Distinct gut microbial profile in PIT1 lineage PitNETs: a potential link to cognitive impairment.

BACKGROUND: Patients with pituitary neuroendocrine tumors (PitNETs) frequently experience cognitive impairment (CI), yet the underlying mechanisms remain poorly understood. METHOD: In this study, we assessed cognitive function in 42 PitNETs patients and 42 healthy controls using the Montreal Cognitive Assessment (MoCA), evaluating the effects of tumor volume, invasiveness, pituitary hormone levels, lineage, and surgical intervention.Furthermore, 16S rRNA amplicon sequencing of fecal samples was performed to reveal alterations in gut microbiota composition. RESULTS: The results demonstrated significantly lower MoCA scores in PitNETs patients compared to controls. Patients with PIT1 lineage tumors exhibited more severe CI than those with SF-1 lineage tumors. Notably, surgical treatment led to improved cognitive performance. The sequencing revealed significant alterations in gut microbiota composition in PitNETs patients. Specifically, PIT1 lineage cases showed reduced levels of the butyrate-producing genus Agathobacter and increased abundance of UBA1819 and Alistipes indistinctus, taxa that have been implicated in pro-inflammatory states. DISCUSSION: These preliminary findings suggest that PIT1-lineage PitNETs may be associated with an increased susceptibility to cognitive impairment, potentially involving interactions between hormonal dysregulation and gut microbiota dysbiosis. This exploratory hypothesis provides a conceptual framework for future research to elucidate underlying mechanisms and explore potential interventions for cognitive impairment in PitNETs.