Gut microbiota-derived indole compounds attenuate metabolic dysfunction-associated steatotic liver disease by improving fat metabolism and inflammation

ABSTRACT

Metabolic dysfunction-associated steatotic liver disease (MASLD) is the most common chronic liver disease, and its prevalence has increased worldwide in recent years. Additionally, there is a close relationship between MASLD and gut microbiota-derived metabolites. However, the mechanisms of MASLD and its metabolites are still unclear. We demonstrated decreased indole-3-propionic acid (IPA) and indole-3-acetic acid (IAA) in the feces of patients with hepatic steatosis compared to healthy controls. Here, IPA and IAA administration ameliorated hepatic steatosis and inflammation in an animal model of WD-induced MASLD by suppressing the NF-κB signaling pathway through a reduction in endotoxin levels and inactivation of macrophages. Bifidobacterium bifidum metabolizes tryptophan to produce IAA, and B. bifidum effectively prevents hepatic steatosis and inflammation through the production of IAA. Our study demonstrates that IPA and IAA derived from the gut microbiota have novel preventive or therapeutic potential for MASLD treatment.

GRAPHICAL ABSTRACT

KEYWORDS:

• Metabolic dysfunction-associated steatotic liver disease
• indole
• metabolite
• gut microbiome
• Bifidobacterium

Disclosure statement

No potential conflict of interest was reported by the author(s).

Author contributions

K.T.S. and B.H.M. concepted and designed study. B.H.M. wrote the main manuscript text. B.H.M., H.G., G.H.K., J.J.J., S.S., R.G., S.M.W., K.K.O., S.J.Y., H.J.P., J.A.E., M.K.J., J.Y.H., and S.H.H. analyzed and interpreted data. K.T.S., S.D., N.S., and T.P. drafted and revised the manuscript. All authors contributed to manuscript revision, and read and approved the submitted version.

Availability of data and materials

All data are available in manuscript and supplementary file.

Ethical approval statement

The animals received humane care and all procedures were performed in accordance with National Institutes of Health Guidelines for the Care and Use of Laboratory Animals. This project followed the ethics of the 1975 Helsinki Declaration, as reflected by a prior approval by the institutional review board for human research in hospitals (2016–134). Informed consent was obtained from all participants. All authors had access to the study data and reviewed and approved the final manuscript.

Supplementary material

Supplemental data for this article can be accessed online at https://doi.org/10.1080/19490976.2024.2307568

Additional information

Funding

This research was supported by Hallym University Research Fund, the Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education, Science and Technology (NRF-2020R1A6A1A03043026), and Korea Institute for Advancement of Technology (P0020622).