Citrus scent compounds could influence gut inflammation, review says

Scientists are examining how plant-based compounds found in citrus fruits and herbs may interact with inflammatory pathways and the intestinal lining, while also asking how well laboratory findings match real-world dietary intake.

Study: Gut anti-inflammatory potential of dietary-relevant terpenoids: a critical overview. Image Credit: Roman3dArt / Shutterstock

A recent review in Food & Function looked at published experimental and clinical evidence on the gut anti-inflammatory potential of dietary-relevant terpenoids.

The authors drew on cellular studies, animal models, and clinical trials to examine low-molecular-weight monoterpenes and sesquiterpenes, mapping how these compounds may influence intestinal inflammation and epithelial barrier dysfunction.

Overall, the review found that some aromatic compounds from fruits, vegetables, culinary herbs, and volatile plant oils can reduce inflammatory signaling and strengthen gut barrier function in experimental settings, but similar benefits have not been shown in humans.

The researchers said that translational challenges, incomplete knowledge of how the human gut microbiota processes these compounds, and a lack of clinical data currently limit their therapeutic use, and they pointed to the need for more study.

Background

Chronic gastrointestinal inflammation remains a major global health problem, with inflammatory bowel disease affecting millions of people worldwide.

This broad category includes several disorders of the gastrointestinal tract, such as inflammatory bowel disease, which encompasses Crohn's disease and ulcerative colitis. Irritable bowel syndrome is a separate disorder of gut-brain interaction that may involve low-grade immune activation. These conditions differ in both mechanism and treatment.

Standard care includes anti-inflammatory drugs and immunosuppressants, which can help control intestinal inflammation but may cause side effects with long-term use, as well as biologic therapies aimed at inducing or maintaining remission. Responses to treatment also vary from person to person.

As microbiome and molecular research has advanced, scientists have increasingly explored dietary secondary plant metabolites as possible nutritional supports, although evidence that they improve drug effectiveness or reduce treatment side effects is still lacking.

Among these compounds are volatile terpenoids such as limonene, myrcene, citral, and geraniol, which are found in fruits, vegetables, herbs, and volatile plant oils. They occur in foods and drinks including citrus fruits, herbal infusions, and culinary spices, but their effects on mucosal injury in humans remain unclear.

About the review

The review set out to close these knowledge gaps by examining preclinical and clinical studies identified through a targeted search of English-language papers in PubMed up to May 2026.

It focused on four chemical classes of dietary terpenoids: hydrocarbon and oxygenated monoterpenes, and hydrocarbon and oxygenated sesquiterpenes. Compounds discussed included limonene, myrcene, perillyl alcohol, linalool, geraniol, citral, alpha-bisabolene, valencene, alpha-bisabolol, and nootkatone. The authors also considered nanoencapsulation as a separate delivery strategy.

They additionally reviewed evidence on phase I cytochrome P450 enzymes and phase II conjugation enzymes, such as UDP-glucuronosyltransferases, to assess how metabolism might affect bioavailability.

Finally, the analysis covered cellular pathways including nuclear factor kappa B, mitogen-activated protein kinases, peroxisome proliferator-activated receptor gamma, and tight junction proteins linked to epithelial barrier integrity, as measured by transepithelial electrical resistance.

Main targets affected by dietary terpenoids. Upon binding of an inflammatory stimulus, cells can activate the NF-κB pathway, leading to the nuclear translocation of p65 and inducing the expression of inflammatory markers. In addition, cells can activate p38, ERK and JNK pathways, culminating in the activation of AP-1, which also triggers the expression of inflammatory markers. PPAR-γ counters the inflammatory response by inhibiting AP-1 and p65 nuclear translocation or by migrating itself to the nucleus and inducing the expression of anti-inflammatory markers. Circled arrows indicate that terpenoids can induce activation, while squared arrows indicate an inhibitory effect.

Review findings

The review brought together evidence showing that several commonly consumed terpenoids can produce anti-inflammatory effects in cell studies and rodent colitis models.

In laboratory cell experiments, compounds such as alpha-bisabolol and citral showed anti-inflammatory activity, lowering certain pro-inflammatory cytokines, including interleukin-1 beta, interleukin-6, and tumor necrosis factor-alpha, and in some models reducing inducible nitric oxide synthase and cyclooxygenase-2.

In studies using intestinal epithelial cells, (S)-(-)-limonene and citral improved barrier function by altering different tight junction proteins. Limonene increased zonula occludens-1 and occludin protein levels in unchallenged cells, and raised occludin and claudin-1 gene expression under inflammatory conditions, while citral increased zonula occludens-1 and claudin-3 expression. Both compounds also increased transepithelial electrical resistance and reduced paracellular permeability.

Preclinical work in rodent models of dextran sodium sulfate-induced colitis showed that oral myrcene, perillyl alcohol, and geraniol improved measures of disease severity, including colon shortening or tissue damage, and reduced inflammatory activity. Perillyl alcohol also lowered splenomegaly, and several treatments reduced myeloperoxidase activity, a marker of neutrophil infiltration and mucosal injury, compared with untreated controls. The authors noted that many laboratory and animal studies used doses higher than typical dietary exposure, so the amount that can be reached through ordinary foods is uncertain.

Human evidence remains very limited. The review identified only two small trials of geraniol-based interventions in irritable bowel syndrome: one uncontrolled study with 19 patients and one double-blind, placebo-controlled trial with 56 patients. In the controlled trial, 52% of treated participants achieved at least a 50-point reduction in irritable bowel syndrome symptom severity score with a geraniol-rich palmarosa oil formulation containing ginger root, and the responder rate was significantly different from placebo.

Participants also reported less abdominal bloating and fewer days with pain than controls. However, because the formulation included other ingredients, the effects cannot be attributed to geraniol alone. The controlled trial found no significant differences between groups in circulating pro-inflammatory cytokines, and neither study measured geraniol metabolites, leaving their role unclear. Symptom improvement in irritable bowel syndrome does not prove reduced intestinal inflammation in humans.

Conclusions

The review concluded that dietary terpenoids may help support epithelial barrier integrity and reduce gut mucosal inflammation in laboratory and animal models, but it does not show that normal dietary intake produces the same results.

The authors also discussed emerging nanoencapsulation approaches using lipid nanocarriers or chitosan polymers as possible ways to address poor water solubility and losses from volatility and degradation during food processing. Still, clinical benefits from these delivery systems have not yet been demonstrated.

They said future work will need large clinical trials, detailed metabolomic profiling of gut microbiota biotransformation, realistic dietary dosing, pharmacokinetic measurements, and long-term safety monitoring before dietary terpenoids can be translated into evidence-based strategies for gastrointestinal health.

Source:

Journal reference:

• Zadra, M., Alves-Silva, J. M., Melillo, E., Beekwilder, J., & dos Santos, C. N. (2026). Gut anti-inflammatory potential of dietary-relevant terpenoids: a critical overview. Food & Function.