{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,8]],"date-time":"2026-04-08T22:09:08Z","timestamp":1775686148940,"version":"3.50.1"},"reference-count":29,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2023,12,30]],"date-time":"2023-12-30T00:00:00Z","timestamp":1703894400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"FCT\u2014Foundation for Science and Technolog","award":["UIDB\/04585\/2020"],"award-info":[{"award-number":["UIDB\/04585\/2020"]}]},{"name":"Portuguese Gastroenterology Society","award":["UIDB\/04585\/2020"],"award-info":[{"award-number":["UIDB\/04585\/2020"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Nutrients"],"abstract":"<jats:p>Background: Malnutrition is usual in patients referred for endoscopic gastrostomy (PEG). Refeeding syndrome is rarely observed in PEG-fed patients, which could possibly be associated with reduced absorption induced by prolonged starvation. Objective: In patients submitted to PEG after a significant period of fasting, the present study aims to: 1. evaluate the histological\/ultrastructural initial changes in the intestinal mucosa, potentially associated with reduced absorption, and 2. assess if these changes could reverse with enteral refeeding. Methods: The present study is an observational, prospective, controlled study. Adult patients with ingestion below 50% of daily needs for at least one month and\/or diagnosis of malnutrition were enrolled. Duodenal biopsies were taken at baseline and after 3\u20136 months of PEG feeding, which then underwent histological\/ultrastructural analysis. Random healthy individuals were used as controls. Results: A total of 30 patients (16 men\/14 women) aged 67.1 \u00b1 13.5 years were included. Malnutrition was found in 40% of patients. Approximately 14 patients completed follow-up during both periods (46.7%). At baseline: duodenal mucosal atrophy was evident in three patients (10%); the median villi length (MVL) was 0.4 mm (0.25\u20130.6 mm), with it being shorter than the controls, which was 0.6 mm (0.4\u20130.7 mm) (p = 0.006); ultrastructural changes included focal shortening, bending, and disruption of enterocyte microvilli, the presence of citoplasmatic autophagic vacuoles, dilation and vesiculation of the smooth endoplasmic reticulum, and the presence of dilated intercellular spaces with basement membrane detachment. After refeeding, most patients displayed normal histology (92.9%) and increase MVL (p &lt; 0.001), ultrastructural changes disappeared, and enterocytes resumed a normal appearance, although retaining scarce, small, dense bodies in apical regions from the evolution of previous autophagy. Conclusions: Prolonged fasting induces histological and ultrastructural changes in the intestinal mucosa that may reflect impaired absorption in the early post-PEG period. These changes were reverted after refeeding with enteral nutrition.<\/jats:p>","DOI":"10.3390\/nu16010128","type":"journal-article","created":{"date-parts":[[2023,12,31]],"date-time":"2023-12-31T04:51:51Z","timestamp":1703998311000},"page":"128","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Prolonged Fasting Induces Histological and Ultrastructural Changes in the Intestinal Mucosa That May Reduce Absorption and Revert after Enteral Refeeding"],"prefix":"10.3390","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4920-9158","authenticated-orcid":false,"given":"Gon\u00e7alo","family":"Nunes","sequence":"first","affiliation":[{"name":"Gastroenterology Department, GENE\u2014Artificial Feeding Team, Hospital Garcia de Orta, 2805-267 Almada, Portugal"},{"name":"ICBAS-UP\u2014Instituto de Ci\u00eancias Biom\u00e9dicas Abel Salazar, Universidade do Porto, 4050-313 Porto, Portugal"},{"name":"PaMNEC\u2014Grupo de Patologia M\u00e9dica, Nutri\u00e7\u00e3o e Estudos Cl\u00ednicos, Egas Moniz Center for Interdisciplinary Research (CiiEM), Egas Moniz School of Health and Science, 2829-511 Almada, Portugal"}]},{"given":"Marta","family":"Guimar\u00e3es","sequence":"additional","affiliation":[{"name":"UMIB\u2014Unit for Multidisciplinary Research in Biomedicine, ICBAS\u2014School of Medicine and Biomedical Sciences, Universidade do Porto, Rua Jorge Viterbo Ferreira 228, 4050-313 Porto, Portugal"},{"name":"ITR\u2014Laboratory of Integrative and Translocation Research in Population Health, Rua das Taipas 135, 4050-600 Porto, Portugal"}]},{"given":"H\u00e9lder","family":"Coelho","sequence":"additional","affiliation":[{"name":"Pathology Department, Hospital Garcia de Orta, 2805-267 Almada, Portugal"}]},{"given":"Ricardo","family":"Carregosa","sequence":"additional","affiliation":[{"name":"Cmicros\u2014Centro de Microscopia Eletr\u00f3nica e Histopatologia, CiiEM\u2014Centro de Investiga\u00e7\u00e3o Interdisciplinar Egas Moniz, 2829-511 Almada, Portugal"}]},{"given":"C\u00e1tia","family":"Oliveira","sequence":"additional","affiliation":[{"name":"Gastroenterology Department, GENE\u2014Artificial Feeding Team, Hospital Garcia de Orta, 2805-267 Almada, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6947-4560","authenticated-orcid":false,"given":"Sofia S.","family":"Pereira","sequence":"additional","affiliation":[{"name":"UMIB\u2014Unit for Multidisciplinary Research in Biomedicine, ICBAS\u2014School of Medicine and Biomedical Sciences, Universidade do Porto, Rua Jorge Viterbo Ferreira 228, 4050-313 Porto, Portugal"},{"name":"ITR\u2014Laboratory of Integrative and Translocation Research in Population Health, Rua das Taipas 135, 4050-600 Porto, Portugal"}]},{"given":"Ant\u00f3nio","family":"Alves de Matos","sequence":"additional","affiliation":[{"name":"Cmicros\u2014Centro de Microscopia Eletr\u00f3nica e Histopatologia, CiiEM\u2014Centro de Investiga\u00e7\u00e3o Interdisciplinar Egas Moniz, 2829-511 Almada, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6477-7028","authenticated-orcid":false,"given":"Jorge","family":"Fonseca","sequence":"additional","affiliation":[{"name":"Gastroenterology Department, GENE\u2014Artificial Feeding Team, Hospital Garcia de Orta, 2805-267 Almada, Portugal"},{"name":"ICBAS-UP\u2014Instituto de Ci\u00eancias Biom\u00e9dicas Abel Salazar, Universidade do Porto, 4050-313 Porto, Portugal"},{"name":"PaMNEC\u2014Grupo de Patologia M\u00e9dica, Nutri\u00e7\u00e3o e Estudos Cl\u00ednicos, Egas Moniz Center for Interdisciplinary Research (CiiEM), Egas Moniz School of Health and Science, 2829-511 Almada, Portugal"}]}],"member":"1968","published-online":{"date-parts":[[2023,12,30]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"105","DOI":"10.1159\/000460831","article-title":"The European Section and Board of Gastroenterology and Hepatology: What\u2019s new?","volume":"24","year":"2017","journal-title":"GE Port. J. Gastroenterol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1270","DOI":"10.1097\/MEG.0000000000001202","article-title":"Refeeding syndrome in the gastroenterology practice how concerned should we be?","volume":"30","author":"Nunes","year":"2018","journal-title":"Eur. J. Gastroenterol. Hepatol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1448","DOI":"10.1016\/j.nut.2014.03.026","article-title":"Refeeding syndrome problems with definition and management","volume":"30","author":"Crook","year":"2014","journal-title":"Nutrition"},{"key":"ref_4","first-page":"178","article-title":"Parenteral Nutrition Safety and Clinical Practice Committees, American Society for Parenteral and Enteral Nutrition. ASPEN Consensus Recommendations for Refeeding Syndrome","volume":"35","author":"Seres","year":"2020","journal-title":"Nutr. Clin. Pract."},{"key":"ref_5","unstructured":"National Institute for Health and Clinical Excellence (2006). Nutrition Support in Adults: Oral Nutrition Support, Enteral Tube Feeding and Parenteral Nutrition, National Institute for Health and Clinical Excellence. Available online: www.nice.org.uk\/page.aspx?o=cg032."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"3688","DOI":"10.1016\/j.clnu.2021.04.023","article-title":"The incidence of the refeeding syndrome. A systematic review and meta-analyses of literature","volume":"40","author":"Cioffi","year":"2021","journal-title":"Clin. Nutr."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"151","DOI":"10.1016\/j.nut.2016.05.016","article-title":"Revisiting the refeeding syndrome: Results of a systematic review","volume":"35","author":"Friedli","year":"2017","journal-title":"Nutrition"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"679","DOI":"10.1002\/ncp.10559","article-title":"Refeeding Hypophosphatemia in Patients Receiving Parenteral Nutrition: Prevalence, Risk Factors, and Predicting Its Occurrence","volume":"36","author":"Wong","year":"2021","journal-title":"Nutr. Clin. Pract."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"81","DOI":"10.1055\/a-1303-7449","article-title":"Endoscopic management of enteral tubes in adult patients\u2014Part 1: Definitions and indications. European Society of Gastrointestinal Endoscopy (ESGE) Guideline","volume":"53","author":"Arvanitakis","year":"2021","journal-title":"Endoscopy"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"178","DOI":"10.1055\/a-1331-8080","article-title":"Endoscopic management of enteral tubes in adult patients\u2014Part 2: Peri- and post-procedural management. European Society of Gastrointestinal Endoscopy (ESGE) Guideline","volume":"53","author":"Gkolfakis","year":"2021","journal-title":"Endoscopy"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"561","DOI":"10.20960\/nh.561","article-title":"Enteral feeding through endoscopic gastrostomy in amyotrophic lateral sclerosis patients","volume":"33","author":"Nunes","year":"2016","journal-title":"Nutr. Hosp."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"393","DOI":"10.1159\/000218162","article-title":"Mortality after nasogastric tube feeding initiation in long-term care elderly with oropharyngeal dysphagia -the contribution of refeeding syndrome","volume":"55","author":"Lubart","year":"2009","journal-title":"Gerontology"},{"key":"ref_13","first-page":"247","article-title":"Hypophosphatemia before endoscopic gastrostomy predicts higher mortality during the first week and first month post-gastrostomy a risk marker of refeeding syndrome in gastrostomy-fed patients","volume":"36","author":"Nunes","year":"2019","journal-title":"Nutr. Hosp."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"G916","DOI":"10.1152\/ajpgi.00429.2009","article-title":"Fasting-induced intestinal apoptosis is mediated by inducible nitric oxide synthase and interferon-{gamma} in rat","volume":"298","author":"Ito","year":"2010","journal-title":"Am. J. Physiol. Gastrointest. Liver Physiol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"765","DOI":"10.1023\/A:1022849112100","article-title":"Effects of incremental starvation on gut mucosa","volume":"48","author":"Chappell","year":"2003","journal-title":"Dig. Dis. Sci."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"323","DOI":"10.1007\/s00424-007-0289-0","article-title":"Morphological changes of the rat intestinal lining in relation to body stores depletion during fasting and after refeeding","volume":"455","author":"Habold","year":"2007","journal-title":"Pflug. Arch."},{"key":"ref_17","first-page":"790","article-title":"Effect of fasting and refeeding on the adaptation of the small intestine in rats. A model for physiopathologic studies","volume":"9","author":"Gorostiza","year":"1985","journal-title":"Gastroenterol. Clin. Biol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"209","DOI":"10.1016\/j.jss.2010.03.056","article-title":"Proximal gut mucosal epithelial homeostasis in aged IL-1 type I receptor knockout mice after starvation","volume":"169","author":"Song","year":"2011","journal-title":"J. Surg. Res."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1158","DOI":"10.1023\/A:1015019030514","article-title":"Morphometric and biomechanical intestinal remodeling induced by fasting in rats","volume":"47","author":"Dou","year":"2002","journal-title":"Dig. Dis. Sci."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"311","DOI":"10.1177\/0148607116686293","article-title":"To Create a Consensus on Malnutrition Diagnostic Criteria","volume":"41","author":"Cederholm","year":"2017","journal-title":"JPEN J. Parenter. Enter. Nutr."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"947","DOI":"10.1055\/a-1547-2282","article-title":"Endoscopy in patients on antiplatelet or anticoagulant therapy: British Society of Gastroenterology (BSG) and European Society of Gastrointestinal Endoscopy (ESGE) guideline update","volume":"53","author":"Veitch","year":"2021","journal-title":"Endoscopy"},{"key":"ref_22","unstructured":"Stewart, A., Marfell-Jones, M., and Olds, T. (2011). International Standards for Anthropometric Assessment, International Society for the Advancement of Kinanthropometry."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"307","DOI":"10.1016\/S0261-5614(03)00009-8","article-title":"A comparison of mid upper arm circumference, body mass index and weight loss as indices of undernutrition in acutely hospitalized patients","volume":"22","author":"Hennessy","year":"2003","journal-title":"Clin. Nutr."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"1584","DOI":"10.1016\/j.clnu.2017.08.011","article-title":"Mid upper arm circumference and Powell-Tuck and Hennessy\u2019s equation correlate with body mass index and can be used sequentially in gastrostomy fed patients","volume":"37","author":"Barosa","year":"2018","journal-title":"Clin. Nutr."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"468","DOI":"10.1016\/j.clnu.2021.10.018","article-title":"ESPEN practical guideline: Home enteral nutrition","volume":"41","author":"Bischoff","year":"2022","journal-title":"Clin. Nutr."},{"key":"ref_26","doi-asserted-by":"crossref","unstructured":"L\u00f3pez-G\u00f3mez, J.J., Ballesteros-Pomar, M.D., Torres-Torres, B., Pintor-De la Maza, B., Penacho-L\u00e1zaro, M.A., Palacio-Mures, J.M., Abreu-Pad\u00edn, C., Sanz-Gallego, I., and De Luis-Rom\u00e1n, D.A. (2021). Impact of Percutaneous Endoscopic Gastrostomy (PEG) on the Evolution of Disease in Patients with Amyotrophic Lateral Sclerosis (ALS). Nutrients, 13.","DOI":"10.3390\/nu13082765"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"292","DOI":"10.1097\/MPG.0000000000002381","article-title":"Correlates of Gut Function in Children Hospitalized for Severe Acute Malnutrition, a Cross-sectional Study in Uganda","volume":"69","author":"Lanyero","year":"2019","journal-title":"J. Pediatr. Gastroenterol. Nutr."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1181","DOI":"10.1136\/jcp.34.10.1181","article-title":"Measurements of intestinal villi non-specific and ulcer-associated duodenitis-correlation between area of microdissected villus and villus epithelial cell count","volume":"34","author":"Hasan","year":"1981","journal-title":"J. Clin. Pathol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"699","DOI":"10.1016\/j.bpj.2021.01.003","article-title":"Intestinal villus structure contributes to even shedding of epithelial cells","volume":"120","author":"Kai","year":"2021","journal-title":"Biophys. J."}],"container-title":["Nutrients"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2072-6643\/16\/1\/128\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T21:44:36Z","timestamp":1760132676000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2072-6643\/16\/1\/128"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,12,30]]},"references-count":29,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2024,1]]}},"alternative-id":["nu16010128"],"URL":"https:\/\/doi.org\/10.3390\/nu16010128","relation":{},"ISSN":["2072-6643"],"issn-type":[{"value":"2072-6643","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,12,30]]}}}