Gut Microbiome

Integrative multi-omics reveals that Pueraria thomsonii Radix alleviates dyslipidemia by remodeling gut microbiota and regulating arachidonic acid metabolism.

TL;DR

PTR may ameliorate dyslipidemia through coordinated modulation of the gut microbiota and arachidonic acid metabolic network, with the hepatic AMPK signaling pathway potentially involved in this regulatory process.

Key Findings

Pueraria thomsonii Radix (PTR) significantly ameliorated dyslipidemia in high-fat diet-fed rats as evidenced by improved serum lipid profiles.

  • A high-fat-diet rat model was used to assess pharmacodynamic endpoints including serum lipid panel
  • PTR treatment resulted in improved serum lipid profiles compared to high-fat diet controls
  • Reduced ALT/AST levels were observed following PTR treatment, indicating reduced liver injury
  • Alleviated hepatic steatosis and inflammation were confirmed by histopathological examination

Integrated metabolomic analysis across both rats and patients revealed that restored metabolic pathways were primarily concentrated in arachidonic acid and unsaturated fatty acid metabolism.

  • Untargeted plasma metabolomics was performed in both rats and human patients
  • Cross-species metabolomic comparison identified converging pathway changes
  • Arachidonic acid metabolism and unsaturated fatty acid metabolism were the primary enriched pathways
  • Multivariate models were cross-validated and FDR-controlled to ensure statistical rigor

PTR remodeled gut microbial taxa that were correlated with arachidonic acid-related lipid metabolism.

  • Rat fecal 16S rRNA gene sequencing was used to characterize gut microbiota composition
  • Specific microbial taxa were identified as being remodeled by PTR treatment
  • Multi-omics correlation analyses integrated metabolite-microbe-gene relationships
  • The remodeled microbial taxa showed correlation with arachidonic acid-related lipid metabolism pathways

Hepatic transcriptomics revealed that differentially expressed genes were functionally enriched in lipid oxidation and bioinformatically linked to the AMPK signaling pathway.

  • Hepatic transcriptomics data identified differentially expressed genes following PTR treatment
  • Differentially expressed genes were functionally enriched in biological processes such as lipid oxidation
  • Bioinformatic analysis linked these genes to the AMPK signaling pathway
  • The authors note that the direct mechanistic role of AMPK requires further experimental validation beyond the bioinformatic association

Chemical profiling by UPLC-Q-TOF-MS/MS characterized the active constituents and plasma exposure of PTR.

  • UPLC-Q-TOF-MS/MS was used for chemical profiling and plasma exposure characterization
  • This method identified the constituents of PTR that reached systemic circulation
  • PTR is described as a food-medicine herb widely used in China for metabolic complaints
  • The chemical profiling was used to establish the pharmacological basis of the observed effects

Multi-omics integration linked gut microbiota remodeling, arachidonic acid metabolic network modulation, and hepatic gene expression changes as coordinated mechanisms of PTR's anti-dyslipidemic effects.

  • Pathway and multi-omics correlation analyses integrated metabolite-microbe-gene relationships
  • Gut microbiota analysis, plasma metabolomics, and hepatic transcriptomics were jointly analyzed
  • The authors conclude PTR acts through 'coordinated modulation of the gut microbiota and arachidonic acid metabolic network'
  • Future investigations employing targeted lipid-omics, protein phosphorylation assays, and microbiota-transfer experiments are recommended to elucidate causal relationships

What This Means

This research examined how Pueraria thomsonii Radix (PTR), a traditional Chinese food-medicine herb known as 'Fen-ge,' may help treat abnormal blood fat levels (dyslipidemia). Researchers fed rats a high-fat diet to create a model of dyslipidemia, then treated them with PTR. They used multiple advanced analysis techniques — including chemical profiling of PTR's components, blood metabolite analysis in both rats and human patients, gut bacteria profiling, and liver gene expression analysis — to understand how PTR works at a molecular level. The study found that PTR improved blood lipid profiles, reduced liver injury markers, and reduced fatty liver disease signs in the treated rats. By comparing metabolite changes in both the rat model and human patients, the researchers identified that PTR's effects were most strongly associated with changes in arachidonic acid metabolism and unsaturated fatty acid processing. PTR also appeared to reshape the composition of gut bacteria in ways that correlated with these metabolic improvements. Analysis of liver gene activity suggested involvement of the AMPK signaling pathway, which is a well-known regulator of energy and fat metabolism, though the researchers caution this link is currently based on computational analysis and needs direct experimental confirmation. This research suggests that PTR may work through a coordinated, multi-system mechanism involving the gut microbiome and fat metabolism pathways rather than through a single target. The finding that similar metabolic pathway changes appeared in both animal models and human patients strengthens the translational relevance of the results. The authors call for follow-up studies using more targeted methods — including gut bacteria transplant experiments and direct protein activity measurements — to confirm whether these associations represent true cause-and-effect relationships.

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Citation

Yin D, Chen M, Chen X, Feng Y, Zhou X, Guan Y, et al.. (2026). Integrative multi-omics reveals that Pueraria thomsonii Radix alleviates dyslipidemia by remodeling gut microbiota and regulating arachidonic acid metabolism.. Journal of ethnopharmacology. https://doi.org/10.1016/j.jep.2026.121816