Abstract Background Dysbiosis of the gut microbiota is recognised as a major factor in the pathogenesis of inflammatory bowel disease (IBD). This study aimed to investigate the impact of gut microbiome changes induced by exclusive enteral nutrition (EEN) on the therapeutic course of biologic treatment in paediatric patients with Crohn’s disease. Methods The study prospectively recruited 48 paediatric patients newly diagnosed with moderate to severe Crohn’s disease. Clinical parameters and faecal samples for gut microbiome analysis were collected at five time points: at diagnosis (week 0), at the end of EEN treatment (week 8), one month after reintroduction of diet (week 12), following induction of infliximab (IFX), and at one year post-treatment. Results One-year time-course analyses of the gut microbiome revealed an EEN-induced perturbation followed by subsequent microbial recovery that approached healthy control profiles. Although all patients achieved clinical remission at the end of EEN treatment, those who initiated IFX at a later stage exhibited significantly greater microbial perturbation (lower gut microbiota diversity) at week 8 compared with those who started IFX within one month (p 0.05). Following EEN, the delayed IFX initiation group showed a significant decrease in Schaalia (p = 0.033). After IFX induction, patients who demonstrated better recovery of microbiome diversity did not experience loss of response and did not require dose intensification (p 0.001). Additionally, these high recoverers (from week 8 onwards) achieved biochemical and endoscopic remission after one year (p = 0.007 and p = 0.010, respectively). During longitudinal faecal assessments, Bilophila increased progressively in the group that failed to achieve one-year remission (p = 0.009). Conclusion Following EEN, a pronounced microbiome perturbation may allow deferral of biologic therapy, whereas rapid, pathobiont-sparing recovery of microbial diversity is associated with a reduced need for dose intensification and improved long-term outcomes. References: 1. Narula N, Dhillon A, Zhang D, Sherlock ME, Tondeur M, Zachos M. Enteral nutritional therapy for induction of remission in Crohn’s disease. Cochrane Database of Systematic Reviews. 2018;4(4):CD000542. doi:10.1002/14651858.CD000542.pub3 2. Swaminath A, Feathers A, Ananthakrishnan AN, Falzon L, Li Ferry S. Systematic review with meta-analysis: enteral nutrition therapy for the induction of remission in paediatric Crohn’s disease. Aliment Pharmacol Ther. 2017;46(7):645-656. doi:10.1111/apt.14253 3. Pigneur B, Lepage P, Mondot S, Schmitz J, Goulet O, Doré J, et al. Mucosal healing and bacterial composition in response to enteral nutrition vs steroid-based induction therapy: a randomized prospective clinical trial in children with Crohn’s disease. J Crohns Colitis. 2019;13(7):846-855. doi:10.1093/ecco-jcc/jjy207 4. Gerasimidis K, Bertz M, Hanske L, Junick J, Biskou O, Aguilera M, et al. Decline in presumptively protective gut bacterial species and metabolites are paradoxically associated with disease improvement in pediatric Crohn’s disease during enteral nutrition. Inflamm Bowel Dis. 2014;20(5):861-871. doi:10.1097/MIB.0000000000000023 Conflict of interest: Prof. Kwon, Yiyoung: No conflict of interest Kim, Yoon Zi: No conflict of interest Jeong, Tae Jong: No conflict of interest Choe, Yon Ho: No conflict of interest Kim, Mi Jin: No conflict of interest
Kwon et al. (Thu,) studied this question.