Gluten-Free Diet and Other Celiac Disease Therapies: Current Understanding and Emerging Strategies.

A lifelong gluten-free diet (GFD) is the only treatment for celiac disease and other gluten-related disorders. Nevertheless, strict adherence to the GFD is often challenging due to concerns about social isolation, risk of gluten contaminations, high cost, poor quality and the taste of gluten-free products. Moreover, although the GFD is effective in achieving mucosal healing, it may lead to dietary imbalances due to nutrient deficiencies over a long period of time. To overcome these issues, several gluten-free wheat flours have been developed to create products that closely resemble their gluten-containing counterparts. Furthermore, given the critical importance of adhering to the GFD, it becomes essential to promote adherence and monitor possible voluntary or involuntary transgressions. Various methods, including clinical assessment, questionnaires, serology for celiac disease, duodenal biopsies and the detection of Gluten Immunogenic Peptides (GIPs) are employed for this purpose, but none are considered entirely satisfactory. Since adherence to the GFD poses challenges, alternative therapies should be implemented in the coming years to improve treatment efficacy and the quality of life of patients with celiac disease. The aim of this narrative review is to explore current knowledge of the GFD and investigate its future perspectives, focusing on technology advancements, follow-up strategies and insights into a rapidly changing future.

Nutritional Biomarkers for the Prediction of Response to Anti-TNF-α Therapy in Crohn's Disease: New Tools for New Approaches.

Crohn's disease (CD) is a chronic disorder of the digestive tract characterized by an uncontrolled immune-mediated inflammatory response in genetically predisposed individuals exposed to environmental risk factors. Although diet has been identified as one of the major environmental risk factors, the role of nutrients in the clinical management of CD patients has not yet been fully investigated. In this prospective observational study, fifty-four patients diagnosed with active Crohn's disease and undergoing anti-TNF-α biological therapy were enrolled and subjected to nutrient intake analysis through a daily food diary. Their nutrient intake and blood values were analyzed before and after 6 months of biological therapy. After 6 months of anti-TNF-α, four patients dropped out of the study, leaving 29 patients in clinical remission and 21 still with active disease that remained the same. The aim of this study was to identify nutrients whose intake or blood values may be associated with patients' responses to biological therapy. In the diet, patients remaining with active CD showed very similar nutrient dietary intake compared to patients achieving remission except for a trend for lower starting zinc intake, below the reference value. In the blood, instead, patients who did not respond to biological therapy showed significantly lower plasma values of iron and taurine before starting biological anti-TNF-α treatment.

Essential Oil Molecules Can Break the Loop of Oxidative Stress in Neurodegenerative Diseases.

Essential oils (EOs) are mixtures of volatile compounds, extracted from aromatic plants, with multiple activities including antioxidant and anti-inflammatory ones. EOs are complex mixtures easy to find on the market and with low costs. In this mini narrative review, we have collected the results of in vitro and in vivo studies, which tested these EOs on validated models of neurodegeneration and in particular of the two main neurodegenerative diseases (NDs) that afflict humans: Alzheimer's and Parkinson's. Since EO compositions can vary greatly, depending on the environmental conditions, plant cultivar, and extraction methods, we focused our attention to studies involving single EO molecules, and in particular those that have demonstrated the ability to cross the blood-brain barrier. These single EO molecules, alone or in defined mixtures, could be interesting new therapies to prevent or slow down oxidative and inflammatory processes which are common mechanisms that contribute to neuronal death in all NDs.

The Bidirectional Link between Nutritional Factors and Inflammatory Bowel Diseases: Dietary Deficits, Habits, and Recommended Interventions-A Narrative Review.

Inflammatory bowel diseases comprise Crohn's disease and ulcerative colitis, two chronic inflammatory disorders of the digestive tract that develop in adolescence and early adulthood and show a rising pattern in industrialized societies, as well as in developing countries, being strongly influenced by environmental pressures such as nutrition, pollution and lifestyle behaviors. Here, we provide a narrative review of the bidirectional link between nutritional factors and IBD, of dietary deficits observed in IBD patients due to both the disease itself and dietary habits, and of the suggested nutritional interventions. Research of the literature was conducted. Clinical and basic research studies consistently demonstrate that diet could alter the risk of developing IBD in predisposed individuals. On the other hand, dietary interventions represent a valid tool in support of conventional therapies to control IBD symptoms, rebalance states of malnutrition, promote/maintain clinical remission and improve patients' quality of life. Although there are no official dietary guidelines for patients with IBD, they should receive nutritional advice and undergo oral, enteral, or parenteral nutritional supplementation if needed. However, the dietary management of malnutrition in IBD patients is complex; future clinical studies are required to standardize its management.

Spermidine-Eugenol Supplement Preserved Inflammation-Challenged Intestinal Cells by Stimulating Autophagy.

Increases in non-communicable and auto-immune diseases, with a shared etiology of defective autophagy and chronic inflammation, have motivated research both on natural products in drug discovery fields and on the interrelationship between autophagy and inflammation. Within this framework, the tolerability and protective effects of a wheat-germ spermidine (SPD) and clove eugenol (EUG) combination supplement (SUPPL) were investigated on inflammation status (after the administration of lipopolysaccharide (LPS)) and on autophagy using human Caco-2 and NCM460 cell lines. In comparison to the LPS treatment alone, the SUPPL + LPS significantly attenuated ROS levels and midkine expression in monocultures, as well as occludin expression and mucus production in reconstituted intestinal equivalents. Over a timeline of 2-4 h, the SUPPL and SUPPL + LPS treatments stimulated autophagy LC3-11 steady state expression and turnover, as well as P62 turnover. After completely blocking autophagy with dorsomorphin, inflammatory midkine was significantly reduced in the SUPPL + LPS treatment in a non-autophagy-dependent manner. After a 24 h timeline, preliminary results showed that mitophagy receptor BNIP3L expression was significantly downregulated in the SUPPL + LPS treatment compared to the LPS alone, whereas conventional autophagy protein expression was significantly higher. The SUPPL shows promise in reducing inflammation and increasing autophagy to improve intestinal health.

Dietary Habits and Nutrient Deficiencies in a Cohort of European Crohn's Disease Adult Patients.

Wrong dietary habits, such as the Western-style diet, are considered important risk factors for the development of Inflammatory Bowel Diseases (IBDs). Nevertheless, the role of dietary patterns in the clinical management of IBD patients has not been fully investigated yet. Fifty-four patients diagnosed with active Crohn's disease (CD) were enrolled and subjected to nutritional intake analysis through a weekly food diary. Nutritional patterns were analyzed, and nutrient intake was compared with those of 30 healthy subjects (HS). Blood levels of cholesterol, folic acid, minerals (K, Mg, Fe) and amino acids, were measured in CD patients to assess the presence of nutritional deficiencies. CD patients, with respect to HS, consumed significantly lower amounts of fiber, vitamins (A, E, C, B6, folic acid) and ß-carotene. Their calcium, potassium, phosphorus, iron, magnesium, copper and iodine intake were also found to be significantly lower. In blood, CD patients had significantly lower concentrations of total cholesterol, potassium, iron, and amino acids. Active CD patient diet was significantly different from those of HS and may contribute to the establishment of nutritional deficiencies. Intestinal malabsorption was evidenced in these patients. Correction of the diet with specific nutritional plans is a necessary therapeutic step for these patients. ClinicalTrials.gov: NCT02580864.

Pharmacokinetic and Permeation Studies in Rat Brain of Natural Compounds Led to Investigate Eugenol as Direct Activator of Dopamine Release in PC12 Cells.

Eugenol, cinnamaldehyde and D-limonene, the main components of natural essential oils, are endowed with antioxidant and anti-inflammatory properties which allow them to induce beneficial effects on intestinal, cardiac and neuronal levels. In order to characterize their pharmacokinetic profiles and aptitude to permeate in the central nervous system after intravenous and oral administration to rats, new analytical procedures, easily achievable with HPLC-UV techniques, were developed. The terminal half-lives of these compounds range from 12.4 ± 0.9 (D-limonene) and 23.1 ± 1.6 min (cinnamaldehyde); their oral bioavailability appears relatively poor, ranging from 4.25 ± 0.11% (eugenol) to 7.33 ± 0.37% (cinnamaldehyde). Eugenol evidences a marked aptitude to permeate in the cerebrospinal fluid (CSF) of rats following both intravenous and oral administrations, whereas cinnamaldehyde appears able to reach the CSF only after intravenous administration; limonene is totally unable to permeate in the CSF. Eugenol was therefore recruited for in vitro studies of viability and time-/dose-dependent dopamine release in neuronal differentiated PC12 cells (a recognized cellular model mimicking dopaminergic neurons), evidencing its ability to increase cell viability and to induce dopamine release according to a U-shaped time-course curve. Moreover, concentration-response data suggest that eugenol may induce beneficial effects against Parkinson's disease after oral administration.

Geraniol Treatment for Irritable Bowel Syndrome: A Double-Blind Randomized Clinical Trial.

Geraniol is an acyclic monoterpene alcohol with well-known anti-inflammatory and antimicrobial properties which has shown eubiotic activity towards gut microbiota (GM) in patients with irritable bowel syndrome (IBS). METHODS: Fifty-six IBS patients diagnosed according to Rome III criteria were enrolled in an interventional, prospective, multicentric, randomized, double-blinded, placebo-controlled trial. In the treatment arm, patients received a low-absorbable geraniol food supplement (LAGS) once daily for four weeks. RESULTS: Patients treated with LAGS showed a significant reduction in their IBS symptoms severity score (IBS-SSS) compared to the placebo (195 vs. 265, p = 0.001). The rate of responders according to IBS-SSS (reduction ≥ 50 points) was significantly higher in the geraniol vs placebo group (52.0% vs. 16.7%, p = 0.009) mainly due to the IBS mixed subtype. There were notable differences in the microbiota composition after geraniol administration, particularly a significant decrease in a genus of Ruminococcaceae, Oscillospira (p = 0.01), a decreasing trend for the Erysipelotrichaceae and Clostridiaceae families (p = 0.1), and an increasing trend for other Ruminococcaceae taxa, specifically Faecalibacterium (p = 0.09). The main circulating proinflammatory cytokines showed no differences between placebo and geraniol arms. CONCLUSION: LAGS was effective in treating overall IBS symptoms, together with an improvement in the gut microbiota profile, especially for the IBS mixed subtype.

ERα-LBD, an isoform of estrogen receptor alpha, promotes breast cancer proliferation and endocrine resistance.

Estrogen receptor alpha (ERα) drives mammary gland development and breast cancer (BC) growth through an evolutionarily conserved linkage of DNA binding and hormone activation functions. Therapeutic targeting of the hormone binding pocket is a widely utilized and successful strategy for breast cancer prevention and treatment. However, resistance to this endocrine therapy is frequently encountered and may occur through bypass or reactivation of ER-regulated transcriptional programs. We now identify the induction of an ERα isoform, ERα-LBD, that is encoded by an alternative ESR1 transcript and lacks the activation function and DNA binding domains. Despite lacking the transcriptional activity, ERα-LBD is found to promote breast cancer growth and resistance to the ERα antagonist fulvestrant. ERα-LBD is predominantly localized to the cytoplasm and mitochondria of BC cells and leads to enhanced glycolysis, respiration and stem-like features. Intriguingly, ERα-LBD expression and function does not appear to be restricted to cancers that express full length ERα but also promotes growth of triple-negative breast cancers and ERα-LBD transcript (ESR1-LBD) is also present in BC samples from both ERα(+) and ERα(-) human tumors. These findings point to ERα-LBD as a potential mediator of breast cancer progression and therapy resistance.

Wheat Germ Spermidine and Clove Eugenol in Combination Stimulate Autophagy In Vitro Showing Potential in Supporting the Immune System against Viral Infections.

Impaired autophagy, responsible for increased inflammation, constitutes a risk factor for the more severe COVID-19 outcomes. Spermidine (SPD) is a known autophagy modulator and supplementation for COVID-19 risk groups (including the elderly) is recommended. However, information on the modulatory effects of eugenol (EUG) is scarce. Therefore, the effects of SPD and EUG, both singularly and in combination, on autophagy were investigated using different cell lines (HBEpiC, SHSY5Y, HUVEC, Caco-2, L929 and U937). SPD (0.3 mM), EUG (0.2 mM) and 0.3 mM SPD + 0.2 mM EUG, significantly increased autophagy using the hallmark measure of LC3-II protein accumulation in the cell lines without cytotoxic effects. Using Caco-2 cells as a model, several crucial autophagy proteins were upregulated at all stages of autophagic flux in response to the treatments. This effect was verified by the activation/differentiation and migration of U937 monocytes in a three-dimensional reconstituted intestinal model (Caco-2, L929 and U937 cells). Comparable benefits of SPD, EUG and SPD + EUG in inducing autophagy were shown by the protection of Caco-2 and L929 cells against lipopolysaccharide-induced inflammation. SPD + EUG is an innovative dual therapy capable of stimulating autophagy and reducing inflammation in vitro and could show promise for COVID-19 risk groups.

Nutraceuticals in the Modulation of the Intestinal Microbiota: Current Status and Future Directions.

Pharmaceutical interest in the human intestinal microbiota has increased considerably, because of the increasing number of studies linking the human intestinal microbial ecology to an increasing number of non-communicable diseases. Many efforts at modulating the gut microbiota have been made using probiotics, prebiotics and recently postbiotics. However, there are other, still little-explored opportunities from a pharmaceutical point of view, which appear promising to obtain modifications of the microbiota structure and functions. This review summarizes all in vitro, in vivo and clinical studies demonstrating the possibility to positively modulate the intestinal microbiota by using probiotics, prebiotics, postbiotics, essential oils, fungus and officinal plants. For the future, clinical studies investigating the ability to impact the intestinal microbiota especially by using fungus, officinal and aromatic plants or their extracts are required. This knowledge could lead to effective microbiome modulations that might support the pharmacological therapy of most non-communicable diseases in a near future.

Dietary Habits of a Group of Children with Crohn's Disease Compared to Healthy Subjects: Assessment of Risk of Nutritional Deficiencies through a Bromatological Analysis.

Diet is a matter of interest in the pathogenesis and management of Crohn's Disease (CD). Little is known about CD children's dietary habits. Our aim was assessing the quality and the amount of nutrient intake in a group of CD pediatric patients. Data were compared with those of healthy subjects (HS). In total, 20 patients (13 males) and 48 HS (24 males) aged 4-18 years were provided with a food diary to fill out for one week. Winfood software performed the bromatological analysis, providing data about intakes of proteins and amino acids, fatty acids, carbohydrates, cholesterol, fibers, minerals, vitamins, and polyphenols. Estimates of the antioxidant activity of foods and of the dietetic protein load were also calculated. The diet of CD patients was poorer in fibers, polyphenols, vitamin A, beta-carotene, and fatty acids, and richer in animal proteins, vitamin B12, and niacin. PRAL was higher in CD patients' diets, while ORAC was higher in HS. No significant differences were observed in carbohydrate and other macro- and micronutrient consumptions. CD dietary habits seem to reflect the so-called Western diet, possibly involved in CD pathogenesis. Furthermore, analysis of dietary habits allows for prevention of nutritional deficiencies and timely correction through education and supplementation.

Antifungal Activity of Natural Compounds vs. Candida spp.: A Mixture of Cinnamaldehyde and Eugenol Shows Promising In Vitro Results.

Candida spp. are commensal organisms of the skin, mucous membranes, gastrointestinal tract, blood, and vagina of animals and humans. In recent decades, the incidence of human fungal infections has increased, with Candida spp. (mainly C. albicans) infections being the most frequent, and the treatment of fungal infections is still a clinical challenge. Colonization of the human gastrointestinal tract by Candida spp. is significant because infections (e.g., candidemia and vulvovaginal candidiasis) frequently arise from commensal microorganisms. The aim of this study was to test in vitro the antifungal activity and the eventual synergistic effect of five pure components of essential oils: cinnamaldehyde, α-pinene, limonene, eucalyptol, and eugenol. These compounds were tested on 18 Candida strains (15 C. albicans, 2 C. glabrata, and 1 C. lusitaniae) derived from a culture collection of vaginal clinical strains. METHODS: Fungistatic activity was evaluated using the disk diffusion method. For fungicidal activity, microdilution and time-kill curve protocols were set up. The checkerboard method was chosen to evaluate a possible synergistic effect of these compounds when mixed. RESULTS: Cinnamaldehyde and eugenol gave the best results, inhibiting all the Candida strains and showing a highly additive effect (FICI 0.625). The cinnamaldehyde inhibition zone (IZ), MIC, and MFC means were 69 mm, 50.05 mg/L, and 109.26 mg/L respectively. Cinnamaldehyde led to the total loss of viable Candida cells within 4 h. Eugenol IZ, MIC, and MFC means were 35.2 mm, 455.42 mg/L, and 690.09 mg/L, respectively. Eugenol led to the total loss of viable fungal cells within 1 h. Treatment with α-pinene inhibited 88.9% of Candida strains, with an IZ mean of 21.2 mm, a MIC mean of 195.41 mg/L, and a MFC mean of 251.27 mg/L; this compound led to the total loss of viable fungal cells only after 24 h. Limonene inhibited only 33.3% of the tested strains and eucalyptol did not produce an inhibition halo, so these compounds were not tested further. CONCLUSIONS: These characteristics, together with the well-known safety of cinnamaldehyde and eugenol for human use, make these two natural compounds the perfect candidates for the treatment of candidiasis. This was a pilot study, the purpose of which was to evaluate the best composition of a mixture to be used against intestinal and vulvovaginal candidiasis; in vivo studies are needed to confirm these very encouraging results.

Is the clinical pattern of pediatric celiac disease changing? A thirty-years real-life experience of an Italian center.

OBJECTIVES: Clinical presentation of pediatric celiac disease (CD) is heterogeneous and ever-evolving. Our aim is to highlight its changes throughout the years. METHODS: Data about clinical presentation of CD in children diagnosed between 1990 and 2020 at the CD Center of Maggiore Hospital, Bologna, were collected. Patients were stratified into groups based on the date [P1 (1990-2011), P2 (2012-2020)] and age [G1 (< 2 years), G2 (2-5), G3 (6-11), G4 (12-18)] at diagnosis, then investigated by comparing CD clinical presentation in different periods and ages. RESULTS: 1081 children were selected. Mean age at diagnosis increases from 5.9 to 6.6 years from P1 to P2. Gastrointestinal Symptoms (GIs) are predominant, with a decline of diarrhea (47%VS30%) and an increase of constipation (4%VS19%) (p < 0.001). Among Extraintestinal symptoms (EIs) a decrease of anemia (76%VS43%, p = 0,001) is observed. Failure to Thrive (FTT) is stable throughout the years (p = 0.03), while screenings show a trend of increment (19%VS23%). GIs' frequency decline from G1 to G4 (p = 0,001), with reduction of diarrhea (p < 0.001), and rise of recurrent abdominal pain (p = 0,02). EIs are more frequent at older ages, FTT in younger patients. CONCLUSIONS: Changes in clinical presentation of CD have occurred in the last 30 years. We observe a reduction of severe and classic gastroenterologic symptoms and a rise of atypical ones, together with a growth of serological screenings and higher age at diagnosis. Awareness about CD clinical trends is crucial for a proper approach and early diagnosis.

Effect of a Fiber D-Limonene-Enriched Food Supplement on Intestinal Microbiota and Metabolic Parameters of Mice on a High-Fat Diet.

Several studies showed that D-Limonene can improve metabolic parameters of obese mice via various mechanisms, including intestinal microbiota modulation. Nevertheless, its effective doses often overcome the acceptable daily intake, rising concerns about toxicity. In this study we administered to C57BL/6 mice for 84 days a food supplement based on D-Limonene, adsorbed on dietary fibers (FLS), not able to reach the bloodstream, to counteract the metabolic effects of a high-fat diet (HFD). Results showed that daily administration of D-Limonene (30 and 60 mg/kg body weight) for 84 days decreased the weight gain of HFD mice. After 84 days we observed a statistically significant difference in weight gain in the group of mice receiving the higher dose of FLS compared to HFD mice (35.24 ± 4.56 g vs. 40.79 ± 3.28 g, p < 0.05). Moreover, FLS at both doses tested was capable of lowering triglyceridemia and also fasting glycemia at the higher dose. Some insights on the relevant fatty acid changes in hepatic tissues were obtained, highlighting the increased polyunsaturated fatty acid (PUFA) levels even at the lowest dose. FLS was also able to positively modulate the gut microbiota and prevent HFD-associated liver steatosis in a dose-dependent manner. These results demonstrate that FLS at these doses can be considered non-toxic and could be an effective tool to counteract diet-induced obesity and ameliorate metabolic profile in mice.

Multiunit In Vitro Colon Model for the Evaluation of Prebiotic Potential of a Fiber Plus D-Limonene Food Supplement.

The search for new fiber supplements that can claim to be "prebiotic" is expanding fast, as the role of prebiotics and intestinal microbiota in well-being has been well established. This work explored the prebiotic potential of a novel fiber plus D-Limonene supplement (FLS) in comparison to fructooligosaccharides (FOS) over distal colonic fermentation with the in vitro model MICODE (multi-unit in vitro colon gut model). During fermentation, volatilome characterization and core microbiota quantifications were performed, then correlations among volatiles and microbes were interpreted. The results indicated that FLS generated positive effects on the host gut model, determining: (i) eubiosis; (ii) increased abundance of beneficial bacteria, as Bifidobacteriaceae; (iii) production of beneficial compounds, as n-Decanoic acid; (iv) reduction in detrimental bacteria, as Enterobaceteriaceae; (v) reduction in detrimental compounds, as skatole. The approach that we followed permitted us to describe the prebiotic potential of FLS and its ability to steadily maintain the metabolism of colon microbiota over time. This aspect is two-faced and should be investigated further because if a fast microbial turnover and production of beneficial compounds is a hallmark of a prebiotic, the ability to reduce microbiota changes and to reduce imbalances in the productions of microbial metabolites could be an added value to FLS. In fact, it has been recently demonstrated that these aspects could serve as an adjuvant in metabolic disorders and cognitive decline.

Complementary Feeding in Italy: From Tradition to Innovation.

Complementary feeding (CF) is a pivotal phase of the individual's growth, during which children develops their future dietary habits. To date, only few studies investigated and compared weaning modalities between different geographical areas. The aim of this article is to describe the current Italian practice for CF in healthy term infants among different areas (North, Center, South) of Italy. Two different multiple-choice questionnaires were produced and sent to 665 Italian primary care pediatricians (PCP) and 2023 families with children under 1 year of age. As emerged from our investigation, in Italy CF is usually started between the 5th and 6th month of life. The preferred approach (chosen by 77% of families) involves the use of home-cooked liquid or semi-liquid ailments, or industrial baby foods. A new CF modality is emerging, consisting of traditional complementary foods with adult food tastings (10% of families). Approximately 91% of pediatricians give written dietary suggestions, and 83% of families follow their advice. We found significantly divergent weaning habits among different areas of Italy. PCP have a key role in guiding parents during the introduction of new foods in their infant's diet and should take this as an opportunity to educate the whole family to healthy dietary habits.

Comparing effects and action mechanisms of BPA and BPS on HTR-8/SVneo placental cells†.

Bisphenol A (BPA) is one of the most investigated compound as a suspected endocrine disrupting chemical. It has been found at nM concentrations in the maternal serum, cord serum, and amniotic fluid and also permeates placental tissues. Attempts are being made to replace BPA with the analog Bisphenol S (BPS). Also BPS was found in maternal and umbilical cord serum, and urine samples from a large population of pregnant women. A few studies investigated BPA impact on the placentation process, and even less are available for BPS. This work aimed to elucidate and compare the effects of BPA and BPS on physiological functions of HTR-8/SVneo cells, derived from extravillous trophoblast of first-trimester pregnancy. Proliferation and migration ability of trophoblast cells were assessed in vitro after exposure to BPA or BPS (10-13-10-3 M). Further, induction of the inflammatory response by the bisphenols was studied. To provide insight into the molecular pathways implicated in the responses, experiments were carried out in the presence or absence of tamoxifen as estrogen receptors (ERs) blocker, and U0126 as ERK1/2 phosphorylation inhibitor. Data indicate that BPA significantly affects both proliferation and migration of HTR-8/SVneo cells, through ER and ERK1/2 mediated processes. Differently, BPS only acts on proliferation, again through ER and ERK1/2 mediated processes. BPS, but not BPA, induces secretion of interleukins 6 and 8. Such effect is inhibited by blocking ERK1/2 phosphorylation. To the best of our knowledge, these are the first data showing that BPS affects trophoblast functions through ER/MAPK modulation.

Molecules Present in Plant Essential Oils for Prevention and Treatment of Colorectal Cancer (CRC).

Essential oils (EOs) are a complex mixture of hydrophobic and volatile compounds synthesized from aromatic plants, commonly present in the human diet. In recent years, many in vitro studies have suggested possible anticancer properties of single EO compounds, on colorectal cancer (CRC) cells. However, the majority of these studies did not compare the effects of these compounds on normal and cancer colon cells. By using NCM-460, a normal human mucosal epithelial cell line, Caco-2, a human colon epithelial adenocarcinoma cell line, and SW-620, colon cancer cells derived from lymph node metastatic site, we identified cinnamaldehyde, derived from cinnamon EO and eugenol, derived from bud clove EO, as compounds with a specific anticancer action selectively targeting the transformed colonic cells. Both cinnamaldehyde (75 µM) and eugenol (800 µM), after 72 h of treatment, were capable to induce apoptosis, necrosis and a cell cycle slowdown in Caco-2 and in SW-620, but not in NCM-460 cells. If associated with a targeted delivery to the colon, these two compounds could prove effective in the prevention or treatment of CRC.