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. Suskind DL, Cohen SA, Brittnacher MJ, Wahbeh G, Lee D, Shaffer ML, Braly K, Hayden HS, Klein J, Gold B, Giefer M, Stallworth A, Miller SI. Clinical and Fecal Microbial Changes With Diet Therapy in Active Inflammatory Bowel Disease. J Clin Gastroenterol. 2018 Feb;52(2):155-163. doi: 10.1097/MCG.0000000000000772.

Patients often attribute the clinical symptoms of IBD to their diet. Several studies have provided information on patients’ perceptions of symptoms as related to their dietary intake. In a self-reported survey of a large cohort of IBD patients, Cohen and colleagues 72 found that dietary patterns differed based on IBD subtype and history of surgery, but the foods that were perceived to either worsen or improve symptoms were consistent across all groups. Yogurt and rice were found to improve symptoms within all groups of patients while bananas were found to more frequently improve symptoms in those patients with a total colectomy and an ileal pouch. The foods that worsened symptoms in most groups were as follows: nonleafy vegetables, spicy foods, fruit, nuts, leafy vegetables, fried foods, milk, red meat, soda, popcorn, dairy, alcohol, high-fibre foods, corn-based fatty foods, seeds, coffee, and beans. 72 As expected, patients tended to avoid foods that they reported as worsening their symptoms.MRI showed 5–10 cm patchy ileocecal inflammation (ICV). Colonoscopy showed deep ulcers in ICV. The patient had previously demonstrated loss of response to infliximab, adalimumab and azathioprine, and was being treated with ustekinumab weekly.

Nikolaus S, Schreiber S. Diagnostics of inflammatory bowel disease. Gastroenterology. 2007 Nov; 133(5):1670-89. https://www.fda.gov/regulatory-information/search-fda-guidance-documents/enforcement-policy-regarding-investigational-new-drug-requirements-use-fecal-microbiota-0 Khalili H, et al. Adherence to a Mediterranean diet is associated with a lower risk of later-onset Crohn's disease: results from two large prospective cohort studies. Gut. 2020 Sep;69(9):1637-1644. The diet emphasizes components that offer a protective effect, including fruit and vegetable fibers, pectin and resistant starch, and tryptophan. UCED has some important distinctions from the CDED:

However, TPs have many adverse side effects, such as bone marrow suppression ( 50), liver injury ( 51), and gastrointestinal intolerance ( 44), etc. It has been reported that up to 39% of patients with IBD discontinue using TPs due to adverse reactions, most of which occur within 3 months of treatment ( 44). The use of TPs in IBD treatment has declined due to concerns about adverse drug reactions. MTX TNF-α is a prototypic member of a large family of cytokines that play important roles in inflammation, apoptosis, proliferation, invasion, etc. ( 71) Overexpression of TNF-α can cause chronic inflammation and lead to autoimmune diseases and tissue damage. Anti-TNF-α monoclonal antibodies, such as Infliximab (IFX) and Adalimumab (ADA), exert therapeutic effects by inhibiting TNF-α-associated inflammatory responses and tissue damage.

CSs may be a kind of treatment selection for patients with UC who have not responded to mesalazine within 2–4 weeks, and those with mild-to-moderate CD, especially with extensive lesions ( 28). CSs have no proven efficacy in maintaining remission in IBD and should not be used for this purpose. Systemic oral CSs may result in numerous side effects, such as opportunistic infections, diabetes mellitus, hypertension, ocular effects, venous thromboembolism (VTE), osteoporosis, etc ( 29, 30). Steroid dependency or excess was found in ~15–40% of IBD patients ( 31, 32). Further investigation should define appropriate corticosteroid use and find measures for the improvement in CSs prescription management. 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. This set of work has paved the way towards a new question: Can IBD be treated with diets? Recent studies 15,16,17,18,19 have providedevidence that this could be the case. Alongside other diets, the Crohn’s Disease Exclusion Diet (CDED) has been shown in an RCT and through real-world clinical evidence to be effective in inducing remission in children with mild to moderate CD, and may support maintenance of remission. 20 Levine A, Rhodes JM, Lindsay JO, et al. Dietary Guidance From the International Organization for the Study of Inflammatory Bowel Diseases. Clinical Gastroenterology and Hepatology: the Official Clinical Practice Journal of the American Gastroenterological Association 2020:18(6):1381-92. Doi:10.1016/j.cgh.2020.01.046. A 2021 prospective study in adults 24 treated 32 patients with mild to severe CD. Patients were seen at baseline, at week 6, and at week 12. At week 6 there was a 76.7% clinical remission rate. Remission rose to 82.1% at 12 weeks.The effects of nutrition and diet on the host are multiple: food ingredients can directly interact with epithelial cells or under certain conditions with the immune system, as well as indirectly via gut microbiota. Gut microbiota form a complex and dynamic system with a steady state, which can be perturbed by many environmental factors, including diet. A homeostatic balance of the host–bacteria relationship is important and vital for a normal health process. An imbalanced intestinal microbiota termed ‘dysbiosis’ has been repeatedly seen in IBD and is now recognized as a key factor in gut inflammation. 12 Sokol and colleagues 13 showed a significant decrease in the proportion of the Clostridium leptum phylogenetic group in patients with colonic CD. These results were confirmed by a metagenomic approach, revealing a restriction in biodiversity depending on bacteria belonging to the Firmicutes phylum ( C. leptum and Clostridium coccoides) with a decrease in the proportion of bacteria belonging to the C. leptum phylogenetic group. 14, 15 This dysbiosis is characterized by a high instability of the microbiota over time, the presence of approximately 30% of unusual bacteria, a marked increase in mucosal bacterial concentration, and a restriction in biodiversity regarding the Firmicutes phylum. Within this group, a decrease in C. leptum has been shown and particularly its major representative, Faecalibacterium prausnitzii. 12 Low doses of MTX can inhibit the function of several enzymes related to DNA synthesis, and downregulate a variety of inflammatory cytokines [such as interleukin (IL)-1, IL-2, IL-6, IL-8, etc.], thus inhibiting the proliferation of T lymphocytes and inflammatory response ( 52). A study has found that 72% of patients with active CD achieved clinical remission after 3 months of MTX treatment ( 53). A randomized controlled trial has shown that in patients with CD who have clinical remission after intramuscular treatment with 25 mg MTX per week, the rate of maintenance remission at 40 weeks of intramuscular treatment with 15 mg MTX per week is 65%, higher than that of the control group (39%, P = 0.04) ( 54). MTX has not been proven to have efficacy in inducing remission in UC ( 55). In addition, MTX can cause fatigue, nausea, vomiting, diarrhea, peritoneal abscess, hypoalbuminemia, atypical pneumonia, severe rash, etc. ( 27, 55). Calcineurin Inhibitors

Szczubelek et al, Effectiveness of Crohn’s disease exclusion diet for induction of remission in Crohn’s disease adult patients. Nutrients. 2021;12:4112. Finally, in addition to gut integrity, Modulen ® elements will likely benefit other organs and physiological processes allowing a well-being stage. Naturally, physical ameliorations go along with mental ones, thus achieving an effective quality of life.

Pharmacological Intervention

Among five patients who achieved remission at week 6, median FC level decreased from 630 (IQR 332–1586) μg/g to 230 (75–1298) μg/g (p=0.14). A 2019 randomized control study, first presented at ECCO, has helped to establish the general principles of the CDED. 23 Poate fi folosit ca sursă unică de nutriție în faza acută a bolii Crohn sau pentru completarea alimentației în perioadele de remisie; 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 Dietary management of CD has been documented, but we know that what works for CD does not necessarily work for UC. 27