Mechanisms of the gut-lung axis in regulating lung metastasis of colorectal cancer and advances in traditional Chinese medicine intervention

Table 2 Representative traditional Chinese medicine formulas/compounds targeting the gut-axis in colorectal cancer lung or liver metastasis

Intervention	Type	Model	Effect on lung metastasis	Gut-lung axis mechanism	Ref.
Si-Jun-Zi decoction	Formula	Orthotopic CRC mouse	↓ 47% nodules	↑ SCFA producers, ↓ F. nucleatum, ↑ gut barrier (ZO-1)	[98]
Hedyotis diffusa-Scutellaria barbata	Herb pair	Xenograft (tail vein)	↓ 62% metastatic area	↓ MMP-2/9, ↓ TAMs in lung, ↓ TGF-β/Smad	[100]
Baicalin	Flavonoid	Azoxymethane/DSS + CRC	↓ Liver metastasis (lung not reported)	Restored gut microbiota, reversed EMT	[106]
Berberine	Alkaloid	HFD-induced CRC mouse	↓ Liver metastasis	Modulated lysophosphatidylcholine, ↓ DNMTs	[110]
Astragalus polysaccharides	Polysaccharide	CT26 lung metastasis model	↓ 52% nodules	↑ Gut barrier, ↑ M1 macrophages	[113]
Astragalus-derived exosome-like nanoparticles	Nanoparticle	Subcutaneous CT26	↓ Tumor growth (metastasis not quantified)	Ferroptosis, M2→M1 polarization, gut microbiota shift	[114]

CRC: Colorectal cancer; SCFA: Short-chain fatty acid; F. nucleatum: Fusobacterium nucleatum; ZO-1: Zonula occludens-1; MMP-2/9: Matrix metalloproteinase-2/9; TAMs: Tumor-associated macrophages; TGF-β: Transforming growth factor beta; DSS: Dextran sulfate sodium; EMT: Epithelial-mesenchymal transition; HFD: High-fat diet; DNMTs: DNA methyltransferases.