Microbiota Dysbiosis and Gut Barrier Dysfunction Associated with Non-Alcoholic Fatty Liver Disease Are Modulated by a Specific Metabolic Cofactors' Combination.
SCFAs
gut microbiota
gut-liver axis
intestinal permeability
metabolic disease
Journal
International journal of molecular sciences
ISSN: 1422-0067
Titre abrégé: Int J Mol Sci
Pays: Switzerland
ID NLM: 101092791
Informations de publication
Date de publication:
08 Nov 2022
08 Nov 2022
Historique:
received:
30
09
2022
revised:
31
10
2022
accepted:
04
11
2022
entrez:
26
11
2022
pubmed:
27
11
2022
medline:
30
11
2022
Statut:
epublish
Résumé
The gut is a selective barrier that not only allows the translocation of nutrients from food, but also microbe-derived metabolites to the systemic circulation that flows through the liver. Microbiota dysbiosis occurs when energy imbalances appear due to an unhealthy diet and a sedentary lifestyle. Dysbiosis has a critical impact on increasing intestinal permeability and epithelial barrier deterioration, contributing to bacterial and antigen translocation to the liver, triggering non-alcoholic fatty liver disease (NAFLD) progression. In this study, the potential therapeutic/beneficial effects of a combination of metabolic cofactors (a multi-ingredient; MI) (betaine, N-acetylcysteine, L-carnitine, and nicotinamide riboside) against NAFLD were evaluated. In addition, we investigated the effects of this metabolic cofactors' combination as a modulator of other players of the gut-liver axis during the disease, including gut barrier dysfunction and microbiota dysbiosis. Diet-induced NAFLD mice were distributed into two groups, treated with the vehicle (NAFLD group) or with a combination of metabolic cofactors (NAFLD-MI group), and small intestines were harvested from all animals for histological, molecular, and omics analysis. The MI treatment ameliorated gut morphological changes, decreased gut barrier permeability, and reduced gene expression of some proinflammatory cytokines. Moreover, epithelial cell proliferation and the number of goblet cells were increased after MI supplementation. In addition, supplementation with the MI combination promoted changes in the intestinal microbiota composition and diversity, as well as modulating short-chain fatty acids (SCFAs) concentrations in feces. Taken together, this specific combination of metabolic cofactors can reverse gut barrier disruption and microbiota dysbiosis contributing to the amelioration of NAFLD progression by modulating key players of the gut-liver axis.
Identifiants
pubmed: 36430154
pii: ijms232213675
doi: 10.3390/ijms232213675
pmc: PMC9692973
pii:
doi:
Substances chimiques
Fatty Acids, Volatile
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Subventions
Organisme : Biotechnology and Biological Sciences Research Council
ID : BB/CCG1860/1
Pays : United Kingdom
Organisme : Biotechnology and Biological Sciences Research Council
ID : BB/R012490/1
Pays : United Kingdom
Organisme : Biotechnology and Biological Sciences Research Council
ID : BBS/E/F/00044509
Pays : United Kingdom
Organisme : Biotechnology and Biological Sciences Research Council
ID : BB/R012512/1 - BBS/E/F/000PR10347
Pays : United Kingdom
Organisme : Biotechnology and Biological Sciences Research Council
ID : BBS/E/F/000PR10355
Pays : United Kingdom
Organisme : European Research Council
ID : erc-stg-948219.EPYC
Pays : International
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