Partially hydrolyzed guar gum attenuates non-alcoholic fatty liver disease in mice through the gut-liver axis
| Autor: | Yuji Naito, Tomohiro Ueda, Katsura Mizushima, Kazuhiro Kamada, Tsutomu Okubo, Takeshi Ishikawa, Kazuhiro Katada, Osamu Handa, Takaya Iida, Yasuki Higashimura, Mayuko Morita, Yoshito Itoh, Shun Takayama, Zenta Yasukawa, Tetsuya Okayama, Kazuhiko Uchiyama, Tomohisa Takagi |
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| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
Male
medicine.medical_specialty Gut-liver axis Gut flora Chronic liver disease digestive system Galactans Butyric acid Mannans chemistry.chemical_compound Short-chain fatty acids Mice Partially hydrolyzed guar gum Non-alcoholic Fatty Liver Disease Internal medicine Plant Gums medicine Animals chemistry.chemical_classification Intestinal barrier integrity Intestinal permeability biology Triglyceride Fatty acid metabolism Chemistry Microbiota Fatty liver Gastroenterology Fatty acid General Medicine Basic Study biology.organism_classification medicine.disease Mice Inbred C57BL Endocrinology Liver |
| Zdroj: | World Journal of Gastroenterology |
| ISSN: | 2219-2840 1007-9327 |
| Popis: | Background The gut-liver axis has attracted much interest in the context of chronic liver disease pathogenesis. Prebiotics such as dietary fibers were shown to attenuate non-alcoholic fatty liver disease (NAFLD) by modulating gut microbiota. Partially hydrolyzed guar gum (PHGG), a water-soluble dietary fiber, has been reported to alleviate the symptoms of various intestinal diseases and metabolic syndromes. However, its effects on NAFLD remain to be fully elucidated. Aim To determine whether treatment with PHGG attenuates NAFLD development in mice through the gut-liver axis. Methods Seven-week-old male C57BL/6J mice with increased intestinal permeability were fed a control or atherogenic (Ath) diet (a mouse model of NAFLD) for 8 wk, with or without 5% PHGG. Increased intestinal permeability was induced through chronic intermittent administration of low-dose dextran sulfate sodium. Body weight, liver weight, macroscopic findings in the liver, blood biochemistry [aspartate aminotransferase (AST) and alanine aminotransferase (ALT), total cholesterol, triglyceride, free fatty acids, and glucose levels], liver histology, myeloperoxidase activity in liver tissue, mRNA expression in the liver and intestine, serum endotoxin levels in the portal vein, intestinal permeability, and microbiota and short-chain fatty acid (SCFA) profiles in the cecal samples were investigated. Results Mice with increased intestinal permeability subjected to the Ath diet showed significantly increased serum AST and ALT levels, liver fat accumulation, liver inflammatory (tumor necrosis factor-α and monocyte chemotactic protein-1) and fibrogenic (collagen 1a1 and α smooth muscle actin) marker levels, and liver myeloperoxidase activity, which were significantly attenuated by PHGG treatment. Furthermore, the Ath diet combined with increased intestinal permeability resulted in elevated portal endotoxin levels and activated toll-like receptor (TLR) 4 and TLR9 expression, confirming that intestinal permeability was significantly elevated, as observed by evaluating the lumen-to-blood clearance of fluorescein isothiocyanate-conjugated dextran. PHGG treatment did not affect fatty acid metabolism in the liver. However, it decreased lipopolysaccharide signaling through the gut-liver axis. In addition, it significantly increased the abundance of cecal Bacteroides and Clostridium subcluster XIVa. Treatment with PHGG markedly increased the levels of SCFAs, particularly, butyric acid, acetic acid, propionic acid, and formic acid, in the cecal samples. Conclusion PHGG partially prevented NAFLD development in mice through the gut-liver axis by modulating microbiota and downstream SCFA profiles. |
| Databáze: | OpenAIRE |
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