Nutritional Therapy in Inflammatory Bowel Disease

Chen Sarbagili-Shabat; Rotem Sigall-Boneh; Arie Levine


Curr Opin Gastroenterol. 2015;31(4):303-308. 

In This Article

Dietary Interventions in Active Inflammatory Bowel Disease and Mechanisms of Response

Fiber has been touted as both harmful and beneficial in IBD, and restriction of fiber has been recommended in the past. A recent systemic review of clinical trials, involving 23 studies, found no effect for the supplementation of dietary fiber in 12 studies on Crohn's disease, a possible weak effect in ulcerative colitis in 3 of 10 studies, and a possible effect in pouchitis. Importantly, there was no evidence that fiber intake should be restricted in patients with IBD.[35] Another study that may have some ramifications for future studies involving dietary fiber and short-chain fatty acids as a dietary strategy was performed by the investigators from Melbourne, Australia. They randomized 25 patients with ulcerative colitis in remission or 12 healthy controls to one of two diets; low resistant starch, low wheat bran exposure or high resistant starch with high wheat bran over 2 weeks, then each group crossed over to the second diet after a washout period. In contrast to conventional wisdom, increased exposure to starch and fiber in the ulcerative colitis group did not increase short-chain fatty acid production and did not lead to a change in the composition of the microbiome. The authors concluded that individuals with ulcerative colitis have decreased ability to ferment nonstarch polysaccharides and starch.[36]

Exclusive enteral nutrition (EEN) is a well established method for inducing remission in children with recent-onset Crohn's disease.[37–39] Partial enteral nutrition (PEN) with free diet seems to be ineffective for the induction of remission.[40] A small retrospective German study found that the majority of children successfully completing a course of EEN will relapse during the first year and that 66% will respond to a second course of EEN with remission.[41] The mechanism whereby EEN induces remission has been controversial and two recent studies have shed light on the possible mechanisms. Previously postulated mechanisms of response have included an improvement on the effect of EEN on the microbiome, including an improvement in the diversity of the microbiome, improvement in protective species or increased butyrate production.[42] Scottish investigators evaluated 15 children before and after successful remission with EEN along with 21 controls. Contrary to the expectations, use of EEN was associated with a further decrease in diversity, decrease in specific 'protective species' and a decrease in butyrate in fecal samples.

A different line of thought was evaluated by the investigators from Israel.[43] They hypothesized that the major mechanism of effect is exclusion of dietary components hypothesized to cause dysbiosis or impair innate immune mechanisms such as the mucous layer, intestinal permeability or colonization and adherence with AIEC. They treated 47 patients with active Crohn's disease with PEN and a diet they coined as the Crohn's disease exclusion diet for 12 weeks. This is a structured diet with allowed and disallowed foods divided into two stages. Use of this diet led to clinical remission in 70% of patients by week 6. This was accompanied by a significant drop in C-reactive protein (CRP) and erythrocyte sedimentation rate through week 12, normalization of CRP in 70% of patients in remission and mucosal healing in a subset of responders. Importantly, 11 of 15 patients entering remission and practicing dietary restriction had mucosal healing. The results of this study done in humans suggest that specific dietary products play a role in inflammation. Use of PEN along with the Crohn's disease exclusion diet which contains whole foods such as lean chicken breast, fish, eggs, vegetables and rice offers the possibility of a more palatable and feasible diet and more widespread use of dietary therapy for the induction of remission in the future.

Although EEN has been widely accepted for the induction of remission, there has been a paucity of data regarding complete mucosal healing using rigorous criteria and prospective data collection. The Australian investigators prospectively evaluated clinical remission and mucosal healing using the Simple Endoscopic Score (SES) in 26 children receiving EEN for 8 weeks.[44] They confirmed that EEN is accompanied by mucosal healing, as 84% of patients entered clinical remission and 42% had complete mucosal healing. Importantly, 58% had complete or near-complete mucosal healing.

Multiple small studies have shown that PEN may be effective as a maintenance therapy to prevent clinical recurrence.[45–47] Yamamoto et al.[46] had previously shown that postoperative maintenance therapy with nightly tube feeding of an elemental formula with a low-fat diet can prevent endoscopic recurrence at 1 year. In a recent study, this same group extended their follow-up of the 40 patients in the original study to 5 years of follow-up.[47] Understandably, a decline in tube feeding was seen over time. At 5 years after resection, significantly more patients in the control group required biological therapy. A second resection was required in 5% of the PEN group and 25% of the control group (not significant). Postoperative recurrence is clearly an interesting avenue of research that has not been adequately evaluated to date. The Japanese investigators retrospectively evaluated the effect of PEN in addition to infliximab to reduce the loss of response to infliximab. Patients with normal CRP after the third induction of remission infusion were considered eligible. The authors divided their cohort of 102 patients into those who received at least 900 ml of an elemental formula in addition to infliximab (n = 45) and those who received no PEN or less than 900 ml/day (n = 57). Loss of response was defined as requirement for dose interval change or elevation of CRP greater than 1.5 mg/dl. At the end of follow-up, loss of response was significantly higher in the group treated solely with infliximab compared with the combination with an elemental formula.[48] These results contradict a previous prospective study that found no difference in the loss of response.[49] As this cohort was retrospective and the prospective study involved a fairly small study cohort, better studies are required before conclusions can be drawn.

There are very few studies that have evaluated successful dietary interventions in ulcerative colitis. Kyaw et al.[50] suggested that a dietary intervention based on the reduction in exposure to fat, simple carbohydrates, red meat and processed food can be beneficial in ulcerative colitis. They treated 61 ulcerative colitis adult patients over 4–6 weeks during a disease flare. By week 24, there was a modest but significant improvement in the activity score, suggesting that this may improve disease activity but could not induce remission.

Curcumin is a phenol compound that is the principal component of the spice turmeric.[51] Curcumin enemas were used for the induction of remission in mild-to-moderate distal colitis. Forty-five patients were randomized to either oral 5-aminosalicylic acid (5-ASA) with a curcumin enema or oral 5-ASA with a placebo enema. At week 8, clinical remission was observed in 43.4% of patients in the curcumin enema group compared with 22.7% in placebo group (not significant), and improvement on endoscopy in 52.2% of patients in active treatment group compared with 36.4% of patients in placebo group (not significant). As the authors did not show a significant difference and the study group was too small to reach significance, further studies are needed in order to evaluate the clinical significance of this type of therapy.

The relative success of dietary therapy for active Crohn's disease has led the investigators to evaluate the use of dietary therapies for other gut inflammatory conditions. Investigators from London evaluated the use of an elemental diet for chronic pouchitis.[52] Seven patients with pouchitis were treated with an exclusive elemental diet for 28 days. Use of EEN led to a significant decrease in stool frequency and the Pouch Disease Activity Index; however, there was no improvement in the endoscopic or histology scores.