Intestinal epithelial adaptations to vertical sleeve gastrectomy defined at single-cell resolution

• Published in: Genomics (San Diego, Calif.) Calif.), 2024-03, Vol.116 (2), p.110805, Article 110805
• Main Authors: Koch-Laskowski, Kieran, Kim, Ki-Suk, Bethea, Maigen, Fuller, Kelly N.Z., Sandoval, Darleen A., Sethupathy, Praveen
• Format: Article
• Language: English
• Subjects: Animals; Bariatric surgery; Diet, High-Fat - adverse effects; Gastrectomy - methods; Humans; Intestinal Mucosa - metabolism; Intestine; Mice; Obesity; Single-cell transcriptomics; Vertical sleeve gastrectomy
• ISSN: 0888-7543; 1089-8646; 1089-8646
• DOI: 10.1016/j.ygeno.2024.110805

The gut plays a key role in regulating metabolic health. Dietary factors disrupt intestinal physiology and contribute to obesity and diabetes, whereas bariatric procedures such as vertical sleeve gastrectomy (VSG) cause gut adaptations that induce robust metabolic improvements. However, our understanding of these adaptations at the cellular and molecular levels remains limited. In a validated murine model, we leverage single-cell transcriptomics to determine how VSG impacts different cell lineages of the small intestinal epithelium. We define cell type-specific genes and pathways that VSG rescues from high-fat diet perturbation and characterize additional rescue-independent changes brought about by VSG. We show that Paneth cells have increased expression of the gut peptide Reg3g after VSG. We also find that VSG restores pathways pertaining to mitochondrial respiration and cellular metabolism, especially within crypt-based cells. Overall, our study provides unprecedented molecular resolution of VSG's therapeutic effects on the gut epithelium. •Single-cell analysis provides a novel view of gut responses to bariatric surgery.•Surgery-induced rescue of gene expression occurs primarily in crypt lineages.•Diet perturbs while surgery restores stem and Paneth metabolic signatures.•Mitochondrial electron transport chain genes are prominently rescued by surgery.