This Ancient Chinese Herbal Formula Blocked Colon Tumors by Rewiring the Gut Microbiome

Colorectal cancer arising from long-term intestinal inflammation is one of the harder problems in gastroenterology, partly because it sits at the intersection of immune dysfunction, a disrupted gut microbiome, and runaway cell signaling. A new study published in Phytomedicine suggests that Lichang Decoction (LCD), a traditional Chinese medicine formula historically used for intestinal disorders, may address all three at once. The research is preliminary, conducted in mice, but the mechanisms it maps out are concrete enough to warrant attention.

Lichang Decoction Reduced Tumor Number and Size in CAC Mice

In a study published June 2026, Xie Y, Lin J, and colleagues at established the effect of LCD in an azoxymethane and dextran sulfate sodium (AOM+DSS) mouse model, the standard preclinical system for colitis-associated colorectal cancer (CAC). Mice treated with either low- or high-dose LCD showed significantly less weight loss, diarrhea, and rectal bleeding than untreated controls. More importantly, tumor number and size were markedly reduced, with high-dose LCD performing comparably to 5-fluorouracil, a frontline chemotherapy agent used as the positive control.

The team also measured a panel of inflammatory cytokines: serum and tissue levels of IL-1β, TNF-α, IL-6, and IFN-γ all dropped with LCD treatment. Infiltration by CD11b+ and MPO+ inflammatory cells, both markers of active immune assault on gut tissue, was similarly reduced. Goblet cell abundance, a proxy for a healthy mucus barrier, increased, and tight junction proteins recovered, indicating partial restoration of intestinal barrier integrity.

Chronic Gut Inflammation Raises Colorectal Cancer Risk Substantially

The clinical stakes of this work are real. Patients with inflammatory bowel disease (IBD) face significantly elevated colorectal cancer risk, with frequency rates of 2.1% among ulcerative colitis patients and 1.5% among Crohn's disease patients compared to the general population. That gap compounds over decades of living with chronic inflammation. Therapies that can interrupt the inflammation-to-tumor progression, rather than simply managing symptoms, represent a genuine unmet need. LCD's ability to simultaneously dampen inflammatory markers and reduce tumor burden in a mouse model at least raises the hypothesis that the formula might offer both functions.

The AOM+DSS Model and What the Molecular Data Revealed

The AOM/DSS mouse model is widely regarded as a reproducible and accurate recapitulation of human CAC, which gives the tumor burden data some translational credibility, even if the gap between mouse and human remains substantial. To understand how LCD was producing its effects, the team layered transcriptomic analysis, quantitative PCR, and Western blotting on top of the behavioral and histological readouts. The data pointed consistently to the Wnt/β-catenin signaling pathway, a well-established driver of colorectal cancer cell proliferation.

Specifically, LCD reduced expression of Wnt4, β-catenin, c-Myc, and cyclin D1, proteins that together push cells toward uncontrolled division when the pathway is overactive. Molecular docking analysis suggested that active constituents identified in LCD by ultra-performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS), including flavonoids, organic acids, and saponins, could physically interact with these pathway components. The link between Wnt/β-catenin signaling and gut microbiota in CAC has been described before: commensal bacteria modulate this pathway in intestinal immune cells, and its dysregulation is a recurring feature of colitis-driven tumor development.

Gut Bacteria Shift, and a Transplant Experiment Confirmed Causality

16S rRNA sequencing of stool samples showed that LCD reshaped the gut microbiome in treated mice. Abundance of Bacillota and Bacteroidota, two phyla associated with tumor-promoting microbial activity in this context, declined. Verrucomicrobiota, which includes bacteria linked to gut barrier health, increased. Correlation and functional prediction analyses tied these microbial shifts directly to changes in Wnt/β-catenin pathway activity and tumor progression markers.

The most telling experiment involved fecal microbiota transplantation (FMT). Stool from LCD-treated mice was transferred into pseudo-germ-free CAC mice, animals whose own microbiomes had been depleted with antibiotics. Those recipients showed reduced tumor progression, even without receiving LCD directly. The flip side is equally revealing: when LCD was administered directly to pseudo-germ-free mice without transplanting the altered microbiome, its tumor-suppressive effect largely disappeared. This suggests LCD's anticancer activity is substantially mediated by its impact on gut bacteria rather than by direct pharmacological action on tumor cells. A parallel in vitro experiment in HCT116 colorectal cancer cells similarly failed to show direct Wnt/β-catenin pathway suppression, reinforcing the microbiota-dependence interpretation.

Open Questions About Clinical Translation and Mechanism Scope

The microbiota-dependence finding is an important caveat for interpreting these results. LCD does not appear to act as a conventional small-molecule inhibitor that can be dosed into a patient and expected to hit tumor cells directly. Its effects, at least in this model, run through the microbial layer first. Whether those same microbial shifts occur reliably in humans, whose gut microbiomes are far more variable than those of inbred laboratory mice, remains entirely unknown.

The constituents identified by UPLC-MS/MS give researchers a starting point for bioavailability and pharmacokinetic studies, but traditional formulas like LCD are complex mixtures, and identifying which compound or compounds drive the microbial remodeling is a substantial research task on its own. Broader work on TCM formulations in cancer immunotherapy highlights exactly this challenge: poor solubility and low bioavailability of active compounds are recurring barriers to clinical translation. Future studies will need to establish whether LCD or its purified components can reproduce these gut microbiome effects in higher organisms, and whether those effects translate to reduced tumor incidence in humans with IBD. For now, the data offer a mechanistically coherent preclinical rationale, which in this field is a meaningful first step.

Evidence rating

INVESTIGATIONAL — 69/100

Caveats:

• All findings are from a mouse model only; no human data exist for this intervention.
• LCD showed no tumor-suppressive effect in germ-free mice given LCD directly, meaning the effect depends entirely on gut microbiota that may differ substantially between mice and humans.
• LCD had no effect on the Wnt/β-catenin pathway in human colorectal cancer cells (HCT116) tested in isolation, raising questions about direct applicability to human tumor biology.
• Funding source was not disclosed by the authors.
• This is a single study with no independent replication.

This is a preclinical mouse study using the AOM+DSS colitis-associated colorectal cancer model; no human subjects were enrolled. The study demonstrates association and partial causal mechanism via FMT experiments, but findings have not been replicated in an independent laboratory or translated to human populations. The observation that Lichang Decoction failed to suppress tumors in germ-free mice and had no effect on Wnt/β-catenin signaling in human cancer cells in vitro introduces important limitations on the generalizability of conclusions.

References

1. Yimin Xie, Jinghong Lin, Zishan Huang, et al. (2026). Lichang decoction suppresses AOM+DSS-induced colitis-associated cancer via regulating intestinal flora and suppressing the Wnt/β-catenin signaling pathway. Phytomedicine. https://doi.org/10.1016/j.phymed.2026.158385
2. Naim Abu-Freha, Bracha Cohen, Michal Gordon, et al. (2023). Colorectal cancer among inflammatory bowel disease patients: risk factors and prevalence compared to the general population. Frontiers in Medicine. https://doi.org/10.3389/fmed.2023.1225616
3. AOM/DSS Model of Colitis-Associated Cancer. NIH. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3539827/
4. Daniel Swafford, Arulkumaran Shanmugam, Punithavathi Ranganathan, et al. (2020). The Wnt–β-Catenin–IL-10 Signaling Axis in Intestinal APCs Protects Mice from Colitis-Associated Colon Cancer in Response to Gut Microbiota. The Journal of Immunology. https://doi.org/10.4049/jimmunol.1901376
5. Yanyun Li, Changying Li, Junzi Fan, Yutong Liu, Yincong Xu, Guowei Pang (2025). The Application of Traditional Chinese Medicine-Derived Formulations in Cancer Immunotherapy: A Review. Cancer Management and Research. https://doi.org/10.2147/cmar.s503071