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Quesada-Vázquez, Sergio, Castells-Nobau, Anna, Latorre, Jèssica, Oliveras-Cañellas, Núria, Puig-Parnau, Irene, Tejera, Noemi, Tobajas, Yaiza, Baudin, Julio, Hildebrand, Falk, Beraza, Naiara 
ORCID: https://orcid.org/0000-0003-0718-0940, Burcelin, Rémy, Martinez-Gili, Laura, Chilloux, Julien, Dumas, Marc-Emmanuel, Federici, Massimo, Hoyles, Lesley, Caimari, Antoni, Bas, Josep M. del, Escoté, Xavier, Fernández-Real, José-Manuel and Mayneris-Perxachs, Jordi
(2023)
Potential therapeutic implications of histidine catabolism by the gut microbiota in NAFLD patients with morbid obesity.
Cell Reports Medicine, 4 (12).
ISSN 2666-3791
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Abstract
The gut microbiota contributes to the pathophysiology of non-alcoholic fatty liver disease (NAFLD). Histidine is a key energy source for the microbiota, scavenging it from the host. Its role in NAFLD is poorly known. Plasma metabolomics, liver transcriptomics, and fecal metagenomics were performed in three human cohorts coupled with hepatocyte, rodent, and Drosophila models. Machine learning analyses identified plasma histidine as being strongly inversely associated with steatosis and linked to a hepatic transcriptomic signature involved in insulin signaling, inflammation, and trace amine-associated receptor 1. Circulating histidine was inversely associated with Proteobacteria and positively with bacteria lacking the histidine utilization (Hut) system. Histidine supplementation improved NAFLD in different animal models (diet-induced NAFLD in mouse and flies, ob/ob mouse, and ovariectomized rats) and reduced de novo lipogenesis. Fecal microbiota transplantation (FMT) from low-histidine donors and mono-colonization of germ-free flies with Enterobacter cloacae increased triglyceride accumulation and reduced histidine content. The interplay among microbiota, histidine catabolism, and NAFLD opens therapeutic opportunities.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | hut operon,nafld,proteobacteria,amino acids,dysbiosis,hepatic disease,histidine,omics,general biochemistry,genetics and molecular biology,sdg 3 - good health and well-being ,/dk/atira/pure/subjectarea/asjc/1300/1300 |
| Faculty \ School: | Faculty of Science > School of Biological Sciences |
| UEA Research Groups: | Faculty of Medicine and Health Sciences > Research Centres > Norwich Institute for Healthy Aging |
| Related URLs: | |
| Depositing User: | LivePure Connector |
| Date Deposited: | 05 Aug 2026 08:33 |
| Last Modified: | 10 Aug 2026 22:52 |
| URI: | https://ueaeprints.uea.ac.uk/id/eprint/103999 |
| DOI: | 10.1016/j.xcrm.2023.101341 |
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