AS-IV inhibits chronic colitis by regulating gut microbiota composition, butyric acid metabolism, and Th17/Treg cell differentiation balance, whose protective effects are dependent on the regulatory mechanism of Th17/Treg cell differentiation balance mediated by gut microbiota-derived butyrate metabolism.
Key Findings
Results
Astragaloside IV (AS-IV) effectively alleviated DSS-induced chronic colitis in mice as measured by multiple physical and histological parameters.
Chronic colitis was induced by free access to 2.5% dextran sulfate sodium (DSS) solution over three 7-day cycles with concurrent AS-IV administration.
AS-IV treatment resulted in increased body weight and colon length compared to DSS controls.
AS-IV decreased disease activity index (DAI), colon weight, colon weight/colon length ratio, and colon weight index.
AS-IV enhanced gene and protein expression of tight junction molecules Claudin-1, Occludin, and ZO-1.
Results
AS-IV regulated the differentiation balance of Th17/Treg cells in chronic colitis mice.
AS-IV not only effectively regulated the differentiation balance of Th17/Treg cells in DSS-induced chronic colitis mice.
Th17/Treg cell balance was assessed in the context of gut microbiota and butyric acid metabolism modulation.
The regulatory effect on Th17/Treg balance was lost following gut microbiota depletion, indicating microbiota dependence.
Results
AS-IV significantly improved gut microbiota composition and butyric acid metabolism in chronic colitis mice.
AS-IV significantly improved the composition of gut microbiota in chronic colitis mice.
AS-IV improved butyric acid metabolism in chronic colitis mice.
Th17/Treg cells and butyric acid were significantly correlated with α/β diversity as well as the genera Enterorhabdus, Mucispirillum, and Helicobacter.
Results
AS-IV lost its therapeutic efficacy against colitis and its regulatory effects on Th17/Treg cell balance and butyric acid metabolism following gut microbiota depletion.
Gut microbiota depletion abolished AS-IV's protective effects against DSS-induced colitis.
Following gut microbiota depletion, AS-IV's regulatory effects on Th17/Treg cell balance were eliminated.
Butyric acid metabolism regulation by AS-IV was also abolished after gut microbiota depletion, demonstrating that these effects are microbiota-dependent.
Results
Fecal microbiota transplantation (FMT) from AS-IV-treated mice restored protective effects against colitis and regulation of Th17/Treg cell balance and butyric acid metabolism.
FMT from AS-IV-treated mice was performed in microbiota-depleted colitis mice.
FMT restored the protective effects against colitis that were lost after microbiota depletion.
FMT restored the regulation of Th17/Treg cell balance and butyric acid metabolism, confirming that the gut microbiota mediates AS-IV's therapeutic effects.
Results
Specific gut microbial genera including Enterorhabdus, Mucispirillum, and Helicobacter were significantly correlated with Th17/Treg cells and butyric acid levels.
Th17/Treg cells and butyric acid were significantly correlated with α/β diversity.
The genera Enterorhabdus, Mucispirillum, and Helicobacter were specifically identified as significantly correlated with both Th17/Treg cell balance and butyric acid metabolism.
These correlations suggest these genera may play key roles in mediating the gut microbiota–butyrate–immune axis modulated by AS-IV.
Zhong Y, Liu J, Huang J, Yu J, Liu Y, Zhuo W, et al.. (2026). Astragaloside IV alleviates ulcerative colitis via gut microbiota - butyrate metabolism axis to reshape Th17/Treg balance.. International immunopharmacology. https://doi.org/10.1016/j.intimp.2025.116135