Potential therapeutic implications of histidine catabolism by the gut microbiota in NAFLD patients with morbid obesity
Author(s)
Quesada-Vázquez, Sergio
Castells-Nobau, Anna
Latorre, Jèssica
Oliveras-Cañellas, Núria
Puig-Parnau, Irene
Type
Journal Article
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.
Date Issued
2023-12-19
Date Acceptance
2023-11-22
Citation
Cell Reports Medicine, 2023, 4 (12)
ISSN
2666-3791
Publisher
Elsevier
Journal / Book Title
Cell Reports Medicine
Volume
4
Issue
12
Copyright Statement
© 2023 The Authors. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
Identifier
https://www.ncbi.nlm.nih.gov/pubmed/38118419
Subjects
Animals
Diet, High-Fat
Gastrointestinal Microbiome
Histidine
Humans
Mice
Non-alcoholic Fatty Liver Disease
Obesity, Morbid
Rats
amino acids
dysbiosis
hepatic disease
histidine
Hut operon
NAFLD
omics
Proteobacteria
Publication Status
Published
Coverage Spatial
United States
Article Number
101341
Date Publish Online
2023-12-19