Impact of Prolonged Fasting and Refeeding on Enteroendocrine Hormone Expression: One More Piece of the Fasting/Refeeding Metabolic Puzzle

<b>Introduction:</b> Prolonged fasting induces histological and ultrastructural changes of the intestinal mucosa that may reduce absorption in malnourished patients with high risk of refeeding syndrome. Endocrine function of the intestinal mucosa may be affected by starvation with potential implications for nutritional support. <b>Objective:</b> The present study aims to evaluate the expression of gastrointestinal hormones in duodenal enteroendocrine cells (EECs) of patients after a long starvation period and to assess the changes in EEC hormonal expression after enteral refeeding in the same individuals. <b>Methods:</b> This was an observational prospective controlled study. Adult patients submitted to endoscopic gastrostomy (PEG) with an ingestion below 50% of daily needs for at least one month were enrolled. Duodenal biopsies were collected before gastrostomy (T0) and after 3-6 months of PEG feeding (T1). Biopsies underwent immunohistochemical analysis for chromogranin-A (CgA), neurotensin and incretin (GLP-1 and GIP) tissue expression. Normal duodenum biopsies were used as controls. <b>Results:</b> A total of 30 patients (16 men/14 women) aged 67.1 ± 13.5 years were included, and 14 patients completed follow-up at both periods (46.7%). Malnutrition was diagnosed in all patients according to GLIM criteria. T0 tissue expression defined by median stained area for CgA, GLP-1, and GIP were significantly higher in patients compared to controls (CgA: 1.04% vs. 0.41%; GLP-1: 0.17% vs. 0.03%; GIP: 0.19% vs. 0.03%) (<i>p</i> < 0.001) without differences for neurotensin (0.01%) (<i>p</i> = 0.96). T1 hormonal tissue expression was not significantly reduced after 3-6 months of enteral refeeding (<i>p</i> > 0.05). <b>Conclusions:</b> Prolonged fasting induces increased expression of incretins and chromogranin-A in the duodenum that probably reflect an adaptative response to maintain the anabolic insulin effect under nutritional deficiency. Hormonal expression does not normalize after PEG refeeding during a short period.