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Clin. Mol. Hepatol., Oct 27 2025, | https://doi.org/10.3350/cmh.2025.0475 Bacteroides eggerthii Ameliorates MASLD through Host-Microbe Signaling and Highlights 2-Hydroxyisocaproate as a Potential Effector

Jiyi Choi ^{1 2 †}, Moon Gyeong Yoon ^{1 †}, Se Ha Jang^{1 2}, Geum Ok Baek ¹, Hyun Sun Jung ¹, Na-Rae Lee ³, Choong Hwan Lee ³, Ji Eun Han¹, Jae Youn Cheong ¹, Jung Woo Eun ^{1 *}, Soon Sun Kim^{1 *}

¹Department of Gastroenterology, Ajou University School of Medicine, Suwon, South Korea.
²Department of Biomedical Sciences, Ajou University Graduate School of Medicine, Suwon, South Korea.
³MetaMass Corp., Seoul, South Korea.

^†These authors contributed equally
^*Corresponding authors: correspondence to Jung Woo Eun or Soon Sun Kim

Abstract

Background/Aims
Gut microbiome plays a pivotal role in metabolic dysfunction-associated steatotic liver disease (MASLD) pathogenesis, yet, associated functional mechanisms and host responses of specific microbial species remain insufficiently characterized. This study investigated the Bacteroides eggerthii therapeutic effects on MASLD by integrating multi-omics analysis and experimental validation in a Western diet-induced mouse model.

Methods
Candidate strains were identified using 16S rRNA gene sequencing of fecal samples from individuals with and without MASLD or obesity. B. eggerthii, a species significantly depleted in both groups, was selected for functional evaluation. Male C57BL/6J mice were fed a Western diet (WD) or WD supplemented with B. eggerthii (WD+B) for 12 weeks. Liver histology, serum biochemistry, fecal microbiome and metabolome profiling, and hepatic and intestinal transcriptomic analyses were performed. Anti-steatotic effects of B. eggerthii–derived metabolites were validated in vitro.

Results
Bacteroides eggerthii supplementation significantly improved liver weight, inflammation, fibrosis, and steatosis in WD+B group compared to WD alone. PICRUSt-based LEfSe analysis revealed choloylglycine hydrolase activity enrichment in gut microbiota, and strain-specific qPCR confirmed colonization in mouse colon. Integrated transcriptomic analyses revealed lipid and bile acid signaling pathway restoration, including CD36, FXR, and FGF15. Untargeted metabolomics identified elevated 2-hydroxyisocaproic acid (HICA) as a strain-derived metabolite in feces and B. eggerthii culture supernatants. In vitro, HICA significantly reduced lipid accumulation in free fatty acid-induced steatosis models.

Conclusion
Bacteroides eggerthii ameliorates MASLD via gut-liver axis modulation, including bile acid metabolism and hepatic lipid signaling. These underscore its therapeutic potential and highlight HICA as a novel microbiome-derived metabolite with anti-steatotic activity.

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