut-brain axis in PPID.