IL-12 and IL-23 are important pro-inflammatory cytokines in intestinal inflammation, mainly produced by antigen-presenting cells. IL-12 is composed of the p35 and p40 subunits, and IL-23 is composed of the p40 and p19 subunits. Preclinical studies have suggested that IL-12 and IL-23 are involved in the pathophysiological process of IBD and play a role in the induction and maintenance of intestinal inflammation ( 82). In addition, genomic studies have shown an association between the IL-12/IL-23 pathway and CD ( 83). Multiple studies have suggested that IL-12/23 and IL-23 antagonists are potential therapeutic options for IBD treatment. Experts recommended IL-12/23 and IL-23 antagonists as a first- or second-line therapy because of their efficacy in biologic-naïve and experienced patients ( 90). Anti-integrin Therapy Chicco F, Magrì S, Cingolani A, et al. Multidimensional Impact of Mediterranean Diet on IBD Patients. Inflamm Bowel Dis 2020:27(1):1-9. Doi:10.1093/ibd/izaa097.

B6, B1, A, B2, folic acid, K, biotin, D, B12) and choline bitartrate. MODULEN® (400 g powder) Nutrition Information Serve size: 50 g (made up volume 250 ml) Serves per container: 8Nutrient Units Per serve Per 100 mlEnergy kJ / kcal 1037 / 250 415 / 100Protein (14% kcal) g 9.0 3.6Carbohydrate (44% kcal) of which: g 27 10.8- Sugars g 10.5 4.2Fat (42% kcal) of which: g 11.5 4.6- Saturated g 6.6 2.6- Monounsaturated fatty acids g 2.0 0.78- Polyunsaturated fatty acids g 1.2 0.48- MCT g 3.0 1.2Fibre (0% kcal) g 0 0Sodium mg 85 34VitaminsBiotin μg 8.0 3.2Folic acid μg 60 24Niacin mg 2.9 1.2mg NE 4.9 2.0Pantothenic acid mg 1.2 0.48Vitamin A μg 210 84Vitamin B1 mg 0.29 0.12Vitamin B2 mg 0.32 0.13Vitamin B6 mg 0.41 0.16Vitamin B12 μg 0.80 0.32Vitamin C mg 23 9.2Vitamin D μg 2.5 1.0Vitamin E mg TE 3.3 1.3Vitamin K μg 13 5.2MineralsCalcium mg 222 89Chloride mg 182 73Chromium μg 12 4.8Copper mg 0.24 0.10Iodine μg 24 10Iron mg 2.7 1.1Magnesium mg 50 20Manganese mg 0.49 0.20Molybdenum μg 18 7.2Phosphorus mg 150 60Potassium mg 300 120Selenium μg 8.5 3.4Zinc mg 2.3 0.92Other NutrientsCholine mg 17 6.8 Modulen (400g powder) The Modulen ® formula is casein-based. This protein is significant, since it can protect TGF-β2 from duodenal enzymatic degradation [ 7]. Potential beneficial effects may be due to the whole protein or to its derived peptides ( Figure 1, right panel). In an ileitis model, macroscopic and microscopic lesions, and Goblet cell depletion were protected by β-casofensin [ 46]. The amino acid profile of casein proteins is principally rich in two essential amino acids and one non-essential [ 47]. The first one is leucine (from 69 to 108 mg/g), which promotes cryptidin-1 production by Paneth cells via Slc7a8 transporter [ 48]. The second one is lysine (from 49 to 67 mg/g), which has anti-inflammatory properties as demonstrated by the reduction of weight loss, disease index, and inflammatory cytokines in dextran sulfate sodium (DSS) induced colitis [ 49]. Finally, glutamic acid presents the highest concentration (from 218 to 239 mg/g). This amino acid has been widely studied in the intestine and it is recognized as a principal actor in intestinal integrity ( Figure 1, right panel). Not only glutamic acid can regulate proliferative, apoptotic, and inflammatory cellular pathways, but also tight junction proteins [ 50]. Glutamic acid can act directly on proteins such as ERK1/2, STAT, and HSF, and indirectly by enhancing growth factors’ effects like EGF and TGF-α ( Figure 1, right panel).Contains Transforming Growth Factor –ß2 (TGF-ß2) from patented manufacturing process. TGF-ß2 has natural anti-inflammatory properties to reduce inflammation associated with inflammatory bowel disease In this review, we not only focus on drugs and therapies that have been approved, but also focus on the potential methods for the treatment of IBD, providing a comprehensive overview for clinicians of available therapies and drugs for IBD treatment.

Clinical studies using Modulen IBD® as PEN show that CDED + PEN was as effective as the current EEN standard in achieving remission, but the CDED + PEN was better tolerated and superior for sustaining remission. Another important role for enteral nutrition is in the perioperative setting, to help improve surgical outcomes for patients with IBD. In these studies, a diet of EEN prior to surgery can be associated with improved nutritional status, reduced length of surgery, and lower rate of complications such as infection.

Footnotes

Scarallo L et al., Crohn’s Disease Exclusion Diet in children with Crohn’s disease: a case series. CMRO. 2021, Volume 37, Issue 5. A 2019 randomized control study, first presented at ECCO, has helped to establish the general principles of the CDED. 23 Group 3 (UCED alone) showed the highest rate of clinical remission (40%) and endoscopic remission (27%). Group 3 also demonstrated a significant decrease in the Simple Clinical Colitis Activity Index (SCCAI) at week 8. A significant proportion of patients worsened after FT (Group 1 or Group 2) by week 8 compared to baseline. Group 3 reported the least worsening of disease. The therapeutic efficacy of aminosalicylic acid preparations for CD remains controversial. A review has suggested that oral 5-ASA preparations have no significant advantage in maintaining remission in patients with CD ( 17). However, a retrospective study in the UK found that 5-ASA was widely used as a long-term treatment for CD as about a quarter of patients continued to use 5-ASA for more than 10 years ( 18). 5-ASA therapy for more than a year could reduce the consumption of related medical resources (including referrals, hospitalization, and surgery) ( 18). Gjuladin-Hellon et al. have reported the benefit of 5-ASA in preventing relapse of CD in remission after surgery ( 19). Coward et al. in their Bayesian network meta-analysis found that high-dose mesalamine is an option for inducing remission among mild-to-moderate CD patients preferring to avoid steroids ( 20). Other studies have also reported the treatment effectiveness of aminosalicylates in CD ( 21, 22). Suskind DL, Lee D, Kim YM, Wahbeh G, Singh N, Braly K, Nuding M, Nicora CD, Purvine SO, Lipton MS, Jansson JK, Nelson WC. The Specific Carbohydrate Diet and Diet Modification as Induction Therapy for Pediatric Crohn's Disease: A Randomized Diet Controlled Trial. Nutrients. 2020 Dec 6;12(12):3749. doi: 10.3390/nu12123749.

sirop de glucoză, cazeină ( lapte), sucroză, grăsimi din lapte, ulei vegetal de cocos, minerale (citrat de potasiu, fosfat de calciu, citrat de sodiu, carbonat de calciu, clorură de magneziu, hidroxid de potasiu, clorură de potasiu, sulfat feros, sulfat de zinc, oxid de magneziu, sulfat de mangan, sulfat de cupru, molibdat de sodiu, iodură de potasiu, clorura de crom, selenat de sodiu), ulei vegetal de porumb, emulgator (lecitine) (conține soia), vitamine [ascorbat de sodiu (vitamina C), acetat de DL-alfa-tocoferil (vitamina E), niacina, adic pantotenic, clorhidrat de piridoxina (vitamina B6), mononitrat de tiamină (vitamina B1), acetat de retinil (vitamina A), riboflavina (vitamina B2), acid folic, filochinona (vitamina K1), biotina, colecalciferol (vitamina D3), cianocobalamină (vitamina B12)], bitartrat de colină. None of the therapies were effective for the most severe patients (SCCAI >9). Only one out of 28 biologic refractory patients achieved clinical remission.Svolos V, Hansen R, Nichols B, Quince C, Ijaz UZ, Papadopoulou RT, Edwards CA, Watson D, Alghamdi A, Brejnrod A, Ansalone C, Duncan H, Gervais L, Tayler R, Salmond J, Bolognini D, Klopfleisch R, Gaya DR, Milling S, Russell RK, Gerasimidis K. Treatment of Active Crohn's Disease With an Ordinary Food-based Diet That Replicates Exclusive Enteral Nutrition. Gastroenterology. 2019 Apr;156(5):1354-1367.e6. doi: 10.1053/j.gastro.2018.12.002. Epub 2018 Dec 11. Dietary management of CD has been documented, but we know that what works for CD does not necessarily work for UC. 27 Specific Carbohydrate Diet™ (SCD) includes fruits, vegetables, fish, meat, homemade yogurt, and aged cheeses, and excludes grains, processed foods, soy, and certain vegetables such as potatoes and corns. The SCD has been suggested to decrease symptoms in people with mild to moderate Crohn's disease.

For patients with mild to moderate Crohn's disease, the Mediterranean Diet has been shown to be just as effective as the Specific Carbohydrate Diet™ in reducing symptoms and improving overall quality of life. The Low FODMAP Diet was originally developed for people with irritable bowel syndrome (IBS) as a way to reduce symptoms, but has also been shown to reduce symptoms in people with inflammatory bowel disease (IBD) who have overlapping IBS. However, the Low FODMAP diet has not been shown to reduce inflammation. Bischoff S, Bager P, et al. ESPEN guideline on clinical nutrition in inflammatory bowel disease. Clinical Nutrition. 2023 March; 42(3) 352-379. The exact cause of IBD remains indistinct, but it is generally accepted that its etiopathology is multifactorial, involving genetic predisposition, mucosal barrier dysfunction, disturbances in the gastrointestinal microbiota, dysregulated immune responses, environmental, and lifestyle factors ( 3, 4).

Crohn’s disease (CD) and ulcerative colitis (UC) are chronic intestinal inflammatory diseases of unknown aetiology, characterized by a recurrent inflammatory condition. The pathophysiology is multifactorial and complex, involving an inappropriate immune activation of the gut mucosa in genetically susceptible individuals, triggered by an altered composition of the gut microbiota. The incidence of inflammatory bowel disease (IBD) has increased worldwide in developed nations and more recently in developing countries. 1, 2 This rapid increase in the incidence of IBD over the last half-century, particularly in developing countries, clearly points to the role of changing environmental factors intrinsically implicated in disease development. 1 Genes cannot change within such a short time frame, thus disease susceptibility remains almost identical over several generations. The differing role of genetics and the environment in disease development is clearly reflected by epidemiological data on immigrants from low- to high-IBD-incidence regions: where, the second generation of immigrants has the same risk of developing IBD as the local population living for generations in the same area. 3 A western lifestyle, including changes in dietary habits, urbanization and industrialization, has been proposed as one explanation for this worldwide increase in IBD. 4 The study showed that CDED plus PEN was better tolerated than exclusive enteral nutrition (EEN) in children with mild to moderate CD. The combination of CDED plus PEN induced sustained remission in a significantly higher proportion of patients than EEN and produced changes in the fecal microbiome associated with remission. Yanai et al., The Crohn’s disease exclusion diet for induction and maintenance of remission in adults with mild-to- moderate Crohn’s disease (CDED-AD): an open-label, pilot, randomized trial. Lancet Gastroenterol Hepatol. 2022;7:49-59.