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

PPID in horses is associated with selective fecal SCFA alterations, supporting a potential microbiota-gut-brain axis role.

This prospective case-control study investigated whether horses with pituitary pars intermedia dysfunction (PPID) exhibit alterations in fecal short-chain fatty acid (SCFA) profiles analogous to those observed in Parkinson disease, with which PPID shares key pathogenetic features including dopaminergic neurodegeneration and α-synuclein aggregation. Twenty-two horses over 12 years of age were enrolled (9 PPID-positive, 13 controls), with PPID diagnosis confirmed via clinical signs and thyrotropin-releasing hormone (TRH) stimulation testing. Fecal samples were collected bimonthly over 12 months and analyzed for six SCFAs—butyrate, propionate, acetate, valerate, isobutyrate, and isovalerate—using liquid chromatography-mass spectrometry, with results normalized to total protein concentration. A linear mixed-effects model revealed that month significantly influenced all SCFA concentrations across both groups, indicating pronounced seasonal variation. PPID status was independently associated with significantly elevated concentrations of butyrate, valerate, and isobutyrate compared to controls. These selective SCFA alterations suggest dysregulation of microbial fermentation in PPID-affected horses and support the potential involvement of a microbiota-gut-brain axis in PPID pathogenesis. The findings parallel gut microbiome changes documented in human neurodegenerative conditions and expand understanding of the systemic metabolic consequences of PPID beyond the endocrine system. Further research is warranted to clarify whether these microbial metabolic shifts contribute to disease progression or represent secondary effects of the condition.

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