How a Licorice Compound Starves Colon Cancer by Changing Gut Bacteria

If you have been digging into why gut health keeps coming up in cancer research, a new study gives one of the clearest mechanistic pictures yet. Researchers in China found that licorice flavonoids (LF), a group of plant compounds extracted from licorice root (Glycyrrhiza uralensis), slowed colorectal tumor growth in mice by changing which bacteria live in the gut. The payoff of that change was a chain reaction: more cancer-suppressing gut bacteria, more of the fatty-acid byproducts those bacteria make, and less activity from a tumor-promoting enzyme called IDO1 (indoleamine 2,3-dioxygenase 1). The study, published in Pharmacological Research, is early-stage and entirely in mice, but it maps a specific gut-to-tumor pathway in unusually fine detail.

Key takeaways

• Licorice flavonoids (LF) significantly slowed colorectal tumor growth in two separate mouse models; the higher dose performed comparably to regorafenib, a drug already approved for colorectal cancer.
• The effect traces back to gut bacteria: LF enriched three fatty-acid-producing genera, and transplanting stool from LF-treated mice into untreated mice reduced their tumors too.
• Those bacterial byproducts, called SCFAs, and LF itself both shut down the cancer-supporting enzyme IDO1; mice genetically missing IDO1 lost most of LF's protective effect.
• This is mouse-only, mechanistic research. Human dosing, pharmacokinetics, and clinical relevance have not been established.

Licorice Flavonoids Cut Colon Tumors by Reshaping Gut Bacteria

Licorice flavonoids significantly reduced tumor counts in two separate mouse models of colorectal cancer: one triggered by a carcinogen plus induced inflammation (the AOM/DSS model), the other driven by a cancer-prone gene mutation (the Apc min/+ model). The higher LF dose (416 mg/kg) performed comparably to regorafenib, a drug already approved for colorectal cancer that was used here as the positive control. Beyond shrinking tumors, LF restored the integrity of the intestinal lining, measured by the recovery of barrier proteins like E-cadherin and ZO-1 that keep the gut wall sealed. The researchers then traced the effect to the gut microbiome itself: 16S rRNA gene sequencing showed LF enriched three bacterial genera, Parabacteroides, Paramuribaculum, and Parasutterella, all previously linked to gut barrier support and the production of short-chain fatty acids (SCFAs, fatty acids bacteria make by fermenting fiber). One of those SCFAs, butyrate, has separately been shown to suppress IDO1 expression in human intestinal cells, lending outside support to the mechanism this study traces in mice.

Why Colorectal Cancer Patients and Their Families Should Care

Colorectal cancer is one of the most common and deadliest cancers worldwide, and gut microbial imbalance is increasingly treated as a contributor to its development, not just a bystander. People managing inflammatory bowel disease have particular reason to pay attention: the AOM/DSS model used here is designed to mimic inflammation-driven, colitis-associated cancer, the route by which chronic gut inflammation can progress toward malignancy. The study's core contribution is showing that a plant-derived compound can interrupt that route partly by reshaping the gut's bacterial community, and partly by directly dialing down IDO1 inside tumor cells. IDO1 works by converting the amino acid tryptophan into kynurenine, a byproduct that helps tumors evade the immune system, which is why suppressing it is a strategy of growing interest in cancer research well beyond this one study.

Inside the Two Mouse Models and the Methods Used

To test LF's effects, the team gave 8-week-old male mice a single dose of the carcinogen AOM followed by three rounds of the gut irritant DSS, then tracked them for 80 days. A second, genetically driven model, Apc min/+ mice that spontaneously develop intestinal tumors, was tracked for 90 days. Mice received either a placebo, regorafenib, or one of two LF doses (208 or 416 mg/kg). To confirm the microbiome's role rather than just notice a correlation, the researchers ran a fecal microbiota transplant: mice that received stool from LF-treated donor mice developed fewer tumors and longer colons than mice given stool from untreated donors, even though the recipients themselves never received LF directly. A separate group of mice had their gut bacteria wiped out with antibiotics ("pseudosterile" mice) to isolate which of LF's benefits require a microbiome and which do not; LF still shrank tumors in these mice, just through a different, direct route into the cancer cells. Finally, the team used CRISPR gene editing to build IDO1 knockout mice entirely lacking the gene, to test whether IDO1 was essential to LF's benefit at all.

What This Could Mean for Someone Managing Their Own Gut Health

This is mechanistic, early-stage animal research, not a reason to start taking a licorice supplement for cancer prevention. Nothing here establishes a dose, formulation, or timeline that would apply to a human body, and the LF used in this study is a purified, concentrated flavonoid extract from licorice root, not the licorice candy or tea sold on store shelves. What is worth watching is the broader idea the study supports: that specific gut bacteria and the SCFAs they produce may be able to shut down a cancer-promoting pathway like IDO1 directly, through diet, fiber, or future targeted interventions, rather than only through a drug that blocks the enzyme from outside the cell. If you are already managing a gut-related condition or a family history of colorectal cancer, this is a reasonable study to mention to your doctor as background context, not as a basis for a supplement decision.

The Study's Key Limitations and Open Questions

The clearest limitation is the one the researchers themselves name: this is mouse-model and cell-culture work, and mouse gut microbiota, metabolism, and immune responses differ from human ones in ways that matter for translation. The authors explicitly note that LF's pharmacokinetics and oral bioavailability in humans have not been characterized, a prerequisite for any future human trial. They also describe the link between LF's suppression of WNT and TGF-beta signaling (two cell-signaling pathways involved in tumor growth) and IDO1 suppression as correlative rather than fully proven causal, and the exact molecular receptor or epigenetic mechanism by which SCFAs switch off IDO1 inside tumor cells was not identified in this study. No patient-derived tissue or clinical samples were tested; the cell-line experiments used established human colon cancer cell lines, not fresh patient material.

What Comes Next for This Gut-Bacteria-to-Enzyme Pathway

The research team points to several next steps: testing LF in humanized-microbiota mouse models or patient-derived tumor organoids, which would better approximate the human gut and tumor environment; directly measuring IDO1 enzymatic activity rather than inferring it from downstream metabolites; and running functional immune assays to see whether the same IDO1 suppression that slows tumor growth in mice also restores anti-tumor immune activity in that setting. Any path toward human relevance would also require establishing safe, effective doses and confirming the compound reaches the colon in active form, standard early hurdles for any natural-product candidate moving toward clinical testing.

Common Questions

Does this mean licorice prevents colon cancer in people? Not yet. The anti-tumor effects shown here came from a purified flavonoid extract tested in mice, not everyday licorice candy or tea, and no human trials have tested it for cancer prevention.

What are SCFAs and why do they matter here? Short-chain fatty acids (SCFAs) are byproducts certain gut bacteria make when they ferment fiber. In this study, SCFAs like butyrate and valeric acid directly suppressed IDO1 and slowed the growth of colon cancer cells.

What is IDO1 and why does it matter for cancer? IDO1 is an enzyme that breaks down the amino acid tryptophan into kynurenine, a byproduct that can help tumors evade the immune system. Blocking IDO1 is an active area of cancer research well beyond this study.

Is the licorice extract in this study the same as the licorice in candy? No. The study used a concentrated extract of licorice flavonoids from the root of Glycyrrhiza uralensis, a different exposure than the small amounts of licorice flavoring used in most candy or tea.

References

1. Yamei Li, Junya Wen, Dehao Huang, et al. (2026). IDO1 integrates gut microbiota-derived SCFAs signals and host WNT/TGF-β pathways to mediate the anti-colorectal cancer effects of licorice flavonoids. Pharmacological Research. https://doi.org/10.1016/j.phrs.2026.108474
2. Camille Martin-Gallausiaux, Pierre Larraufie, Anne Jarry, et al. (2018). Butyrate Produced by Commensal Bacteria Down-Regulates Indolamine 2,3-Dioxygenase 1 (IDO-1) Expression via a Dual Mechanism in Human Intestinal Epithelial Cells. Frontiers in Immunology. https://doi.org/10.3389/fimmu.2018.02838
3. Gholamreza Roshandel, Fatemeh Ghasemi-Kebria, Reza Malekzadeh (2024). Colorectal Cancer: Epidemiology, Risk Factors, and Prevention. Cancers. https://doi.org/10.3390/cancers16081530
4. Dongni Shi, Xianqiu Wu, Yunting Jian, et al. (2022). USP14 promotes tryptophan metabolism and immune suppression by stabilizing IDO1 in colorectal cancer. Nature Communications. https://doi.org/10.1038/s41467-022-33285-x