TCM-Derived Natural Compounds Targeting Gut Microbiota in MASLD: Gut–Liver Axis Mechanisms, Safety, and Translational Challenges
This structured narrative review maps proposed mechanisms of TCM monomers on the gut–liver axis in MASLD but does not establish clinical efficacy or causality — effect direction remains insufficient for clinical recommendation.
| Outcome | Grade | Direction | Effect | Studies |
|---|---|---|---|---|
| Hepatic steatosis | D | — Insufficient | not pooled; preclinical narrative only | — |
| Hepatic inflammation (ALT/AST, histology) | D | — Insufficient | not pooled; preclinical narrative only | — |
| Intestinal barrier integrity | D | — Insufficient | not pooled; preclinical narrative only | — |
| Gut microbiota diversity and composition | D | — Insufficient | not pooled; preclinical narrative only | — |
| Microbial metabolites (SCFAs, bile acids) | D | — Insufficient | not pooled; preclinical narrative only | — |
| Metabolic parameters (glycemia, lipids, weight) | D | — Insufficient | not pooled; preclinical narrative only | — |
| Safety and toxicity (interactions, target-organ) | D | — Insufficient | not pooled; narrative only, no formal safety data | — |
Context
MASLD affects a growing share of the global population and lacks universally approved pharmacotherapy. The gut microbiota modulates the gut–liver axis via SCFAs, bile acids, and LPS translocation, representing a plausible therapeutic target. TCM monomers are studied as modulators of this axis, but evidence is predominantly preclinical and fragmented.
What the study showed
The review synthesizes evidence from in vitro, in vivo (HFD rodent), and scarce human clinical studies on flavonoids (quercetin, naringin, hesperidin, anthocyanins, luteolin, kaempferol), triterpenoids (ginsenosides, GP2), and alkaloids. Preclinical studies report reductions in hepatic lipid accumulation, inflammation, and dysbiosis, but no consolidated absolute data or 95% CIs are systematically provided. Human studies are isolated and do not allow pooled effect estimation. No absolute data with 95% CI were extractable from this narrative review.
How it was done
Structured narrative review (not systematic, no meta-analysis). Search in PubMed, Web of Science, Scopus, and CNKI using combined MeSH and free terms. Included in vitro, in vivo, and clinical studies with identifiable monomers and mechanistic gut–liver axis data. Excluded complex prescriptions without identifiable monomers, reviews, and conference abstracts.
Effect magnitude
No consolidated effect size with 95% CI is reported; this is a narrative review without quantitative synthesis. Individual effects vary by compound, model, and outcome, preventing a single magnitude estimate.
Limitations
Narrative design without PROSPERO registration or formal risk-of-bias assessment (RoB 2 or ROBINS-I not applied). Extreme heterogeneity of models, doses, durations, and outcomes precludes quantitative synthesis. Most evidence is preclinical (rodent), with insufficient human causal evidence. Functional validation via fecal microbiota transplantation, germ-free models, or integrated multi-omics remains scarce. Oral bioavailability, dose–toxicity relationships, herb–drug interactions, and quality standardization issues remain unresolved.
In clinical practice
There is no basis to recommend TCM monomers as first- or second-line therapy for MASLD based on this review. Clinicians should maintain lifestyle intervention as the standard of care while awaiting randomized controlled trials with validated hepatic endpoints. Preclinical mechanistic studies justify literature surveillance, not prescription.
What is still missing
Randomized clinical trials with isolated monomers, validated histological hepatic endpoints, and long-term safety assessment are needed. Causal validation via fecal microbiota transplantation and germ-free models is essential to confirm the gut–liver axis role.