How a Japanese Herbal Medicine Protects the Gut from IBD

Summary: A Japanese herbal formula, Daikenchuto (DKT), which combines ginger, Japanese pepper, ginseng and maltose, reduced signs of colitis in a mouse model by restoring beneficial gut microbes and enhancing anti-inflammatory immune cells.

Source: RIKEN

Researchers Zhengzheng Shi and colleagues at the RIKEN Center for Integrative Medical Sciences (IMS) in Japan examined how a widely used herbal preparation affects colitis, a core form of inflammatory bowel disease (IBD).

Published in Frontiers in Immunology, their study reports that Daikenchuto (DKT) significantly reduced disease severity in mice with experimentally induced colitis. The protective effects were linked to DKT’s ability to rebalance the gut microbiome—particularly restoring Lactobacillus species—and to increase levels of innate immune cells in the colon that help limit inflammation.

Colitis is a chronic inflammation of the colon associated with disrupted gut microbial communities and an abnormal immune response. Its prevalence has risen globally over recent decades, making more effective therapies an urgent need. Conventional treatments can be partially effective but often fail to fully control the disease, prompting researchers to explore traditional herbal medicines used in East Asia for potential benefits.

Daikenchuto (DKT) is one of 148 Kampo herbal formulas developed in Japan. It contains defined amounts of Zanthoxylum fructus (Japanese pepper), processed ginger (Zingiberis siccatum rhizoma), ginseng root (Ginseng radix) and maltose powder. DKT is commonly prescribed in Japan for various gastrointestinal conditions, but molecular evidence supporting its therapeutic effects has been limited.

To clarify DKT’s mechanisms, the RIKEN team used a dextran sodium sulfate (DSS) model to induce colitis in mice. DSS damages the epithelial lining of the colon and triggers inflammation resembling aspects of human colitis. Mice treated with DKT maintained healthier body weight, displayed lower clinical scores for colitis and showed substantially less epithelial damage on pathological examination.

Following these observations, the researchers profiled the gut microbiome and assessed immune cell populations in the colon. Healthy gut microbiomes support digestion and immune regulation through diverse bacterial and fungal communities. In this study, DSS-induced colitis depleted members of the lactic acid bacteria family Lactobacillaceae and reduced levels of propionate, a short-chain fatty acid known for immunomodulatory properties.

This shows a woman's stomach
Colitis is a chronic inflammation of the colon, characterized by an imbalance in gut bacteria and an abnormal immune response. Image is in the public domain

Administration of DKT largely restored the depleted Lactobacillus populations and normalized propionate levels in the colon. These shifts in microbial composition and metabolite production correlate with improved epithelial integrity and reduced inflammation.

On the immune side, the investigators focused on innate lymphoid cells, specifically group 3 innate lymphoid cells (ILC3s). ILC3 numbers were reduced in untreated colitic mice but were preserved in mice receiving DKT. Importantly, genetically engineered mice lacking ILC3s experienced more severe disease and did not benefit from DKT treatment, indicating that ILC3s are essential mediators of the formula’s protective effect.

Further molecular analysis revealed that these ILC3s express the propionate receptor GPR43 (also known as FFAR2), suggesting a direct link between microbial metabolites and innate immune regulation. DKT also upregulated epithelial protective genes such as Fut2 (a fucosyltransferase) and Reg3g (an antimicrobial peptide), which likely contribute to maintaining mucosal barrier function.

“Daikenchuto is commonly prescribed to prevent and treat gastrointestinal diseases and to reduce intestinal obstruction following colorectal cancer surgery,” says Naoko Satoh-Takayama of RIKEN IMS. “Our findings show that DKT can also alleviate experimental colitis by restoring Lactobacillus populations in the gut and promoting activity of type 3 innate lymphoid cells, thereby reducing inflammatory responses.”

About this IBD research news

Author: Press Office
Source: RIKEN
Contact: Press Office – RIKEN
Image: The image is in the public domain

Original Research: Open access. “A Japanese Herbal Formula, Daikenchuto, Alleviates Experimental Colitis by Reshaping Microbial Profiles and Enhancing Group 3 Innate Lymphoid Cells” by Zhengzheng Shi et al., Frontiers in Immunology


Abstract

A Japanese Herbal Formula, Daikenchuto, Alleviates Experimental Colitis by Reshaping Microbial Profiles and Enhancing Group 3 Innate Lymphoid Cells

Daikenchuto (DKT) is a commonly used Japanese herbal formula for gastrointestinal disorders, composed of Zanthoxylum fructus (Japanese pepper), processed ginger, ginseng radix and maltose. Despite widespread clinical use, detailed molecular evidence for DKT’s therapeutic effects has been limited.

In the dextran sodium sulfate (DSS) model of colitis in mice, DKT markedly reduced disease severity. Treatment preserved beneficial members of the symbiotic microbiota, especially Lactobacillaceae, and increased levels of propionate, an immunomodulatory short-chain fatty acid, in the colon.

DKT also supported epithelial barrier integrity by upregulating Fut2 and the antimicrobial peptide gene Reg3g. Notably, DKT restored colonic group 3 innate lymphoid cells (ILC3s), predominantly RORγt-high ILC3s, which were reduced by DSS treatment. Mice deficient in ILC3s showed increased mortality in experimental colitis, indicating a protective role for these cells.

These findings demonstrate that DKT exerts anti-inflammatory activity in part through effects on ILC3s and by maintaining a favorable colonic microenvironment. The study provides mechanistic insight into how a traditional herbal formula can influence host–microbe–immune interactions and supports further investigation into herbal medicines as potential sources for therapeutic development.