How a Japanese Herbal Medicine Protects the Gut Against Inflammatory Bowel Disease

Summary: DKT, a Japanese herbal remedy containing ginger, pepper, ginseng, and maltose, reduced symptoms of colitis in mice, a new study reports.

Source: RIKEN

Zhengzheng Shi and colleagues at the RIKEN Center for Integrative Medical Sciences (IMS) in Japan report the effects of a common herbal remedy on colitis, one of two conditions that comprise inflammatory bowel disease (IBD).

Published in Frontiers in Immunology, the study shows that DKT—a standard formula containing ginger, pepper, ginseng, and maltose—reduced the severity of colitis in lab mice by preventing the characteristic imbalance in gut microbes and by increasing levels of immune cells in the colon that fight inflammation.

Colitis is a chronic inflammation of the colon, characterized by an imbalance in gut bacteria and an abnormal immune response. Prevalence has doubled over the last 20 years, and it’s currently a global health concern, particularly in Europe and North America. Although treatments are numerous, they are only partially effective.

This has led some researchers to take a closer look at traditional herbal medicines that originated in China, and are now commonly used in Japan and other Asian countries.

Daikenchuto (DKT) is a formula containing specific amounts of ginger, pepper, ginseng, and maltose, and is one of 148 herbal medicines called Kampo, which have been developed in Japan and are often prescribed by doctors to treat a variety of illnesses.

Previous research has hinted that DKT might be useful for treating colitis, but evidence, particularly at the molecular level, has been lacking. Thus, Shi and the team of researchers at RIKEN IMS led by Naoko Satoh-Takayama conducted a detailed examination of its effects on a mouse model of colitis.

Colitis was induced in mice using dextran sodium sulfate, which is toxic to the cells that line the colon. When these mice were given DKT, their body weights remained normal, and they had lower clinical scores for colitis. Additional analysis revealed much less damage to the cells lining the colon.

Having thus shown that DKT does indeed help protect against colitis, the researchers proceeded to analyze the gut microbiome of the mice and expression levels of anti-inflammatory immune cells.

Gut microbiomes contain numerous bacteria and fungi that aid in digestion and help the immune system.

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

Colitis is associated with an imbalance in these gut microbiota, and analysis showed that a family of lactic acid bacteria were depleted in the colitic mice of this study. Also depleted was one of their metabolites, a short-chain fatty acid called propionate.

Treating the model mice with DKT restored much of these missing bacteria—particularly those from the genus Lactobacillus—and levels of propionate were normal.

Colitis is also associated with an abnormal immune response that causes the characteristic intestinal inflammation.

When the team looked at innate intestinal immune cells, they found that levels of a type called ILC3 were lower in the untreated colitic mice than in the DKT-treated colonic mice, and that mice engineered to lack ILC3 suffered more and could not benefit from DKT treatment.

This means that ILC3s are critical for protecting against colitis and that DKT works by interacting with them. Lastly, qPCR analysis indicated that these important immune cells had receptors for propionate, called GPR43, on their surface.

“Daikenchuto is commonly prescribed to prevent and treat gastrointestinal diseases, as well as for reducing intestinal obstruction after colorectal cancer surgery,” says Satoh-Takayama.

“Here we have shown that it can also alleviate intestinal diseases like colitis by rebalancing Lactobacillus levels in the gut microbiome. This likely helps reduce inflammatory immune responses by promoting the activity of type 3 innate lymphoid cells.”

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


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

Daikenchuto (DKT) is one of the most widely used Japanese herbal formulae for various gastrointestinal disorders. It consists of Zanthoxylum Fructus (Japanese pepper), Zingiberis Siccatum Rhizoma (processed ginger), Ginseng radix, and maltose powder. However, the use of DKT in clinical settings is still controversial due to the limited molecular evidence and largely unknown therapeutic effects.

Here, we investigated the anti-inflammatory actions of DKT in the dextran sodium sulfate (DSS)-induced colitis model in mice.

We observed that DKT remarkably attenuated the severity of experimental colitis while maintaining the members of the symbiotic microbiota such as family Lactobacillaceae and increasing levels of propionate, an immunomodulatory microbial metabolite, in the colon.

DKT also protected colonic epithelial integrity by upregulating the fucosyltransferase gene Fut2 and the antimicrobial peptide gene Reg3g. More remarkably, DKT restored the reduced colonic group 3 innate lymphoid cells (ILC3s), mainly RORγthigh-ILC3s, in DSS-induced colitis. We further demonstrated that ILC3-deficient mice showed increased mortality during experimental colitis, suggesting that ILC3s play a protective function on colonic inflammation.

These findings demonstrate that DKT possesses anti-inflammatory activity, partly via ILC3 function, to maintain the colonic microenvironment.

Our study also provides insights into the molecular basis of herbal medicine effects, promotes more profound mechanistic studies towards herbal formulae and contributes to future drug development.

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