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

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

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