Phocaeicola vulgatus alleviates diet-induced metabolic dysfunction-associated steatotic liver disease progression by downregulating histone acetylation level via 3-HPAA

ABSTRACT

Diet-induced metabolic dysfunction-associated steatotic liver disease (MASLD) is a prevalent metabolic disorder with limited effective interventions available. A novel approach to address this issue is through gut microbiota-based therapy. In our study, we utilized multi-omics analysis to identify Phocaeicola vulgatus (P. vulgatus) as a potential probiotic for the treatment of MASLD. Our findings from murine models clearly illustrate that the supplementation of P. vulgatus mitigates the development of MASLD. This beneficial effect is partly attributed to the metabolite 3-Hydroxyphenylacetic acid (3-HPAA) produced by P. vulgatus, which reduces the acetylation levels of H3K27 and downregulates the transcription of Squalene Epoxidase (SQLE), a rate-limiting enzyme in steroid biosynthesis that promotes lipid accumulation in liver cells. This study underscores the significant role of P. vulgatus in the development of MASLD and the critical importance of its metabolite 3-HPAA in regulating lipid homeostasis. These findings offer a promising avenue for early intervention therapy in the context of MASLD.

KEYWORDS:

• Intestinal microbiology
• lipid metabolism
• fatty liver
• probiotics
• molecular mechanisms

Acknowledgments

We thank Xiaoli Hong and Chao Bi from the Core Facilities, Zhejiang University School of Medicine for their technical support. We also thank Wei Liu and Jiaqing Wang from Zhejiang Academy of Agricultural Sciences for their technical support.

Disclosure statement

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

Authors’ contributions

SX Jin and P Chen were involved in study design, performed experiments and drafted the manuscript; J Yang performed original draft and review & editing; DG Li, QM Xia, XL Liu and YF Tong performed animal experiments; WH Yu performed histological evaluation; YY Zhang performed original draft and review & editing; YL Li, YX Li, GQ Chen performed review & editing; XX Fan, H Lin designed, supervised the study and revised the manuscript.

Data availability material

The datasets analyzed in our study are openly available in figshare at 10.6084/m9.figshare.23622366.

Supplementary material

Supplemental data for this article can be accessed online at https://doi.org/10.1080/19490976.2024.2309683

Additional information

Funding

This work was supported by the National Natural Science Foundation of China [81874059 and 82102105]; Natural Science Foundation of Zhejiang Province [LQ22H160017, LQ21H030012]; Medical and Health Research Project of Zhejiang Province [2019325792].