30June2020

Microbiome and diet: advances in the pathogenesis and treatment of Crohn’s Disease

Johan Van Limbergen, P-ECCO Member

Johan van Limbergen
© ECCO

Dietary advice in the management of IBD has evolved in recent years from having gastrointestinal symptom reduction as a goal to a more pathogenesis-focussed approach [1–4]. At present, dietary recommendations in adult Crohn’s Disease (CD) are limited to increasing dietary fibre by means of fruit and vegetables and decreasing processed foods [1]. The nutrition debate has long divided adult and paediatric CD care, from international guidelines all the way through to service provision arrangements, with growth failure being a common feature in paediatric CD and dietetic support being a mainstay of care in many children’s hospitals [5–7].  

With decades of clinical experience to build upon, recent guidelines in Europe and Canada have continued to position nutritional therapy [by means of exclusive enteral nutrition (EEN)] as a favoured induction option in paediatric CD, particularly considering the deleterious effects of corticosteroids on bone accrual, height velocity, lean body mass, mood and acne/cosmetic changes in young patients [van Rheenen et al. ECCO-ESPGHAN guidelines 2020, in press; 6, 8]. Recent paediatric trials have also shown the ability of EEN or controlled diet + partial EN to induce mucosal healing [9, 10].

It is becoming apparent that avoidance of the ‘regular’ diet is more important than the composition of the nutritional formula used for enteral nutrition [11, 12]. Several groups have shown that there is a quick rise in calprotectin after reintroduction of regular food, even though clinical remission is obtained prior to allowing a return to free diet [12, 13]. A more palatable and sustainable dietary intervention is necessary for increased use of nutritional therapy in adult care. Studies on the use of the Crohn’s Disease Exclusion Diet in adult CD that aim to confirm the improved tolerance and sustained remission seen in paediatric CD are eagerly awaited [13].

Sigall-Boneh et al. recently demonstrated that one can relatively quickly establish to what extent paediatric CD patients have a diet-responsive phenotype: after 3 weeks of good adherence to dietary therapy most patients who will achieve remission will have shown a convincing clinical response [14]. This provides a window of treatment optimisation, such as vaccination strategies in new patients. In established patients, dietary treatment has been shown to enable recapture of response to biologics [14–20]. Hisamatsu et al. reported the findings from the multicentre CERISIER trial, which studied patients with loss of response to standard dosing of infliximab (IFX): the trial was stopped prematurely after interim analysis due to clear superiority of combination therapy with partial enteral nutrition + IFX dose escalation over IFX escalation alone [21].

Combination of anti-inflammatory and nutritional therapy appears to be of particular benefit in the subgroup of patients who lose response to anti-inflammatory therapy, suggesting there is indeed a diet-responsive/microbiome-driven portion of the CD phenotype in addition to the inflammatory component addressed by means of anti-TNF or other biologics [15, 21]. This recent experience with nutritional therapy reaffirms the important role of the microbiome in CD pathogenesis. Previous studies of antibiotics had illustrated the clinical benefits of a tandem-approach (anti-inflammatory + microbiome regulation) in complicated patients [22, 23]. Future studies will be able to use these recent observations to reduce microbiome and diet heterogeneity among recruited patients, in order to assess the true benefit of anti-inflammatory treatment.

References

  1. Levine A, Rhodes JM, Lindsay JO, et al. Dietary guidance from the International Organization for the Study of Inflammatory Bowel Diseases. Clin Gastroenterol Hepatol. 2020;18:1381–92.
  2. Albenberg L, Brensinger CM, Wu Q, et al. A diet low in red and processed meat does not reduce rate of Crohn's disease flares. Gastroenterology. 2019;157:128–36.e5.
  3. Narula N, Dhillon A, Zhang D, et al. Enteral nutritional therapy for induction of remission in Crohn's disease. Cochrane Database of Syst Rev. 2018;4(4):CD000542.
  4. Miele E, Shamir R, Aloi M, et al. Nutrition in pediatric inflammatory bowel disease: a position paper on behalf of the Porto Inflammatory Bowel Disease Group of the European Society of Pediatric Gastroenterology, Hepatology and Nutrition. J Pediatr Gastroenterol Nutr. 2018;66:687–708.
  5. Sigall-Boneh R, Levine A, Lomer M, et al. Research gaps in diet and nutrition in inflammatory bowel disease. A topical review by D-ECCO Working Group [Dietitians of ECCO]. J Crohns Colitis. 2017;11:1407–19.
  6. Mack DR, Benchimol EI, Critch J, et al. Canadian Association of Gastroenterology clinical practice guideline for the medical management of pediatric luminal Crohn's disease. Gastroenterology. 2019;157:320–48.
  7. Krishnakumar C, Ballengee CR, Liu C, et al. Variation in care in the management of children with Crohn's disease: data from a multicenter inception cohort study. Inflamm Bowel Dis. 2019;25:1208–17.
  8. Ruemmele FM, Veres G, Kolho KL, et al. Consensus guidelines of ECCO/ESPGHAN on the medical management of pediatric Crohn's disease. J Crohns Colitis. 2014;8:1179–207.
  9. Urlep D, Benedik E, Brecelj J, et al. Partial enteral nutrition induces clinical and endoscopic remission in active pediatric Crohn's disease: results of a prospective cohort study. Eur J Pediatr. 2020;179:431–8.
  10. Pigneur B, Lepage P, Mondot S, et al. Mucosal healing and bacterial composition in response to enteral nutrition versus steroid based induction therapy – a randomized prospective clinical trial in children with Crohn's disease. J Crohns Colitis. 2019;13:846–55
  11. Logan M, Gkikas K, Svolos V, et al. Analysis of 61 exclusive enteral nutrition formulas used in the management of active Crohn's disease – new insights into dietary disease triggers. Aliment Pharmacol Ther. 2020;51:935–47.
  12. Logan M, Clark CM, Ijaz UZ, et al. The reduction of faecal calprotectin during exclusive enteral nutrition is lost rapidly after food re-introduction. Aliment Pharmacol Ther. 2019;50:664–74.
  13. Levine A, Wine E, Assa A, et al. Crohn's disease exclusion diet plus partial enteral nutrition induces sustained remission in a randomized controlled trial. Gastroenterology. 2019;157:440–50.e8.
  14. Sigall-Boneh R, Van Limbergen J, Wine E, et al. dietary therapies induce rapid response and remission in active paediatric Crohn’s disease. Clin Gastroenterol Hepatol. 2020 Apr 14;S1542-3565(20)30487-0. doi 10.1016/j.cgh.2020.04.006. Online ahead of print.
  15. Levine A, El-Matary W, Van Limbergen J. A case-based approach to new directions in dietary therapy of Crohn's disease: food for thought. Nutrients. 2020;12:880.
  16. Sigall-Boneh R, Sarbagili Shabat C, Yanai H, et al. Dietary therapy with the Crohn's Disease Exclusion Diet is a successful strategy for induction of remission in children and adults failing biological therapy. J Crohns Colitis. 2017;11:1205–12.
  17. Sood A, Singh A, Sudhakar R, et al. Exclusive enteral nutrition for induction of remission in anti-tumor necrosis factor refractory adult Crohn’s disease: the Indian experience. Intest Res. 2020;18:184–91.
  18. Hirai F, Takeda T, Takada Y, et al. Efficacy of enteral nutrition in patients with Crohn's disease on maintenance anti-TNF-alpha antibody therapy: a meta-analysis. J Gastroenterol. 2020;55:133–41.
  19. Hirai F, Ishihara H, Yada S, et al. Effectiveness of concomitant enteral nutrition therapy and infliximab for maintenance treatment of Crohn's disease in adults. Dig Dis Sci. 2013;58:1329–34.
  20. Nguyen DL, Palmer LB, Nguyen ET, et al. Specialized enteral nutrition therapy in Crohn's disease patients on maintenance infliximab therapy: a meta-analysis. Therap Adv Gastroenterol. 2015;8:168–75.
  21. Hisamatsu T, Kunisaki R, Nakamura S, et al. Effect of elemental diet combined with infliximab dose escalation in patients with Crohn's disease with loss of response to infliximab: CERISIER trial. Intest Res. 2018;16:494–8.
  22. Dewint P, Hansen BE, Verhey E, et al. Adalimumab combined with ciprofloxacin is superior to adalimumab monotherapy in perianal fistula closure in Crohn's disease: a randomised, double-blind, placebo controlled trial (ADAFI). Gut. 2014;63:292–9.
  23. Lamb CA, Kennedy NA, Raine T, et al. British Society of Gastroenterology consensus guidelines on the management of inflammatory bowel disease in adults. Gut. 2019;68:s1–s106.

Posted in ECCO News, Committee News, Congress News, Volume 15, Issue 2, P-ECCO

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