SFEBES2026 Oral Communications Metabolism, Obesity and Diabetes (6 abstracts)
Decoding the obese duodenal cell atlas
Yuxian Lei 1 , Daniela Pirri 2 , Yufan Liu 2 , Balazs Bohar 2 , Rubin George 3 , Lee Meng Choong 3 , Bu Hayee 3 , Tamas Korcsmaros 2 , Kevin Murphy 2 & Gavin Bewick 1
1King’s College London, London, United Kingdom; 2Imperial College London, London, United Kingdom; 3King’s College Hospital, London, United Kingdom
The duodenum is an active regulator of metabolic homeostasis, shown by rapid glycaemic improvements after procedures altering proximal nutrient flow even before weight loss, yet the obesity associated cellular, molecular, and microenvironmental changes that drive barrier, hormonal, and immune dysfunction remain poorly defined. To define cellular pathology of the obese human duodenum, we conducted a pilot single-cell RNA-sequencing study in 28 individuals: 14 with obesity (BMI ≥ 35) and 14 lean (BMI < 25). Duodenal biopsies were collected over 6 months. Freshly dissociated cells underwent magnetic-activated cell sorting (MACS) to enrich epithelial and immune compartments, followed by fixation to preserve RNA integrity for downstream processing. MACS-enriched samples yielded greater cellular diversity. In contrast, non-enriched samples showed marked depletion of total epithelial cells and loss of key epithelial subsets, including stem cells, transit-amplifying (TA) cells, and Paneth cells. Sequencing data were processed in Trailmaker� and visualized using Scanpy. 47,744 high-quality cells were retained after quality control, including mitochondrial read-content filtering (>50%) and doublet removal (scDblFinder). The retained cells were then normalized, batch-corrected/integrated (Harmony), and clustered using Leiden (resolution 1.5). The epithelial compartment comprised five enterocyte subtypes, goblet, tuft, BEST4+ enterocytes, microfold cells, Paneth, TA, stem, and enteroendocrine cells. Immune populations included cytotoxic T cells, CD8+ and CD4+ T cells, NKT cells, B cells, T- and B-memory cells, Tregs, exhausted T cells, macrophages, mast cells, and dendritic cells. Cluster proportions were broadly comparable between females and males; however, cytotoxic T cells, memory T cells, CD8+ T cells, and enterocytes exhibited potential sex-associated differences. Collectively, this pilot establishes technical feasibility for duodenal biopsy acquisition and processing compatible with longitudinal sampling and downstream multi-omic profiling. The full study will expand the atlas to ~600k cells, enabling mapping of cellular and transcriptomic remodelling at the epithelial interface and revealing how they shape the obesity-related metabolic responses.
Volume 117
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Endocrine Abstracts
ISSN 1470-3947 (print) | ISSN 1479-6848 (online)
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