Crohn’s disease (CD) is a chronic inflammatory bowel condition often leading to complications requiring surgery. Optimizing nutrition before surgery contributes to reducing postoperative complications. The Crohn’s Disease Exclusion Diet (CDED), combined with Modulen as partial enteral nutrition (PEN), has been shown to help restore the intestinal barrier, promote a balanced immune response, and mitigate the inflammatory process (Modulen: Nestlé Italia S.p.A: Milan, Italy). Thus, this approach may be implemented into a prehabilitation protocol to tailor nutritional interventions for candidates undergoing CD surgery.
We describe four adult CD patients who underwent preoperative nutritional optimization with CDED+PEN. Interventions lasted 2–12 weeks, providing 30–35 kcal/kg/day, and were tailored based on weight and appetite. Adherence, nutritional markers, medical therapy, and surgical outcomes were monitored.
All patients showed good adherence and tolerance to CDED+PEN, with no flare-ups or treatment discontinuations. CDAI decreased in three of four cases. Nutritional status was maintained in all cases. CRP and albumin remained within normal values. Two patients discontinued biologics before surgery without complications, while two were managed without pharmacological therapy. All patients underwent robotic intestinal resection with no postoperative complications.
CDED+PEN may be incorporated into the prehabilitation protocol to enhance the nutritional and inflammatory status of CD patients undergoing surgery. Clinical trials assessing its efficacy and tolerance are warranted.
Crohn’s disease (CD) is a chronic, relapsing–remitting inflammatory bowel disease (IBD) characterized by transmural inflammation that can affect the entire intestine and particularly the distal ileum (
CD treatment is multidisciplinary, and its principal aims are to reduce active inflammation and to achieve and maintain clinical remission. Dietary therapy has been increasingly recognized as a key management strategy for CD, including the use of exclusive enteral nutrition (EEN) as a first-line therapy for pediatric CD, according to current guidelines (
The Crohn’s Disease Exclusion Diet (CDED) is a novel dietary therapy specifically designed for patients with CD to limit certain nutritional components, thereby reducing inflammation and achieving remission (
Nutritional support is also critical in the surgical setting. Poor nutritional status, including a body weight loss of more than 10% in the 6 months preceding surgery, has been associated with worse postoperative outcomes (
EEN is indicated in the preoperative period for patients with stenosing or fistulizing disease, aiming to improve nutritional status and reduce postoperative complications (
To date, evidence on CDED use in the preoperative setting is very scarce. To our knowledge, the only available clinical study was published by Wall et al. (
This perspective article describes the cases of four adult CD patients who received CDED + PEN in the preoperative period as part of a prehabilitation protocol aimed at improving patients’ fitness for surgery and postoperative outcomes. The enrolled patients were the first four consecutive patients observed. Our patients were initiated on and educated about the dietary treatment by a dietitian, who then assessed adherence and tolerability. The study is reported in accordance with the CAse REport (CARE) Guidelines and Checklist to ensure transparent and high-quality reporting (
Baseline clinical features.
| Clinical characteristics | Case 1 | Case 2 | Case 3 | Case 4 |
|---|---|---|---|---|
| Sex | F | F | F | M |
| Age at diagnosis | 43 | 31 | 29 | 30 |
| Age at surgery | 46 | 58 | 29 | 50 |
| Previous surgery | None | Yes | None | Yes |
| Therapy before surgery | Anti-TNF alfa Ustekinumab | Anti-TNF alfa Risankizumab | None | Azathioprine |
| Therapy at surgery | Anti-TNF alfa Ustekinumab | Risankizumab | None | None |
| Phenotype disease* | A3, L3-L4, B1 | A3, L3, B2 | A2, L3, B2 | A3, L3, B2 |
| Endoscopic activity (SES-CD) before surgery** | 16 | 16 | 15 | 14 |
*Phenotype disease: Montreal Classification. **Simple Endoscopic score for Crohn’s Disease (SES-CD).
We present a case of a 43-year-old Bangladeshi woman who presented for approximately 1 year with abdominal pain and diarrhea associated with low-grade fever and approximately 15% weight loss since symptom onset. Colonoscopy revealed pancolitis with serpiginous ulcers in the ileum (Simple Endoscopic Score for Crohn’s Disease - SES-CD 36). Esophagogastroduodenoscopy (EGDS) showed gastric antral ulcers and ulcers in the duodenal bulb (Montreal Classification A3, L3-L4, B1). A diagnosis of CD was made and confirmed by histological examination. The patient was initially treated with prednisone (50 mg/day for 4 weeks, then gradually tapered), and due to persistent endoscopic disease activity, infliximab was subsequently administered at 5 mg/kg every 8 weeks, later increased to 10 mg/kg every 4 weeks. After a prolonged period of clinical remission, the patient was compelled to reduce infliximab to 7.5 mg/kg at 4-week intervals due to the development of lesions consistent with a paradoxical psoriatic manifestation. After 5 months, an increase in inflammatory indices was observed: CRP levels increased to 10 times the normal value, and calprotectin levels reached 450 μg/g (normal value [n.v.] < 50 μg/g), without any other complications. Anti-IL12/23 therapy (ustekinumab) was therefore added to infliximab; however, no reduction in inflammatory indices was noted. During colonoscopy, an inflammatory stenosis of the ascending colon/ileocecal valve (SES-CD 16) was detected, without septic complications. The patient was referred to the surgical evaluation.
Four weeks before surgery, ongoing biological therapies (anti-TNF alpha and anti-IL 12/23) were suspended, and phase 1 CDED with PEN using Modulen was initiated, providing a total of 2,000 kcal/day (of which 1,000 kcal/day was from Modulen). Follow-ups every 2 weeks showed good adherence and tolerability to the diet. After 4 weeks, the Crohn’s Disease Activity Index (CDAI) decreased from 125 to 111, and no significant weight change was observed. Blood tests were within the normal range, except for a slight increase in CRP levels (
Summary of patient 1’s pre-surgical tests.
| Parameter | Baseline | Week 4 |
|---|---|---|
| CDAI | 124 | 111 |
| Body weight | 58 kg | 59 kg |
| BMI | 21.8 | 22.2 |
| BIA | Normal body composition | |
| Albumin | 3.9 g/dL | 4 g/dL |
| Pre-albumin | 26 mg/dL | 30 mg/dL |
| CRP | 50 mg/dL | 10 mg/dL (n.v. 5 mg/dL) |
| Fecal calprotectin | >1,000 μg/g | NA |
CDAI, Crohn’s Disease Activity Index; BIA, Body Impedance Assessment; BMI, body mass index; CRP, C-reactive protein; NA, not available.
We present the second case of a 58-year-old people of European descent woman who reported a recurrence of diarrhea lasting approximately 1 year, without blood or weight loss. She has had CD since the age of 31 years and was previously treated with emergency ileal resection surgery for an enterovesical fistula in 2001. Stool testing revealed high levels of fecal calprotectin (300 μg/g). Colonoscopy showed an inflammatory substenosis of the surgical anastomosis (Montreal Classification A3, L3, B2; SES-CD 12), confirmed by histological examination. Entero-MRI confirmed thickening of the perianastomotic ileal loop, showing mild dilation upstream of the anastomosis, with lengthening and approximation to the bladder. Anti-TNFα therapy was initiated with adalimumab 40 mg administered subcutaneously every 2 weeks and subsequently optimized to a weekly schedule. Following a temporary clinical benefit, the increase in calprotectin (350 μg/g) prompted a change in biological therapy to anti-IL-23 (risankizumab). After 6 months, colonoscopy revealed a tight stenosis of the surgical anastomosis (SES-CD 16). Entero-MRI confirmed the localization of the disease with a sub-stenosing fibrotic, characterized by thickening of the pre-anastomotic ileal tract extending approximately 6 cm, along with significant dilation of the upstream ileal tract. Following an episode of sub-occlusion, surgical resection of the stenotic tract was scheduled. A preoperative CT scan excluded the presence of abscess complications.
In anticipation of surgery, ongoing biological therapy was suspended, and phase 1 CDED with PEN using Modulen was initiated, providing a total of 2,000 kcal/day (of which 1,000 kcal/day was from Modulen). Follow-ups every 2 weeks showed good adherence and tolerability to the diet. After 6 weeks, the CDAI decreased from 119 to 106. Evaluated inflammatory markers were within the normal range (
Summary of patient 2’s pre-surgical tests.
| Parameter | Baseline | Week 6 |
|---|---|---|
| CDAI | 119 | 106 |
| Body weight | 62 kg | 62 kg |
| BMI | 23.3 | 23.3 |
| BIA | Normal body composition | NA |
| Albumin | 3.9 g/dL | 3.9 g/dL |
| Pre-albumin | 19 | 27 mg/dL |
| CRP | 6.4 mg/dL | Normal value |
| Fecal calprotectin | 233 μg/g | NA |
CDAI, Crohn’s Disease Activity Index; BIA, Body Impedance Assessment; BMI, body mass index; CRP, C-reactive protein; NA, not available.
We present the third case of a 29-year-old Tunisian woman woman with a known diagnosis of diagnosis of stenosing CD of the ascending colon presented to the emergency room with abdominal pain and diarrhea without blood. Colonoscopy revealed severe stenosis of the ascending colon (Montreal Classification A2, L3, B2; SES-CD 15), and histological examination confirmed the diagnosis of CD. Esophagogastroduodenoscopy was negative, and inflammatory markers remained unchanged. An entero-MRI confirmed a diffuse concentric thickening of the cecum and proximal ascending colon, with severe luminal reduction and stenosis over a 6-cm section involving the terminal ileum, with suspected entero-enteric fistulization and without abscess formation.
During the multidisciplinary discussion, surgical treatment was indicated, and phase 1 CDED with PEN using Modulen was initiated, providing a total of 2,000 kcal/day (of which 1,000 Kcal/day was from Modulen), pending surgical planning. A follow-up 2 weeks later showed good adherence and tolerability to the diet. The CDAI and body weight remained stable (
Summary of patient 3’s pre-surgical tests.
| Parameter | Baseline | Week 2 |
|---|---|---|
| CDAI | 131 | 131 |
| Body weight | 51 kg | 51 kg |
| BMI | 18.5 | 18.5 |
| BIA | Fat mass at the lower limits | NA |
| Albumin | 3.5 g/dL | 3.8 g/dL |
| Pre-albumin | 19 mg/dL | 20 mg/dL |
| CRP | 7.5 mg/dL | Normal value |
| Fecal calprotectin | NA | NA |
CDAI, Crohn’s Disease Activity Index; BIA, Body Impedance Assessment; BMI, body mass index; CRP, C-reactive protein; NA, not available.
We present a fourth case of a 50-year-old eople of European descent man diagnosed with CD following emergency ileocecal resection for perforation in 2004, and a subsequent colon resection extending to the transverse colon due to post-surgical complications. The patient had been treated for more than 10 years with low-dose cortisone and sub-therapeutic doses of azathioprine. The patient presented for reassessment of his disease. Abdominal ultrasound showed portal vein thrombosis and splenomegaly, along with thrombocytopenia (72,000/μL). EGDS revealed grade F2 esophageal varices, which were treated accordingly. Entero-MRI confirmed portal system thrombosis and stenosis of the surgical anastomosis, with dilation of the upstream segments and evidence of disease activity over a 30 cm section. Due to the critical presentation, the patient was started on EEN with Modulen (2,500 Kcal/day) and reported subjective improvement in wellbeing. After 4 weeks, the patient began the CDED diet (phase 1, totaling 1,500 kcal/day) with 1,000 kcal/day of Modulen. At the beginning of CDED, the patient had a CDAI of 110, a body weight of 86 kg, and excess fat mass with lean mass depletion, as evaluated by BIA. Follow-ups were conducted every 2 weeks. After approximately 8 weeks of the CDED protocol, colonoscopy revealed a tight stenosis of the ileum/transverse colon anastomosis, with no possibility to perform endoscopic dilatation (Montreal Classification A3, L3, B2, SES-CD 14). Therefore, after excluding hematologic and hepatologic causes underlying the portal vein thrombosis, the patient was deemed a candidate for surgery. During the CDED protocol, the patient reported some difficulty fully adhering to the dietary plan; however, CDAI and body weight remained essentially unchanged (weight loss: 0.05%). Albumin and inflammatory parameters were within normal limits (
Summary of patient 4’s pre-surgical tests.
| Parameter | Baseline (Day 0 CDED) | Week 2 | Week 8 |
|---|---|---|---|
| CDAI | 110 | 110 | 82 |
| Body weight | 86 | 86 | 82 |
| BMI | 25.5 | 25.5 | 24.7 |
| BIA | Excess fat mass, lean mass depletion | NA | NA |
| Albumin | NA | 3.7 g/dL | 3.6 g/dL |
| Pre-albumin | NA | 30 mg/dl | 35 mg/dL |
| CRP | 7 mg/dL | 5 mg/dl | |
| Fecal calprotectin | NA | NA | NA |
CDAI, Crohn’s Disease Activity Index; BIA, Body Impedance Assessment; BMI, body mass index; CRP, C-reactive protein; NA, not available.
The four patients underwent robotic intestinal resection surgery performed by the same surgical team using the daVinci surgical system Xi (Intuitive). The procedures and post-surgical outcomes in all cases are summarized in
Surgical procedure and post-surgical outcomes.
| Parameter | Case 1 | Case 2 | Case 3 | Case 4 |
|---|---|---|---|---|
| Surgical procedure | Single-stage lateral ileocecal resection (15 cm ileum) by minimally invasive surgery | Ileocolic resection of the previous single-stage anastomosis | Ileocolic resection with latero-lateral anastomosis by minimally invasive surgery | Resection of the ileocolic stenosis with the creation of a protective stoma due to the criticality of the abdominal picture linked to the presence of portal thrombosis |
| Complications | ||||
| Grade I–IV | None | None | None | None |
| Hospital length of stay (days) | 6 | 4 | 6 | 7 |
| Intra-operative stoma | No | No | No | Planned |
| Wound infection | No | No | No | No |
| Other infectious complications | No | No | No | No |
In CD management, surgery represents a significant therapeutic component, as more than half of CD patients undergo one or more surgical interventions during their lifetime (
The four described patients have heterogeneous characteristics; patients 1 and 2 were already on biological therapy and came to surgery due to complications of the disease despite medical treatment. Patient 3 came to surgery at diagnosis with subacute disease and was naïve to biological therapies. In contrast, patient 4 presented with a picture of stenosing CD in a previous surgical anastomosis, complicated by portal hypertension and previous immunosuppressive therapies. At baseline, none of them were diagnosed with malnutrition, defined as body mass index (BMI) < 18.5, according to the WHO definition.
Currently, the therapeutic value of nutritional support during the pre-surgical phase is controversial in patients without a condition of malnutrition. However, the feasibility study by Wall et al., although small in size, supports the rationale for evaluating effective preoperative nutritional optimization regimens to reduce the risk of postoperative complications, even in patients without obvious malnutrition (
In the described patients, the nutritional intervention lasted a minimum of 2 weeks and a maximum of 12 weeks, including 4 weeks of EEN and 8 weeks of CDED associated with PEN. Nutritional requirements were estimated at 30–35 kcal/kg/day and adjusted throughout the intervention period according to appetite and weight. Adherence to the dietary regimen, assessed by the dietitian every 2 weeks, also via telephone using targeted questions, was good in all patients. ESPEN recommends a minimum period of 7–14 days of nutritional intervention to have a positive impact on postoperative outcomes (
Regarding concomitant therapies, recommendations for suspending biological therapies before surgery have recently been updated. The 2024 ECCO Guidelines on Therapeutics in Crohn’s Disease: Surgical Management “recommend against cessation of biologics before surgery as the current evidence suggests that preoperative treatment with anti-TNF therapy, vedolizumab, and ustekinumab does not increase the risk of postoperative complications in CD patients undergoing abdominal surgery” (
These observations align with the existing evidence regarding the efficacy of CDED plus PEN in maintaining clinical remission and an adequate nutritional status. None of our patients underwent surgery for hypoalbuminemia. Hypoalbuminemia is common in patients with active CD and is associated with increased postoperative complications even in patients with normal BMI (
None of the patients experienced postoperative complications; however, it is worth emphasizing that the use of minimally invasive surgery may have contributed to a lower risk of complications (
In conclusion, the use of CDED+PEN in CD patients who are candidates for surgery was well tolerated and associated with good adherence. All patients demonstrated reasonable disease control without pharmacological therapy, and none experienced complications in the postoperative period. These observations support the implementation of CDED+PEN in the prehabilitation protocol, tailored explicitly for CD patients, even in the absence of evident malnutrition. Further studies are currently advocated to investigate the efficacy of CDED in optimizing surgical outcomes and preventing complications in CD patients undergoing surgery.
The original contributions presented in the study are included in the article/supplementary material, further inquiries can be directed to the corresponding author.
Written informed consent was obtained from the individual(s) for the publication of any potentially identifiable images or data included in this article. Written informed consent was obtained from the participant/patient(s) for the publication of this case report.
FV: Writing – original draft, Writing – review & editing. FG: Writing – original draft, Writing – review & editing. MC: Writing – original draft, Writing – review & editing. Nd’A: Writing – original draft, Writing – review & editing.
Editorial assistance was provided by Cristina Germanà, MD, and Maria Grazia Cassese on behalf of Menthalia Srl (Naples, Italy).
The author(s) declared that this work was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
The author(s) declared that Generative AI was not used in the creation of this manuscript.
Any alternative text (alt text) provided alongside figures in this article has been generated by Frontiers with the support of artificial intelligence and reasonable efforts have been made to ensure accuracy, including review by the authors wherever possible. If you identify any issues, please contact us.
All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.
Edited by:
Reviewed by: