EEN in Pre-Operative Optimisation in Crohn’s Disease: History
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Contributor:
Rachel Cooney
,
,
Gordon W. Moran

Crohn’s disease (CD) is a chronic inflammatory disease of the gastrointestinal tract, with increasing incidence worldwide. Exclusive enteral nutrition is the term used when a patient replaces their habitual diet with an exclusive liquid diet for a defined period. In clinical practice, the most frequent form of exclusive enteral nutrition (EEN) used is polymeric liquid feeds, for example, Fortisip™, Ensure™, or Modulen™. EEN is used extensively in the paediatric population to induce remission, but is not routinely used in the induction of remission of adult Crohn’s disease or in pre-operative optimisation.

  • Crohn’s disease
  • exclusive elemental nutrition
  • pre-operative

1. Introduction

Crohn’s disease (CD) is a chronic inflammatory disease of the gastrointestinal tract, with increasing incidence worldwide [1][2]. Although incidence is stabilising in western countries, prevalence continues to rise. In the U.K., it is predicted that the prevalence of inflammatory bowel disease (IBD) will be 1% by 2030 [3][4][5].
Medications such as oral immunosuppressants and biologics are the mainstay of the treatment of CD [6]. However, surgery continues to have a role in disease management. The main indications for surgery are stricturing disease, penetrating complications, and medication-refractory inflammatory disease [7].
The European Crohn’s and Colitis Organisation (ECCO) and the European Society of Coloproctology (ESCP) consensus guidelines suggest surgery should be considered at an early stage for those with penetrating or fistulising disease and those with localised ileocaecal disease and obstructive symptoms but no significant active inflammation [8]. The objective of surgery is to provide symptomatic relief and preserve as much bowel function as possible. There is a suggestion that the current, more aggressive, treat-to-target approach reduces surgical rates [9][10][11][12]. Despite these recent decreases, 23–47% of patients still require surgery at some stage in their disease course [13][14][15]. Within 5 years of diagnosis, approximately 25% of patients require surgery, with rates being the highest amongst those with ileocolonic disease. Disease recurrence is common at or close to the anastomotic site, with most patients developing new endoscopic lesions within one year of surgery, and 17–33% of patients will need a second resection in the 10-year period following the first [16].
Surgery may be the preferred first-line treatment for isolated ileocaecal CD, as shown by the Lir!c study, which demonstrated that primary resection in patients with isolated ileocecal disease had similar quality of life scores one year after surgery as compared to medical treatment [17].
Exclusive enteral nutrition is the term used when a patient replaces their habitual diet with an exclusive liquid diet for a defined period [18][19]. In clinical practice, the most frequent form of exclusive enteral nutrition (EEN) used is polymeric liquid feeds, for example, Fortisip™, Ensure™, or Modulen™. Polymeric feeds are more palatable, and there is no difference in outcomes between elemental and polymeric feeds (see below).
The 2020 ECCO review of peri-operative dietary therapy in IBD recognises that EEN shows promise as a pre-operative optimisation strategy for reducing complications and improving nutritional status and acknowledges a pressing need for large prospective studies to inform clinical practice [20].
The aim of EEN in CD in the pre-operative setting is to:
(1) Improve nutritional status and thus reduce surgical complications and enhance post-operative recovery [21][22].
(2) Reduce Crohn’s-related inflammation, thus reducing pre-operative steroid use and optimising the patient for surgery.

2. Timing of Surgery in Crohn’s Disease

Steroid dependency can occur in patients with a longstanding diagnosis of Crohn’s disease [23][24]. The most feared post-operative complications in Crohn’s disease surgery are intra-abdominal septic complications, such as anastomotic leakage, intra-abdominal abscess, and enteral fistulae [25]. Most of these patients will need drainage or reoperation and may require stoma formation [7][26][27].
There is a window of optimal timing for surgery in Crohn’s disease, i.e., the sweet spot. Ideally, the patient is in remission, off steroids, and well-nourished. It has been argued that the timing of Crohn’s disease surgery can be even more vital than the timing of cancer surgery; operate too soon, when the patient is on steroids, just post anti-TNF treatment, and malnourished, the risk of post-operative complications will be high. Defer surgery too long, and the patient flares again, needs steroids again, and becomes malnourished; hence, the risks rise again.
The role of the multidisciplinary team (MDT) is key in achieving optimal timing for surgery.
Other key factors in pre-operative optimisation should not be overlooked, particularly the treatment of any sepsis with radiological intervention and antibiotic therapy, and attention to venous thromboembolism risk management. In addition, this time can be used to implement smoking cessation measures. See Table 1.
Table 1. Key risk factors for complications.

Risk Factor

Evidence for Role of EEN—References

Steroid dependency [28]

Yes [29][30][31]

Active disease [32]

Yes [30]

Sepsis [28]

Drain if possible.

EEN may assist in management alongside antibiotics [30][33][34]

Impaired nutritional status [32]

May help

3. Could EEN Reduce the Risk of Post-Operative Crohn’s Disease Recurrence?

The microbiome supports intestinal homeostasis and the immune function, and it is widely accepted that disruptions in host–microbiome interactions are the driving force behind tissue-damaging inflammation in CD [35]. Although the exact mechanism of action of EEN is not known, the current hypothesis suggests it works through the exclusion of dietary components that interact with inflammatory components of the gut microbiome [36][37].
Many research studies found that compared to CD patients, healthy subjects had high biodiversity, dominated by Firmicutes, Bacteroidetes, and Proteobacteria phyla [38]. Biodiversity is lower in CD patients at the time of surgery, but is increased after surgery, whilst still different from healthy subjects [39]. Bacterial dysbiosis and a low abundance of Faecalibacterium prausnitzii, in both resected and post-operative ileal mucosa, have been associated with an increased risk of endoscopic recurrence [40][41][42]. One study looked at the post-operative Crohn’s recurrence rates after at least 4 weeks of EEN [43]. At 6 months after laparoscopic surgery, the rate of endoscopic recurrence was significantly lower in the EEN group ((11.9% vs. 28.4%, p = 0.044). At 12 months, the difference, however, was not significant (26.2% vs. 37.3%, p = 0.059). The rates of clinical recurrence at 12 months were four (8.9%) patients in the EEN group and nine (12.0%) patients in the non-EEN group (p = 0.820) [43]. Potentially, the continuation of EEN or PEN post-operatively could result in lower long-term recurrence rates. Cohort studies found that nocturnal EN in the post-operative period may reduce clinical and endoscopic recurrence among adult patients with CD [44][45]. Assessing the changes in the microbiome during EEN could reveal which microbes and microbial metabolites play a role in the aetiology of CD.

4. EEN Use in Practice

Interest in therapeutic diets has grown in recent years, and questions regarding diet are common in IBD clinical care. Dietary advice is part of the personalised care plans advocated by national bodies [6].
EEN is not routinely used to induce or maintain remission in adult populations. Anecdotally, some centres use EEN pre-operatively in selected patients, namely those who are malnourished and at high risk of surgical complications, to improve nutrition, wean them off steroids, and even allow a period of smoking cessation prior to operation. It may be that in adults, EEN is most effective in this setting. Routine use has not been adopted due to a combination of factors, including the lack of robust prospective studies, perceived compliance issues, patient preference, and limited access to dietetic expertise within an IBD multidisciplinary team [46].
Patients may be more willing to comply with EEN if this could reduce the risk of post-operative complications, including stoma formation, and allow a shorter hospital stay and a faster return to work. Stoma formation is something many patients are keen to avoid, and this may be a factor in patient compliance [47][48].
To help address this, an Australia and New Zealand working group developed a care pathway for EEN use in adults with CD [49].
Many questions arise when considering EEN. A common question is whether all daily calorie intake must be from formula feeds. Recent studies showed partial enteral nutrition together with a specific CD exclusion diet can induce remission in children and adults [50][51][52]. This may help compliance, but there are currently no studies of this in the post-operative setting.
Many of the studies in China used an NG tube to deliver feed, but the efficacy of EEN in CD is independent of the route of administration, and in the researchers' experience, patients most commonly opt for oral rather than the NG route [53].
The type of formula feed used varies across studies, but if we extrapolate from the paediatric population, one formula is not superior to another [54]. This means that an adult patient who does not tolerate one form of formula feed can be offered an alternative until a feed is found that the patient can tolerate. Of note, in the study by Gordon-Dixon et al., Modulen™ IBD was used as first-line treatment, but if this was not tolerated, Ensure™ was offered, with a liquid diet as third-line treatment. Of the 24 patients in this study, 17 tolerated Modulen™, 5 Ensure™, and 2 a standard liquidised diet.

This entry is adapted from the peer-reviewed paper 10.3390/nu13124389

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