Diet shapes the metabolite profile in the intact human ileum, which affects PYY release

Dagbasi, Aygul, Byrne, Claire, Blunt, Dominic, Serrano-Contreras, Jose Ivan, Becker, Georgia Franco, Blanco, Jesus Miguens, Camuzeaux, Stephane, Chambers, Edward, Danckert, Nathan, Edwards, Cathrina, Bernal, Andres, Garcia, Maria Valdivia, Hanyaloglu, Aylin, Holmes, Elaine, Ma, Yue, Marchesi, Julian, Martinez-Gili, Laura, Mendoza, Lilian, Tashkova, Martina, Perez-Moral, Natalia, Garcia-Perez, Isabel, Robles, Andres Castillo, Sands, Caroline, Wist, Julien, Murphy, Kevin G. and Frost, Gary (2024) Diet shapes the metabolite profile in the intact human ileum, which affects PYY release. Science Translational Medicine, 16 (752). ISSN 1946-6234

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Abstract

The human ileum contains a high density of enteroendocrine L-cells, which release the appetite-suppressing hormones glucagon-like peptide-1 (GLP-1) and peptide tyrosine tyrosine (PYY) in response to food intake. Recent evidence highlighted the potential role of food structures in PYY release, but the link between food structures, ileal metabolites, and appetite hormone release remains unclear owing to limited access to intact human ileum. In a randomized crossover trial (ISRCTN11327221; isrctn.com), we investigated the role of human ileum in GLP-1 and PYY release by giving healthy volunteers diets differing in fiber and food structure: high-fiber (intact or disrupted food structures) or low-fiber disrupted food structures. We used nasoenteric tubes to sample chyme from the intact distal ileum lumina of humans in the fasted state and every 60 min for 480 min postprandially. We demonstrate the highly dynamic, wide-ranging molecular environment of the ileum over time, with a substantial decrease in ileum bacterial numbers and bacterial metabolites after food intake. We also show that high-fiber diets, independent of food structure, increased PYY release compared with a low-fiber diet during 0 to 240 min postprandially. High-fiber diets also increased ileal stachyose, and a disrupted high-fiber diet increased certain ileal amino acids. Treatment of human ileal organoids with ileal fluids or an amino acid and stachyose mixture stimulated PYY expression in a similar profile to blood PYY concentrations, confirming the role of ileal metabolites in PYY release. Our study demonstrates the diet-induced changes over time in the metabolite environment of intact human ileum, which play a role in PYY release.

Item Type:	Article
Additional Information:	Funding: This independent research was funded by Biotechnology and Biological Sciences Research Council (BB/N016947/1), Nestle Research, and Sosei Heptares, and it was carried out at the NIH and Care Research (NIHR) Imperial Clinical Research Facility (CRF). The views expressed are those of the author(s) and not necessarily those of the Biotechnology and Biological Sciences Research Council, the NIHR, or the Department of Health and Social Care. The Section for Nutrition at Imperial College London is funded by grants from the UK Medical Research Council, Biotechnology and Biological Sciences Research Council, National Institute for Health and Care Research, and UKRI Innovate UK and is supported by the National Institute for Health and Care Research Imperial Biomedical Research Centre Funding Scheme. L.M.-G. is supported by the NIHR Imperial Biomedical Research Centre (BRC). This study was funded by UKRI BBSRC (BB/N016947/1; recipient, G.F.). The lipid analysis was funded by a British Nutrition Foundation Drummond Early Career Scientist Award 2022 (recipient, A.D.). The food microscopy studies were supported by the BBSRC Food Innovation and Health Institute Strategic Programme BB/R012512/1 and its constituent project BBS/E/F/000PR10345.
Uncontrolled Keywords:	medicine(all) ,/dk/atira/pure/subjectarea/asjc/2700
Faculty \ School:	Faculty of Science > School of Biological Sciences
Related URLs:	http://www.scopus.com/inward/record.url?...
Depositing User:	LivePure Connector
Date Deposited:	18 Feb 2025 10:30
Last Modified:	21 Feb 2025 09:30
URI:	https://ueaeprints.uea.ac.uk/id/eprint/98528
DOI:	10.1126/scitranslmed.adm8132

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