Basic Study
Copyright ©The Author(s) 2021. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. May 14, 2021; 27(18): 2160-2176
Published online May 14, 2021. doi: 10.3748/wjg.v27.i18.2160
Partially hydrolyzed guar gum attenuates non-alcoholic fatty liver disease in mice through the gut-liver axis
Shun Takayama, Kazuhiro Katada, Tomohisa Takagi, Takaya Iida, Tomohiro Ueda, Katsura Mizushima, Yasuki Higashimura, Mayuko Morita, Tetsuya Okayama, Kazuhiro Kamada, Kazuhiko Uchiyama, Osamu Handa, Takeshi Ishikawa, Zenta Yasukawa, Tsutomu Okubo, Yoshito Itoh, Yuji Naito
Shun Takayama, Kazuhiro Katada, Tomohisa Takagi, Takaya Iida, Tomohiro Ueda, Katsura Mizushima, Tetsuya Okayama, Kazuhiro Kamada, Kazuhiko Uchiyama, Takeshi Ishikawa, Yoshito Itoh, Yuji Naito, Department of Molecular Gastroenterology and Hepatology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto 602-8566, Japan
Tomohisa Takagi, Department of Medical Innovation and Translational Medical Science, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto 602-8566, Japan
Yasuki Higashimura, Department of Food Science, Ishikawa Prefectural University, Nonoichi 921-8836, Japan
Mayuko Morita, Department of Health Care Nutrition, Showa Gakuin Junior College, Ichikawa 272-0823, Japan
Osamu Handa, Division of Gastroenterology, Department of Internal Medicine, Kawasaki Medical School, Kurashiki 701-0192, Japan
Zenta Yasukawa, Tsutomu Okubo, Department of Nutrition, Taiyo Kagaku Co. Ltd, Yokkaichi 510-0844, Japan
Author contributions: Takayama S performed the research, analyzed the data, and wrote the manuscript; Katada K designed the research study, and wrote the manuscript; Higashimura Y performed the biostatistical analysis, and critically reviewed the manuscript; Takagi T, Iida T, Ueda T, Mizushima K, Morita M, Okayama T, Kamada K, Uchiyama K, Handa O, Ishikawa T, Yasukawa Z, Okubo T, Itoh Y, and Naito Y contributed to data collection and interpretation, and critically reviewed the manuscript; all authors approved the final version of the manuscript, and agree to be accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved.
Supported by Scientific Research (KAKENHI) (C), No. 25460958; Japan Society for the Promotion of Science, No. 20K11513; and Adaptable and Seamless Technology Transfer Program through target driven R&D from the Japan Agency for Medical Research and Development.
Institutional review board statement: At our institution, the attached “Institutional Animal Care and Use Committee Approval Form” also serves as the Institutional Review Board Approval Form. The study was reviewed and approved by the Institutional Review Board at Kyoto Prefectural University of Medicine.
Institutional animal care and use committee statement: All procedures involving animal subject is approved by the Animal Care Committee of the Kyoto Prefectural University of Medicine, Kyoto, Japan, No. M2020-126.
Conflict-of-interest statement: All authors have nothing to disclose.
Data sharing statement: No additional data are available.
ARRIVE guidelines statement: The authors have read the ARRIVE guidelines, and the manuscript was prepared and revised according to the ARRIVE guidelines.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See:
Corresponding author: Kazuhiro Katada, MD, PhD, Assistant Professor, Department of Molecular Gastroenterology and Hepatology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, 465 Kajii-cho, Kawaramachi-Hirokoji, Kamigyo-ku, Kyoto 602-8566, Japan.
Received: February 6, 2021
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
Research background

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.

Research motivation

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.

Research objectives

The present study aimed to determine whether treatment with PHGG attenuates NAFLD development in mice through the gut-liver axis.

Research methods

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.

Research results

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.

Research conclusions

Treatment with PHGG attenuated NAFLD development in mice through the gut-liver axis by modulating microbiota and downstream SCFA profiles.

Research perspectives

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.