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Dietary anthocyanins alleviates age-dependent hepatic steatosis by expanding Limosilactobacillus reuteri and modulating gut microbiota–bile acid–hepatic FXR signaling

Chen, Shen ; Wan, Chun ; Yu, Chao ; Shen, Tianran ; Zhang, Haoyang LU orcid ; Xiao, Jinghe ; You, Yiran ; Shen, Xinxin ; Li, Jie and Ling, Wenhua , et al. (2026) In Hepatology
Abstract
Background and Aims:
Metabolic dysfunction–associated steatotic liver disease (MASLD) is increasingly prevalent in aging populations. Dietary anthocyanin has been shown to exert metabolic benefits in aging and age-associated metabolic disorders. However, its role in protecting against age-dependent hepatic steatosis and the underlying mechanisms remain poorly defined.

Approach and Results:
In 18-month-old mice, dietary cyanidin-3-O-β-glucoside (Cy-3-G) markedly reduced hepatic triglyceride accumulation and improved serum liver enzyme levels without altering systemic glucose metabolism, body composition, or muscle function. Transcriptomic and pathway analyses identified hepatic farnesoid X receptor (FXR) signaling as the... (More)
Background and Aims:
Metabolic dysfunction–associated steatotic liver disease (MASLD) is increasingly prevalent in aging populations. Dietary anthocyanin has been shown to exert metabolic benefits in aging and age-associated metabolic disorders. However, its role in protecting against age-dependent hepatic steatosis and the underlying mechanisms remain poorly defined.

Approach and Results:
In 18-month-old mice, dietary cyanidin-3-O-β-glucoside (Cy-3-G) markedly reduced hepatic triglyceride accumulation and improved serum liver enzyme levels without altering systemic glucose metabolism, body composition, or muscle function. Transcriptomic and pathway analyses identified hepatic farnesoid X receptor (FXR) signaling as the primary mediator of Cy-3-G–induced improvements in lipid metabolism. Studies in hepatocyte-specific FXR knockout mice confirmed that this pathway is essential, while in vitro assays showed that Cy-3-G does not directly activate FXR in hepatocytes, underscoring the importance of microbiota-derived signals. Notably, Limosilactobacillus reuteri was identified as a key bacterium expanded by Cy-3-G, which increased bile salt hydrolase activity and promoted the breakdown of FXR-inhibitory tauro-β-MCA. Fecal microbiota transfer, synthetic community cultures, and direct L. reuteri supplementation further validated its causal role in lowering tauro-β-MCA and improving hepatic steatosis.

Conclusions:
Cy-3-G alleviates age-dependent hepatic steatosis by selectively promoting L. reuteri expansion and reshaping bile acid composition to activate hepatic FXR signaling. These findings identify a gut microbiota–mediated mechanism by which a dietary anthocyanin mitigates age-related MASLD. (Less)
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publishing date
type
Contribution to journal
publication status
epub
in
Hepatology
publisher
John Wiley & Sons Inc.
external identifiers
  • pmid:41746339
ISSN
1527-3350
DOI
10.1097/HEP.0000000000001721
language
English
LU publication?
no
id
8228a743-54fe-49b2-9ce7-c060b9cc0e9a
date added to LUP
2026-03-03 22:24:43
date last changed
2026-03-04 07:48:35
@article{8228a743-54fe-49b2-9ce7-c060b9cc0e9a,
  abstract     = {{Background and Aims: <br/>Metabolic dysfunction–associated steatotic liver disease (MASLD) is increasingly prevalent in aging populations. Dietary anthocyanin has been shown to exert metabolic benefits in aging and age-associated metabolic disorders. However, its role in protecting against age-dependent hepatic steatosis and the underlying mechanisms remain poorly defined.<br/><br/>Approach and Results: <br/>In 18-month-old mice, dietary cyanidin-3-O-β-glucoside (Cy-3-G) markedly reduced hepatic triglyceride accumulation and improved serum liver enzyme levels without altering systemic glucose metabolism, body composition, or muscle function. Transcriptomic and pathway analyses identified hepatic farnesoid X receptor (FXR) signaling as the primary mediator of Cy-3-G–induced improvements in lipid metabolism. Studies in hepatocyte-specific FXR knockout mice confirmed that this pathway is essential, while in vitro assays showed that Cy-3-G does not directly activate FXR in hepatocytes, underscoring the importance of microbiota-derived signals. Notably, Limosilactobacillus reuteri was identified as a key bacterium expanded by Cy-3-G, which increased bile salt hydrolase activity and promoted the breakdown of FXR-inhibitory tauro-β-MCA. Fecal microbiota transfer, synthetic community cultures, and direct L. reuteri supplementation further validated its causal role in lowering tauro-β-MCA and improving hepatic steatosis.<br/><br/>Conclusions: <br/>Cy-3-G alleviates age-dependent hepatic steatosis by selectively promoting L. reuteri expansion and reshaping bile acid composition to activate hepatic FXR signaling. These findings identify a gut microbiota–mediated mechanism by which a dietary anthocyanin mitigates age-related MASLD.}},
  author       = {{Chen, Shen and Wan, Chun and Yu, Chao and Shen, Tianran and Zhang, Haoyang and Xiao, Jinghe and You, Yiran and Shen, Xinxin and Li, Jie and Ling, Wenhua and Huang, Rong and Xue, Hongliang and Chen, Xu}},
  issn         = {{1527-3350}},
  language     = {{eng}},
  publisher    = {{John Wiley & Sons Inc.}},
  series       = {{Hepatology}},
  title        = {{Dietary anthocyanins alleviates age-dependent hepatic steatosis by expanding Limosilactobacillus reuteri and modulating gut microbiota–bile acid–hepatic FXR signaling}},
  url          = {{http://dx.doi.org/10.1097/HEP.0000000000001721}},
  doi          = {{10.1097/HEP.0000000000001721}},
  year         = {{2026}},
}