For the roughly 3 million Americans living with inflammatory bowel disease, the current treatment options tell a frustrating story. Anti-TNF biologics such as infliximab and adalimumab, the backbone of modern IBD therapy, fail to produce a meaningful response in an estimated 30 to 40 percent of patients. Many who do respond eventually lose that benefit. The pipeline for new drugs has been slow, partly because the tools used to find them, animal models and immortalized cell lines, are imperfect stand-ins for the human gut.
A study published in May 2026 in Stem Cell Reports offers a different approach. Researchers built miniature replicas of the human intestinal lining from stem cells and used them to screen drug candidates against a central driver of IBD tissue damage. Out of that screen, one compound stood out: glycyrrhizin, a molecule derived from black licorice root. The finding does not mean licorice treats IBD. But it does suggest that lab-grown human gut tissue can surface drug leads that older methods might miss.
Growing a gut in a dish
The miniature structures at the center of this work are called intestinal organoids. Grown from human induced pluripotent stem cells, they self-organize into three-dimensional clusters that mirror the architecture of the real intestinal lining, complete with the specialized cell types that absorb nutrients, secrete mucus, and form a barrier against bacteria.
Earlier work, published in Nature Communications, established methods for generating these organoids without the mesenchyme, the connective tissue layer that normally wraps around the gut lining. Stripping that layer away lets researchers isolate the epithelium and standardize cultures under defined, reproducible conditions. That standardization is what makes it practical to test hundreds or thousands of compounds in parallel, turning organoids from a research curiosity into a screening platform.
Compared with immortalized cell lines, which have been the workhorses of laboratory drug screening for decades, organoids offer a more realistic readout. Immortalized lines are genetically altered to grow indefinitely, a convenience that comes at the cost of biological fidelity. Organoids, whether derived from patient biopsies or stem cells, retain the cell-type diversity and functional behavior that matter when modeling a complex disease like IBD.
How the screen worked
The researchers exposed their organoids to tumor necrosis factor, or TNF, a protein that triggers the kind of epithelial cell death observed in IBD patients. TNF is not a speculative target. It is the same molecule that existing biologic drugs aim to neutralize, and separate mechanistic research has confirmed that TNF-induced death in intestinal organoids is a cell-autonomous phenotype tied to the regulatory factor A20. In plain terms, the damage happens within the epithelial cells themselves, without requiring immune cells to be present. That distinction validates the organoid setup: you can study this specific injury mechanism in isolation.
After dosing the organoids with TNF, the team screened a library of compounds to identify those that could block the resulting cell death. Glycyrrhizin, a triterpenoid saponin that gives licorice root its characteristic sweetness, emerged as a top protector. It conferred measurable, reproducible protection against TNF-induced damage in the organoid system.
Why glycyrrhizin is interesting but not ready for patients
Glycyrrhizin has a long history in traditional medicine and a substantial preclinical record. Reviews have mapped its anti-inflammatory mechanisms across several models of intestinal disorders, documenting its ability to dampen inflammatory signaling, reduce oxidative stress, and help preserve barrier function. The new organoid data add to that picture by showing a protective effect in human-derived tissue, a step closer to clinical relevance than rodent studies or non-intestinal cell lines.
But there is a significant catch. Glycyrrhizin has mineralocorticoid-like effects. It can cause the body to retain sodium and lose potassium, leading to hypertension and hypokalemia, a potentially dangerous drop in potassium levels. These are not rare side effects at pharmacologically active doses. Any serious effort to move glycyrrhizin toward IBD patients would need to address those risks, likely through chemical modification of the molecule or tightly controlled dosing. No clinical trial has tested glycyrrhizin specifically for Crohn’s disease or ulcerative colitis.
To be clear: eating black licorice will not treat IBD. The concentrations used in a laboratory screen bear no relationship to what a person would absorb from candy or herbal tea, and the safety concerns make unsupervised use genuinely risky.
What the organoid platform still cannot do
As faithful as these organoids are, they remain simplified versions of a living gut. They capture epithelial biology with impressive accuracy but do not fully replicate the immune cell infiltration, microbial colonization, or vascular changes that define IBD in a patient. Researchers have engineered more complex enteroid-derived tissue models that display innate immune responses and IBD-relevant gene activation patterns, but even those systems are simplified compared with the full disease environment. A compound that shields organoid epithelium from TNF might behave differently once immune cells, bacteria, and blood flow enter the picture.
Genetic diversity poses another challenge. Recent work has shown that type I and III interferons can synergize with TNF to amplify intestinal epithelial damage, and that organoids carrying a specific IBD risk allele display distinct vulnerability patterns. Whether glycyrrhizin’s protective effect holds across organoids derived from patients with different genetic backgrounds has not been reported. IBD is not one disease but a spectrum of conditions with varied genetic and environmental triggers, and a compound that works in one genetic context may fall short in another.
Scalability questions also remain open. The published protocols describe defined, reproducible conditions, but the literature does not include detailed assessments of throughput capacity for high-volume commercial screening. Moving from a research-grade assay to an industrial drug discovery pipeline requires automation, quality controls, and cost structures that have not been publicly documented for this specific organoid system. Batch-to-batch variability, long-term genetic stability of the stem cell lines, and cost per assay will all influence whether pharmaceutical companies adopt the platform at scale.
The platform may matter more than the compound
Perhaps the most durable takeaway from this research is not glycyrrhizin itself but the validation of organoid-based phenotypic screening as a discovery tool. Even if glycyrrhizin ultimately proves too toxic or insufficiently effective in living patients, the same methodology could surface other molecules with better safety profiles. The platform enables systematic testing of large compound libraries directly on human gut tissue analogs, filtering out ineffective or broadly toxic candidates before they ever reach a clinical trial.
That matters because the current drug discovery pipeline for IBD is long, expensive, and littered with late-stage failures. Organoid screens will not replace the need for rigorous clinical evaluation. Translating any laboratory finding into an approved therapy still requires years of optimization, preclinical testing, and multi-phase trials. But by providing a more human-relevant filter at the earliest stages, organoid platforms could reduce the number of dead ends and focus resources on compounds with a genuine shot at helping patients.
For now, the evidence supports cautious optimism. Human intestinal organoids are beginning to deliver actionable leads for IBD drug discovery. Glycyrrhizin is an illustrative first example of what this technology can uncover, not a proven treatment. The real promise lies in what comes next: larger screens, more diverse genetic backgrounds, and eventually, compounds that survive the long journey from a dish to a prescription.
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*This article was researched with the help of AI, with human editors creating the final content.
