Potential therapeutic implications of histidine catabolism by the gut microbiota in NAFLD patients with morbid obesity

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 i...

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Published in:Cell reports. Medicine 2023-12, Vol.4 (12), p.101341-101341, Article 101341
Main Authors: Quesada-Vázquez, Sergio, Castells-Nobau, Anna, Latorre, Jèssica, Oliveras-Cañellas, Núria, Puig-Parnau, Irene, Tejera, Noemi, Tobajas, Yaiza, Baudin, Julio, Hildebrand, Falk, Beraza, Naiara, Burcelin, Rémy, Martinez-Gili, Laura, Chilloux, Julien, Dumas, Marc-Emmanuel, Federici, Massimo, Hoyles, Lesley, Caimari, Antoni, Del Bas, Josep M, Escoté, Xavier, Fernández-Real, José-Manuel, Mayneris-Perxachs, Jordi
Format: Article
Language:English
Subjects:
Animals
Diet, High-Fat
Gastrointestinal Microbiome - physiology
Histidine - therapeutic use
Humans
Life Sciences
Mice
Non-alcoholic Fatty Liver Disease - drug therapy
Obesity, Morbid
Rats
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Summary: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.
ISSN:2666-3791
2666-3791
DOI:10.1016/j.xcrm.2023.101341