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. 2025 Apr 30;18(5):661.
doi: 10.3390/ph18050661.

Gut Microbiota-Targeted Intervention of Hyperlipidemia Using Monascus-Fermented Ginseng

Qing Zhou  1 , Cuiting Yang  2 , Mingyue Jia  2 , Qingsong Qu  1 , Xinhui Peng  1 , Weishuo Ren  1 , Guoqing Li  1 , Yueyang Xie  1 , Bingxuan Li  1 , Xinyuan Shi  1   3
Affiliations

Gut Microbiota-Targeted Intervention of Hyperlipidemia Using Monascus-Fermented Ginseng

Qing Zhou et al. Pharmaceuticals (Basel). .

Abstract

Background/Objectives: Hyperlipidemia (HLP) encompasses a spectrum of poorly understood lipid metabolism disorders that are frequently overlooked or misdiagnosed, potentially leading to multiple complications. While the gut microbiota has been implicated in HLP pathogenesis, the causal relationships and molecular mechanisms remain elusive. This study aimed to investigate the therapeutic mechanisms of Monascus-fermented ginseng (MFG) on HLP through gut microbiota modulation and explore treatment potential via fecal microbiota transplantation (FMT). Methods: The MFG-modulated gut microbiota was transplanted into HLP mice. Systemic evaluations, including serum biochemical parameter detection, histopathological section analysis, 16S rRNA sequencing, and fecal metabolomics, were conducted to assess therapeutic efficacy and identify associated metabolic pathways. Results: FMT significantly improved lipid profiles, reduced body weight, and attenuated hepatic lipid accumulation in HLP mice. Mechanistically, it enhanced cholesterol excretion and fatty acid β-oxidation while suppressing lipogenic regulators, concurrently promoting primary-to-secondary bile acid conversion. Gut microbiota analysis revealed that the MFG intervention effectively normalized the Firmicutes/Bacteroidetes ratio and enriched beneficial microbiota. Conclusions: These findings demonstrate FMT's therapeutic value in HLP management and provide new perspectives on utilizing fermented herbal medicines for metabolic disorders via gut microbiota reprogramming.

Keywords: fecal microbiota transplantation; fermentation; ginseng; gut microbiota; hyperlipidemia.

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Conflict of interest statement

The authors declare that they have no competing interests.

Figures

Figure 1
Figure 1
Effect of FMT on phenotype and biochemical indicator alterations: (A) body weight, (B) liver performance, (C) liver weight, (D) epididymal fat, (E) perirenal fat, (F) blood glucose, (G) serum ALT, (H) serum AST, (I) serum BUN, and (J) serum ALB. * p < 0.05; ** p < 0.01; *** p < 0.001.
Figure 2
Figure 2
Effects of FMT on lipid metabolism. (A–D) Serum lipid profile: (A) total cholesterol, (B) triglycerides, (C) low-density lipoprotein cholesterol, and (D) high-density lipoprotein cholesterol. (E–G) Hepatic histopathological analysis: (E) quantification of oil red O-stained lipid droplets, (F) representative microphotographs of oil red O, and (G) hematoxylin and eosin (E) staining of liver tissue. * p < 0.05; ** p < 0.01; *** p < 0.001.
Figure 3
Figure 3
Effects of FMT on hepatic gene expression profiles: (A) Hmgcr, (B) Srebp1c, (C) Cyp7a1, (D) Fxr, (E) Abca1, (F) Abcg1, (G) Npc1, (H) Srb1, (I) Ldlr, (J) Acat2, (K) Acc1, (L) Scd1, (M) Cd36, (N) Acox1, and (O) Cpt1a. * p < 0.05; ** p < 0.01; *** p < 0.001.
Figure 4
Figure 4
Effects of FMT on altered gut microbiota: (A) rarefaction curves, (B) Shannon curves, (C) Rank–Abundance curves, (D) ACE index, (E) Chao index, (F) Sobs index, (G) percent of community abundance on phylum level, and (H) percent of community abundance on family level.
Figure 5
Figure 5
Effects of FMT on SCFA contents: (A) acetic acid, (B) propionic acid, (C) butyric acid, (D) isobutyric acid, (E) valeric acid, (F) isovaleric acid, (G) hexanoic acid, and (H) isohexanoic acid. * p < 0.05; ** p < 0.01; *** p < 0.001.
Figure 6
Figure 6
Effects of FMT on regulation of BAs metabolism: (A) conjugated BAs in serum, (B) free BAs in serum, (C) primary BAs in serum, (D) secondary BAs in serum, (E) conjugated BAs in feces, (F) free BAs in feces, (G) primary BAs in feces, (H) secondary BAs in feces. * p < 0.05; ** p < 0.01; *** p < 0.001.
Figure 7
Figure 7
Heat map of BAs: (A) in serum and (B) in feces.
Figure 8
Figure 8
Animal experiment flow.
See this image and copyright information in PMC

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