Intratumoral microbiota in pancreatic neuroendocrine tumors: Enriched bacterial biomass and diversity with association to dyslipidemia.

BACKGROUND: Intratumoral microbiota have been implicated in several cancers, including pancreatic cancer, but data on pancreatic neuroendocrine tumors (PNETs) remain limited. METHODS: We analyzed two complementary cohorts: a retrospective formalin-fixed paraffin-embedded cohort comprising 53 primary PNETs, 26 paired adjacent non-tumor tissues (ANTs), and 5 liver metastases assessed by fluorescence in situ hybridization (FISH); and a prospective subset of 25 paired fresh tumor-center and ANT samples analyzed by 16S rRNA gene sequencing. Taxonomic composition, alpha and beta diversity, differential abundance, predicted microbial functions, and associations with clinicopathological features and fasting serum lipids were evaluated. RESULTS: PNETs showed a higher frequency of detectable bacterial signals and greater microbial richness and diversity than ANTs. LEfSe identified 38 nominally differentially abundant taxa (P < 0.05; LDA > 2.5), including enrichment of Blautia, Rothia, and Ferrovibrio in tumors. Their combined abundance differentiated PNETs from ANTs with an area under the curve of 0.843. Exploratory functional inference suggested enrichment of 15 pathways in PNETs, including fatty acid and short-chain fatty acid biosynthesis pathways. Serum high-density lipoprotein levels were inversely associated with intratumoral microbial richness (Ace index: r = -0.497, P = 0.049). CONCLUSIONS: PNETs exhibited greater bacterial burden, microbial richness, and diversity than ANTs, with distinct taxonomic patterns and lipid-related associations. These exploratory findings warrant external validation in larger cohorts with rigorous low-biomass contamination control.