P1327 Crohn disease exclusion diet maintenance therapy induces sustained microbiomes changes

Abstract Background Crohn disease (CD) exclusion diet plus partial enteral nutrition (CDED+PEN) and exclusive enteral nutrition (EEN) are both effective at inducing remission in paediatric CD. The objectives of the current study were to characterize temporal microbiome alterations in children with CD receiving either CDED+PEN or EEN, and determine if microbiome restoration (more closely resembling healthy controls) was associated with sustained remission. We hypothesized that the diet therapies would induce distinct changes to the gut microbiome, and that this would be linked to improved clinical outcomes. Methods In a multi-centre randomized controlled trial, children (12.7 ± 2.4 years) with mild-to-severe CD received EEN for 2 weeks followed by CDED+PEN (n = 30) for up to 24 weeks, or 8 weeks of EEN followed by PEN with free diet (n = 26). Fecal samples were collected at baseline and weeks 2, 8, 14, and 24 from patients, and at baseline from healthy family members (FM; n = 108). Samples were subjected to 16S rRNA gene amplicon sequencing, and linear mixed models were applied; false discovery rate-adjusted p < 0.05 was considered significant. Results At baseline, patients with CD had microbiome signatures distinct from healthy FM, with 26 differentially abundant bacterial genera (all p < 0.05). Two weeks of EEN induced microbiome compositional changes in both diet groups, such as reducing fibre-degrading taxa (e.g., Bifidobacteria, Faecalibacterium; p < 0.01), effects which were maintained in the EEN group by week 8. CDED+PEN increased relative abundances of Ruminococcus (p = 0.006), Lachnospiraceae_NK4A136_group (p = 0.008), and Monoglobus (p = 0.023) at week 8 compared to EEN. However, only CDED+PEN maintained certain taxonomic changes at weeks 14 and 24 (e.g., increased uncultured Oscillospiraceae, Christensenellaceae R-7 group), suggesting sustained diet-induced alterations to the microbiome. CDED+PEN further reduced Oscillospiraceae UCG-005 at weeks 8 and 14 compared to healthy FM, and only patients in sustained remission at week 24 maintained lower Oscillospiraceae UCG-005 abundance compared to FM. Conclusion CDED+PEN induced gut microbiota compositional alterations distinct to EEN. Despite gradual liberation of diet in the CDED+PEN group, certain gut microbiota changes were sustained in the long-term. Diet-induced microbiome alterations were linked to sustained long-term remission, potentially serving as biomarkers of positive clinical outcomes in pediatric CD. Our findings may help establish a framework for personalizing diet therapies based on the gut microbiome to optimize outcomes for pediatric patients with CD. Conflict of interest: Dr. Armet, Anissa: Personal fees from Nestlé for travel to conferences. Sigall-Boneh, Rotem: Personal Fees: Speaker fees- Nestlé Health Science, Takeda and Megapharm, Janssen Consulting- Nestlé Health Science Advisory board- Evinature Writing -Tnuva Zhao, Yanyan: None. Luo, Lingxuan: None. Navas López, Víctor Manuel: In the last 5 years, I have received compensation for consulting work, research grants, or fees for scientific activities from the following companies: Abbvie, Otsuka, Adacyte, Nestlé Health Science, Abbott, Mead&Johnson-Rb, Lactalis, Nutricia, Casen Recordati, Hero, Grifols, and Ordesa. Hussey, Séamus: Grant: I have received unrelated research grants from Janssen in the past 3 years Pujol Muncunill, Gemma: Honoraria and personal fees from Nestle Health Science, Adacyte, Pfizer, Abbvie, Janssen, Nutricia. Lawrence, Sally: None. Jonsson Rolandsdotter, Helena: None. Otley, Anthony: I have an investigator initiated research grant from AbbVie Global. I am site PI for clinical trials with Pfizer, AbbVie, Eli Lilly and Janssen. Martin de Carpi, Francisco Javier: Grant: Otsuka, Nestle Other: Abbvie, Nestle, Kern, Celgene, Lilly, Celtrion, Roche Li, Fuyong: None. Van Limbergen, Johan: Grant: Nestle Health Sciences, Janssen Personal Fees: Abbvie, Nestle Health Sciences, Janssen, Pfizer Non-financial Support: Nestle Health Sciences Other: Novalac Wine, Eytan: Personal Fees: Janssen, AbbVie, Nestle Health Sciences, Mead Johnson Nutrition, Pfizer, BioJamp