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Castells-Nobau, A.* ; Moreno-Navarrete, J.M.* ; de la Vega-Correa, L.* ; Puig, I.* ; Federici, M.* ; Sun, J.* ; Burcelin, R.* ; Guzylack-Piriou, L.* ; Gourdy, P.* ; Cazals, L.* ; Arnoriaga-Rodríguez, M.* ; Fruhbeck, G.* ; Seoane, L.M.* ; López-Miranda, J.* ; Tinahones, F.J.* ; Dieguez, C.* ; Dumas, M.E.* ; Pérez-Brocal, V.* ; Moya, A.* ; Perakakis, N. ; Mingrone, G.* ; Bornstein, S.R. ; Rodriguez Hermosa, J.I.* ; Castro, E.* ; Fernández-Real, J.M.* ; Mayneris-Perxachs, J.*

Multiomics of the intestine-liver-adipose axis in multiple studies unveils a consistent link of the gut microbiota and the antiviral response with systemic glucose metabolism.

Gut, DOI: 10.1136/gutjnl-2024-332602 (2024)
Verlagsversion DOI PMC
Open Access Gold (Paid Option)
Creative Commons Lizenzvertrag
BACKGROUND: The microbiota is emerging as a key factor in the predisposition to insulin resistance and obesity. OBJECTIVE: To understand the interplay among gut microbiota and insulin sensitivity in multiple tissues. DESIGN: Integrative multiomics and multitissue approach across six studies, combining euglycaemic clamp measurements (used in four of the six studies) with other measurements of glucose metabolism and insulin resistance (glycated haemoglobin (HbA1c) and fasting glucose). RESULTS: Several genera and species from the Proteobacteria phylum were consistently negatively associated with insulin sensitivity in four studies (ADIPOINST, n=15; IRONMET, n=121, FLORINASH, n=67 and FLOROMIDIA, n=24). Transcriptomic analysis of the jejunum, ileum and colon revealed T cell-related signatures positively linked to insulin sensitivity. Proteobacteria in the ileum and colon were positively associated with HbA1c but negatively with the number of T cells. Jejunal deoxycholic acid was negatively associated with insulin sensitivity. Transcriptomics of subcutaneous adipose tissue (ADIPOMIT, n=740) and visceral adipose tissue (VAT) (ADIPOINST, n=29) revealed T cell-related signatures linked to HbA1c and insulin sensitivity, respectively. VAT Proteobacteria were negatively associated with insulin sensitivity. Multiomics and multitissue integration in the ADIPOINST and FLORINASH studies linked faecal Proteobacteria with jejunal and liver deoxycholic acid, as well as jejunal, VAT and liver transcriptomic signatures involved in the actin cytoskeleton, insulin and T cell signalling. Fasting glucose was consistently linked to interferon-induced genes and antiviral responses in the intestine and VAT. Studies in Drosophila melanogaster validated these human insulin sensitivity-associated changes. CONCLUSION: These data provide comprehensive insights into the microbiome-gut-adipose-liver axis and its impact on systemic insulin action, suggesting potential therapeutic targets.Cite Now.
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Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Korrespondenzautor
Schlagwörter Intestinal Bacteria ; Liver ; Obesity; Insulin-resistance; Obesity; Inflammation; Sensitivity; Improvement; Jejunum
ISSN (print) / ISBN 0017-5749
e-ISSN 1468-3288
Zeitschrift Gut (eGut)
Verlag BMJ Publishing Group
Verlagsort British Med Assoc House, Tavistock Square, London Wc1h 9jr, England
Nichtpatentliteratur Publikationen
Begutachtungsstatus Peer reviewed
Institut(e) Institute for Pancreatic Beta Cell Research (IPI)
Förderungen Site ULNE
Federation Francaise de Recherche en Diabetologie
Sara Borrell Program
Autonomous Community of Catalonia
Recovery, Transformation and Resilience Plan
European Union NextGenerationEU
Spanish Ministry of Science, Innovation and Universities
Generalitat de Catalunya
European Union NextGenerationEU/PRTR
MCIN/AEI
European Union
European Union/Plan de Recuperacion, Transformacion y Resiliencia
Instituto de Salud Carlos III
Fondation Francophone pour la Recherche sur le Diabete
FFD
European Metropolis of Lille
Hauts-de-France Regional Council
National Center for Precision Diabetic Medicine,
French National Research Agency
NIHR Imperial Biomedical Research Centre
Diabetes UK
GutsUK
Sanofi
Novo Nordisk
MSD
Lilly
AstraZeneca
Abbott
EU-FP7 FLORINASH