ORIGINAL RESEARCH article
Front. Cell Dev. Biol.
Sec. Molecular and Cellular Pathology
This article is part of the Research TopicIntegrative Omics for Insights into Human Disease Mechanisms and Therapeutic PotentialsView all 7 articles
Fecal microbiota transplantation alleviates steatosis and inflammation in high-fat and high-sugar diet-induced fatty liver in mice
Provisionally accepted
- 1Ningbo Hangzhou Bay Hospital (Ningbo Branch of Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai), Ningbo, China
- 2The Affiliated Yanming Hospital of Ningbo University, Ningbo, China
- 3The Affiliated Lihuili Hospital, Ningbo University, Ningbo, China
Select one of your emails
You have multiple emails registered with Frontiers:
Notify me on publication
Please enter your email address:
If you already have an account, please login
You don't have a Frontiers account ? You can register here
Aim To investigate whether fecal microbiota transplantation (FMT) could alleviate high-fat and high-sugar (HFCS) diet-induced metabolic dysfunction-associated fatty liver disease (MAFLD) in mice and explore potential mechanisms underlying gut microbiota modulation. Methods A MAFLD mouse model was established by feeding mice a HFCS diet for 20 weeks, followed by an 8-week intervention with FMT or saline, continuing for a total of 28 weeks. Gut microbiota composition, serum biochemical markers, liver histopathology, and inflammatory cytokine expression were evaluated. Results The HFCS diet induced significant changes in gut microbiota, including increased Firmicutes and decreased Bacteroidetes and Bifidobacterium. FMT partially restored microbiota composition to resemble that of control mice. Mice receiving FMT showed reduced body weight and a consistent trend toward improvement in serum alanine transaminase (ALT) and total cholesterol (TC) levels, although these changes did not reach statistical significance. Liver histology showed amelioration of steatosis and inflammation, as evidenced by reduced MAFLD activity score (NAS) and decreased intrahepatic expression of IL-1β and IL-17α mRNA. To further explore potential mechanisms, we analyzed a public liver transcriptomic dataset (GSE151220) involving FMT from dysbiotic donors. Differentially expressed genes were enriched in lipid metabolism and extracellular matrix (ECM)-related pathways, processes known to be involved in MAFLD progression. Conclusions These results suggest that FMT is associated with modulation of the gut–liver axis and partial alleviation of HFCS-induced MAFLD features in mice. FMT may serve as a potential adjunctive strategy for managing MAFLD.
Keywords: fecal microbiota transplantation, Gut-liver axis, high-fat and high-sugar diet, MAFLD, MASH
Received: 11 Oct 2025; Accepted: 09 Feb 2026.
Copyright: © 2026 Mi, Guo, Zheng and Ye. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Hua Ye
Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.