Published online May 14, 2021. doi: 10.3748/wjg.v27.i18.2160
Peer-review started: February 6, 2021
First decision: February 27, 2021
Revised: March 12, 2021
Accepted: April 21, 2021
Article in press: April 21, 2021
Published online: May 14, 2021
Non-alcoholic fatty liver disease (NAFLD) is caused by a variety of pathogenesis, and may involve the gut-liver axis, which has attracted much attention. Prebiotics such as dietary fibers were shown to attenuate NAFLD by modulating gut microbiota. Partially hydrolyzed guar gum (PHGG), a water-soluble dietary fiber, is associated with alteration of gut microbiota and the production of short-chain fatty acids (SCFAs), and has been reported to alleviate the symptoms of various intestinal diseases and metabolic syndrome.
PHGG should exert beneficial health effects on the host through alterations to the gut microbiota and SCFA production. However, its effects on NAFLD remain to be fully elucidated.
The present study aimed to determine whether treatment with PHGG attenuates NAFLD development in mice through the gut-liver axis.
Male C57BL/6J mice with increased intestinal permeability by chronic intermittent administration of low-dose dextran sulfate sodium were fed a control or atherogenic (Ath) diet (a mouse model of NAFLD) for 8 wk, with or without 5% PHGG. Body weight, liver weight, macroscopic findings in the liver, blood biochemistry, 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 SCFA profiles in the cecal samples were investigated.
Mice subjected to a Ath diet with increased intestinal permeability showed significantly increased serum aspartate aminotransferase and alanine aminotransferase 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. Moreover, increased intestinal permeability in combination with the Ath diet resulted in increased portal endotoxin levels and activated toll-like receptor (TLR) 4 and TLR9 expression. PHGG administration did not affect fatty acid metabolism in the liver, but decreased lipopolysaccharide signaling through the gut-liver axis. The administration of PHGG altered the cecal bacteria profiles and significantly increased the 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.
Treatment with PHGG attenuated NAFLD development in mice through the gut-liver axis by modulating microbiota and downstream SCFA profiles.
By indicating that PHGG administration inhibits NAFLD development through the gut-liver axis, the present study showed a possible treatment strategy of NAFLD in humans.