Amalia Di Petrillo

Background and aim: Crohn’s disease (CD) is a chronic inflammatory disorder of the gastrointestinal tract resulting from a complex interplay among genetic susceptibility, immune dysregulation, environmental factors, and alterations in the gut microbiota. Among these, diet has emerged as a key modifiable factor influencing intestinal inflammation, barrier integrity, and disease progression. This review aims to critically evaluate the role of dietary patterns and food additives in the pathogenesis and management of Crohn’s disease, with particular emphasis on their effects on intestinal inflammation, epithelial barrier function, and host–microbiota interactions. Methods: A comprehensive literature search was conducted using the PubMed, Scopus, and Web of Science databases up to March 2026. Clinical trials, observational studies, and mechanistic research were included based on their relevance to dietary factors, food additives, and intestinal inflammation in CD. Evidence was synthesized narratively to integrate clinical and experimental findings. Results: Dietary interventions such as the Crohn’s disease exclusion diet (CDED), specific carbohydrate diet (SCD), low-FODMAP diet, and Mediterranean diet (MD) demonstrate varying degrees of efficacy in improving clinical symptoms and, in some cases, inflammatory markers. In contrast, high consumption of ultra-processed foods is consistently associated with increased disease risk and activity. Emerging evidence highlights the role of food additives—particularly emulsifiers and artificial sweeteners—in disrupting gut barrier integrity, promoting dysbiosis, and enhancing inflammatory responses. Recent human studies further suggest that exposure to these compounds may correlate with disease activity, supporting their potential role in CD pathophysiology. Conclusions: Diet plays a significant adjunctive role in the management of Crohn’s disease. Reducing exposure to ultra-processed foods and potentially harmful food additives, while promoting balanced dietary patterns, may improve clinical outcomes. Further research is needed to clarify long-term effects and to develop personalized, evidence-based nutritional strategies for patients with CD.

Background/Objectives: Ustekinumab, targeting the shared p40 subunit of interleukin (IL)-12 and IL-23, is an effective therapy for Crohn’s disease (CD), yet reliable predictors of response remain lacking. Given the central role of the IL-12/IL-23 axis in intestinal inflammation, we aimed to characterize the baseline mucosal expression of IL-12/IL-23 pathway components in lamina propria immune cells, and to explore their association with clinical response and remission following ustekinumab therapy. Methods: In this prospective, single-center study, biopsy-derived lamina propria mononuclear cells (LPMCs) were obtained from patients with CD prior to ustekinumab initiation. Gene expression of IL-12/IL-23 cytokine subunits and receptors was assessed by quantitative real-time PCR. Flow cytometry was performed to evaluate the distribution of T helper and innate lymphoid cell subsets and the expression of IL-23R and IL-12Rβ2. Clinical outcomes were assessed at week 16. Results: Fifteen consecutive patients were enrolled and included in the study. At week 16, 14/15 (93.3%) and 9/15 (60.0%) of patients reached clinical response and remission, respectively. No statistically significant differences in baseline mucosal gene expression of IL-12/IL-23 pathway components were observed between remitters and non-remitters. A trend toward higher expression of receptor subunits (IL23R, IL12RB1, IL12RB2) was observed in remitters, albeit with high variability and overlapping distributions. Similarly, cytokine subunits (IL23p19, IL12/IL23p40, IL12p35) showed no consistent differential expression pattern between the groups. In contrast, flow cytometry revealed a significantly higher frequency of IL-23R-expressing Th1 cells in remitters compared with non-remitters (20.6% vs. 6.8%, p = 0.009). Conclusions: Baseline transcriptional profiling of IL-12/IL-23 pathway components was not associated with remission following ustekinumab therapy. However, increased expression of IL-23R on mucosal Th1 cells identified a distinct immunological signature associated with clinical remission, suggesting that IL-23R expression on mucosal Th1 cells may represent a promising candidate biomarker that requires validation in larger independent cohorts.

Background: Malnutrition is frequently under-investigated during remission in patients with Inflammatory Bowel Disease (IBD), despite its significant impact on clinical outcomes and quality of life. This study aimed to evaluate the increase in diagnostic performance of five nutritional screening tools (NSTs) when serially administered to IBD outpatients in sustained clinical remission. Methods: In this prospective, single-center cohort study, NSTs were administered, and body composition analysis was performed in IBD patients at baseline and after six months. At both time points, the sensitivity, specificity, predictive values, and accuracy of NSTs in detecting malnutrition and persistent malnutrition per ESPEN and GLIM criteria were evaluated, comparing repeated to single-point assessments. A sensitivity analysis using low FFMI as a reference was also performed. Results: Sixty-six IBD patients (32 Crohn’s disease; 34 ulcerative colitis) were enrolled. At baseline, 25.7% and 9% of patients were malnourished according to ESPEN and GLIM criteria, respectively, with 7.5% exhibiting low FFMI. Malnutrition prevalence increased over time to 53%, 16.6%, and 16.6%, respectively. Among NSTs, MUST and SaskIBD-NR consistently exhibited the highest specificity for malnutrition detection at baseline, at 6 months, and for persistent malnutrition for ESPEN, GLIM and low FFMI. Serial (repeated) NST administration markedly improved the specificity of all tools, compared to single-point assessments. Conclusions: Serial nutritional screening with MUST or SaskIBD-NR significantly enhances the specificity of malnutrition risk detection in IBD patients in remission, supporting the incorporation of repeated nutritional assessments into clinical practice to offer a practical strategy to enhance screening effectiveness in IBD outpatient care.

This study examines the antidiabetic potential of Rubus ulmifolius, a shrub traditionally used for medicinal and nutritional purposes. The aim was to assess the fruit extract’s inhibitory effect on α-amylase and α-glucosidase, therapeutic targets in type 2 diabetes (T2D), given their role in carbohydrate digestion. Considering the role of islet amyloid polypeptide (IAPP) aggregation in pancreatic β-cell dysfunction in T2D, the extract’s effect on inhibiting this process was also evaluated. Cytocompatibility and antioxidant effects were tested in Caco-2 cells, while caspase-1 activity was measured to evaluate anti-inflammatory potential. Phytochemical analysis of R. ulmifolius fruits revealed various phenolic compounds, with anthocyanin as the most abundant one. The cyanidin-3-O-glucoside accounted for 86% of all anthocyanins. Among flavonoids, the most represented ones were quercetin-HMG-glucoside and a kaempferol derivative, while ellagic acid glucuronide was the predominant ellagitannin. The extract showed significantly higher α-glucosidase inhibition with an IC₅₀ value of 2.8 µg/mL, 32 times more effective than acarbose, and it markedly inhibited IAPP aggregation in a dose-dependent manner. It demonstrated antioxidant activity in cellular and acellular systems, without cytotoxicity. Caspase-1 activity was also reduced in intestinal cells. These findings support R. ulmifolius fruits as a promising functional food for managing T2D and preserving pancreatic function.

Importance and Objective: Xanthine oxidase (XO) plays a key role in purine metabolism, catalyzing the oxidation of hypoxanthine to xanthine, and xanthine to uric acid (UA) with the production of superoxide anions. The accumulation of UA has been shown to initiate the inflammatory process through NLRP3 inflammasome, and the production of reactive oxygen species (ROS) contributes to inflammation-related tissue damage in different organs. This study aimed to investigate the role of XO in the pathogenesis of Inflammatory Bowel Disease (IBD) and the anti-inflammatory potential of XO inhibition. Design: XO expression and activity were assessed in the mucosa of moderately-to-severely active ulcerative colitis (UC) and Crohn’s disease (CD) patients. The functional role of XO, the activation of NLRP3 inflammasome, and the expression of proinflammatory cytokines were investigated in ex vivo intestinal organ cultures in the presence or absence of XO inhibitors. Results: In silico and in vitro analysis showed that XO mRNA and protein expression were upregulated in the UC and CD intestinal mucosa compared to controls. XO overexpression in the inflamed mucosa was associated with increased enzymatic activity, accumulation of UA and functionally linked to NLRP3-dependent IL1beta and IL18 expression. Accordingly, XO inhibitors, Allopurinol and Febuxostat, prevented NLRP3 activation, reduced Caspase1 activity and IL1beta and IL18 expression in ex vivo organ cultures of inflamed intestinal mucosa from both UC and CD patients. Conclusions and Relevance: Overexpression of XO in IBD might contribute to inflammation by promoting NLRP3 inflammasome activation and proinflammatory cytokine production.

Inflammatory bowel disease (IBD) is characterized by chronic inflammation of the gastrointestinal tract. Although the aetiology of IBD remains largely unknown, several studies suggest that an individual’s genetic susceptibility, external environmental factors, intestinal microbial flora, and immune responses are all factors involved in and functionally linked to the pathogenesis of IBD. Beyond the gastrointestinal manifestations, IBD patients frequently suffer from psychiatric comorbidities, particularly depression and anxiety. It remains unclear whether these disorders arise solely from reduced quality of life or whether they share overlapping biological mechanisms with IBD. This review aims to explore the bidirectional relationship between IBD and depressive disorders (DDs), with a focus on four key shared mechanisms: immune dysregulation, genetic susceptibility, alterations in gut microbiota composition, and dysfunction of the hypothalamic–pituitary–adrenal (HPA) axis. By examining recent literature, we highlight how these interconnected systems may contribute to both intestinal inflammation and mood disturbances. Furthermore, we discuss the reciprocal pharmacologic interactions between IBD and DDs: treatments for IBD, such as TNF-alpha and integrin inhibitors, have demonstrated effects on mood and anxiety symptoms, while certain antidepressants appear to exert independent anti-inflammatory properties, potentially reducing the risk or severity of IBD. Overall, this review underscores the need for a multidisciplinary approach to the care of IBD patients, integrating psychological and gastroenterological assessment. A better understanding of the shared pathophysiology may help refine therapeutic strategies and support the development of personalized, gut–brain-targeted interventions.

Background: Colonoscopy is crucial for diagnosing and monitoring inflammatory bowel disease (IBD), assessing disease activity, and detecting dysplasia. However, patient adherence to surveillance remains suboptimal due to discomfort, anxiety, and concerns about bowel preparation. Methods: This multicenter cross-sectional study assessed patient satisfaction with colonoscopy in IBD patients across three Italian centers. Participants completed pre- and post-examination questionnaires, including the Endoscopy Customer Satisfaction Questionnaire (ECSQ) and Perceived Stress Scale (PSS-10). Clinical factors, bowel preparation methods, and healthcare provider expertise were analyzed. Results: Among 444 enrolled patients, overall satisfaction was high (98.8%) but varied across procedural phases. Higher satisfaction was predicted by expert endoscopists (β = 2.11, p = 0.012), disease remission (β = 1.70, p = 0.020), and frequent endoscopic procedures in the last 24 months (β = 0.46, p = 0.041). Conversely, severe disease activity (β = −3.87, p < 0.001) was associated with lower satisfaction. Deep sedation and high-volume bowel preparation negatively impacted satisfaction. Conclusions: Optimizing bowel preparation, enhancing healthcare provider expertise, and implementing stress-reducing strategies could improve patient adherence to surveillance guidelines in IBD care.

Type 2 diabetes (T2D), characterized by insulin resistance and β-cell dysfunction, requires continuous advancements in management strategies, particularly in controlling postprandial hyperglycemia to prevent complications. Current antidiabetics, which have α-amylase and α-glucosidase inhibitory activities, have side effects, prompting the search for better alternatives. In addition, diabetes patients are particularly vulnerable to yeast infections because an unusual sugar concentration promotes the growth of Candida spp. in areas like the mouth and genitalia. Asphodelus microcarpus contains bioactive flavonoids with potential enzyme inhibitory properties. This study investigates α-amylase and α-glucosidase inhibitory activities and antioxidant and antimycotic capacity of ethanolic extracts from different parts of A. microcarpus. Results show that extracts significantly inhibit α-glucosidase, with the IC₅₀ value being up to 25 times higher than for acarbose, while exerting low α-amylase activity. The extracts also demonstrated strong antioxidant properties and low cytotoxicity. The presence of phenolic compounds is likely responsible for the observed biological activities. Molecular docking analysis of 11 selected compounds identified emodin and luteolin as significant inhibitors of α-glucosidase. Additionally, the extracts demonstrated significant antibiofilm action against an MDR strain of Candida albicans. These findings suggest that A. microcarpus is a promising source of natural compounds for T2D management.

Pistacia lentiscus L. (P. lentiscus) is an evergreen shrub (Anacardiaceae family) primarily found in the Mediterranean region. The plant has been thoroughly characterized, resulting in a high concentration of bioactive compounds as flavonoids and phenolics. Moreover, P. lentiscus was revealed to possess a great nutritional and industrial importance because of its variety of biological activities, including antibacterial, anti-inflammatory, anti-atherogenic and antioxidant properties. Many of its beneficial health properties and applications date back to antiquity, and the European Medicines Agency officially acknowledged it as an herbal medicinal product. Indeed, it is widely employed in conventional medicine to treat several diseases, including type 2 diabetes (T2D). On this basis, this review aims to summarize and describe the chemical composition of different parts of the plant and highlight the potential of P. lentiscus, focusing on its antidiabetic activities. The plant kingdom is drawing increasing attention because of its complexity of natural molecules in the research of novel bioactive compounds for drug development. In this context, P. lentiscus demonstrated several in vitro and in vivo antidiabetic effects, acting upon many therapeutic T2D targets. Therefore, the information available in this review highlighted the multitarget effects of P. lentiscus and its great potential in T2D treatment.