P1330 Fiber Intake and Diet Health Index of Recipients as Modulators of FMT Response in UC: A Post Hoc Analysis

Abstract Background Rigorous donor preselection, strict anaerobic processing, and repeated faecal microbiota transplantation (FMT) administration did not improve outcomes for induction of clinical remission in the RESTORE-UC trial1. To better understand these results and inform future FMT trial designs, we investigated dietary patterns and fiber intake of recipients, and their associations with microbial composition, and ecosystem shift from dysbiosis. Methods The RESTORE-UC trial was a multi-centric double-blind, sham-controlled randomized trial. Patients with moderate to severe UC (total Mayo 4–10) were randomly allocated to receive four anaerobic-prepared allogenic or autologous donor FMTs. Food Frequency Questionnaires (FFQs) were collected at weeks 0 (n = 62) and 8 (n = 52) from recipients. From these, a population-specific diet health index was derived taking into account diet quality, equilibrium and diversity2. Subsequently, k-means clustering was performed on daily intake of whole food groups. Quantitative microbiota profiling (QMP) was conducted on patient stool samples collected at weeks 0 (n = 44) and 8 (n = 44). We correlated dietary clusters and diet health scores with microbial genus abundances during induction phase (week 0 - 8). Clinical success was evaluated at week 8, including steroid-free clinical remission as well as clinical/endoscopic response (≥3 or ≥ 50% reduction in combined Mayo subscores for rectal bleeding and stool frequency). Microbiota success was defined as enterotype shift with restoration of eubiosis (Bacteroides 2 (B2) to non-B2 enterotype), and other subtypes including no transition, non-B2 to other non-B2 transition, lead dysbiosis (non-B2 to B2), and maintenance of dysbiosis (B2 to B2). Results At week 8, patients restoring eubiosis showed a weak trend towards a higher percentage Dietary Health Index (%DHI) (Kruskal-Wallis; p = 0. 07; Fig. 1A) and greater fiber intake per 1000 kcal (p = 0. 14). Yet, no association with clinical success was found. K-mean clustering identified two main dietary patterns (Fig 1B). Key whole food contributors to cluster separation include coffee with both sweeteners and sugar addition, alcoholic beverages, (all adj. p 0. 05), vegetables (p 0. 01; adj. p = 0. 06) and brown bread (p = 0. 03; adj. p = 0. 15) (Fig 1C). Linear regression revealed modest associations between FFQ-derived intake and QMP genera, with effect sizes varying across both metadata and whole food variables (Fig 1D-E). Conclusion This post-hoc analysis of the RESTORE-UC trial suggests that dietary improvements - particularly higher fiber intake - may enhance microbial restoration post-FMT. A lack of statistical power due to the limited number of clinical and microbial responders underscores the need for further investigation. References: 1. Caenepeel, C. et al. RIGOROUS DONOR SELECTION FOR FMT IN ACTIVE ULCERATIVE COLITIS: KEY LESSONS FROM A RANDOMIZED CONTROLLED TRIAL HALTED FOR FUTILITY. Clinical Gastroenterology and Hepatologyhttps: //doi. org/10. 1016/j. cgh. 2024. 05. 017 (2024) doi: 10. 1016/j. cgh. 2024. 05. 017. 2. Huybrechts, I. et al. Reproducibility and validity of a diet quality index for children assessed using a FFQ. British Journal of Nutrition 104, 135–144 (2010). Conflict of interest: Ms. Deleu, Sara: Grant: Sara Deleu has received the ECCO fellowship in 2024 and is currently an FWO junior postdoctoral fellow (1255426N). Other: Sara Deleu has been listed as a co-inventor on an international patent application entitled ‘Improved probiotic potency of the yeast Saccharomyces boulardii’ PCT/EP2023/051941. Vazquez Castellanos, Jorge Francisco: No conflict of interest Derrien, Muriel: No conflict of interest Caenepeel, Clara: No conflict of interest Vissers, Eva: No conflict of interest Arnauts, Kaline: No conflict of interest Verstockt, Sare: No conflict of interest Proost, Sebastian: SP is listed as the inventor on PCT/EP2021/077386 (WO2022073973A1) covering methods to diagnose and treat or reduce the severity of gut flora dysbiosis as well as of gastro-intestinal inflammation and inflammation-associated disorders or conditions in a subject in need thereof and on patent application PCT/EP2024/086588 (WO2025125682) describing means and methods to classify the gut microbiome. Baert, Filip J.: Grant: AbbVie, Amgen, EG, J&J, Takeda. Personal Fees: AbbVie, Abivax, Alpha Sigma, Arena, BMS, Celltrion, Eli Lilly, Falk, Ferring, Fresenius, Galapagos, J&J, Pfizer, Sandoz, Takeda, Vifor. Mana, Fazia: No conflict of interest Pouillon, Lieven: Lieven Pouillon received advisory board fees from AbbVie, Alphasigma, Celltrion, Galápagos, Janssen-Cilag, Sandoz and Takeda consultancy fees from Ipsos NV and Ismar Healthcare funded by Viatris presentation fees from AbbVie, Alphasigma, Celltrion, Eli Lilly, Ferring, Galápagos and Pfizer and personal fees (congress support) from AbbVie, EG, Ferring, Galápagos, Janssen-Cilag, Norgine and Takeda. Lobatón Ortega, Triana: Grant: Abbvie, Ferring, Viatris, MSD, EG, Mundipharma, Biogen, Janssen, Pfizer, Takeda, Galapagos, Afasigma and Sandoz. Personal Fees: Speaker fees from MSD, Abbvie, Janssen, Amgen, Fresenius Kabi, Galapagos, Viatris, Ferring, Celltrion, Alfasigma, Lilly and Takeda. Consultancy fee from Janssen, Galapagos, Alfasigma, Amgen, Bristol Myers, Squibb Fresenius Kabi, Takeda and Abbvie Louis, Edouard: Education and Reserach Grants for my department: Abbvie, Takeda, Johnson and Johnson, Pfizer, Fresenius-Kabi, Celltrion, EG pharma, Sandoz, Falk Personal Fees for conferences, advisory boards and consultancy: Abbvie, Takeda, Ferring, Pfizer, Johnson and Johnson, Lilly, Galapagos, Celltrion, Arena, BMS, Falk, Biokuris, Fresenius-Kabi, Thabor Franchimont, Denis: Research grants from: Abbvie, Takeda, Janssen, Celltrion, Amgen, MSD, Cantocor, EG, Eli Lilly, and Alfa sigma Consultancy & Speakers’ fees from: Abbvie, Takeda, Janssen, Pfizer, Amgen, MSD, Centocor, Galapagos, GILEAD, Ferring, Falk, Chiesi, Mundipharma, Hospira and Celltrion. Verstockt, Bram: - support from AbbVie, Biora Therapeutics, Celltrion, Landos, Pfizer, Sanofi, Sossei Heptares/Nxera and Takeda. -’s fees from Abbvie, Agomab, Alfasigma, Biogen, Bristol Myers Squibb, Celltrion, Eli Lily, Falk, Ferring, Galapagos, Materia Prima, Johnson and Johnson, Pfizer, Sandoz, Takeda, Tillots Pharma, Truvion and Viatris. - fees from Abbvie, Alfasigma, Alimentiv, Anaptys Bio, Applied Strategic, Astrazeneca, Atheneum, BenevolentAI, Biora Therapeutics, Boxer Capital, Bristol Myers Squibb, Domain Therapeutics, Eli Lily, Galapagos, Guidepont, Landos, Merck, Mirador Therapeutics, Mylan, Nxera, Inotrem, Ipsos, Johnson and Johnson, Pfizer, Sandoz, Sanofi, Santa Ana Bio, Sapphire Therapeutics, Sosei Heptares, Takeda, Tillots Pharma and Viatris. - options Vagustim and Thethis Pharma. Ferrante, Marc: Research grants from AbbVie, EG Pharma, Celltrion, Janssen, Pfizer, Takeda and Viatris Consultancy fees from AbbVie, AgomAb Therapeutics, Boehringer Ingelheim, Celgene, Celltrion, Eli Lilly, Janssen-Cilag, MRM Health, Merck Sharp and Dohme, Pfizer, Takeda and ThermoFisher Speakers’ fees from AbbVie, Biogen, Boehringer Ingelheim, Dr Falk Pharma, Ferring, Janssen-Cilag, Merck Sharp and Dohme, Pfizer, Takeda, Truvion Healthcare and Viatris Vermeire, Séverine: Grant: AbbVie, Pfizer, Takeda, J&J, Galapagos Personal Fees: AbbVie - AbolerIS Pharma - AgomAb - Alimentiv - Arena Pharmaceuticals - AstraZeneca - Avaxia- BMS - Boehringer Ingelheim - Celgene - CVasThera - Dr Falk Pharma - Ferring - Galapagos - Genentech-Roche - Gilead - GSK - Hospira - Imidomics - Janssen - J&J - Lilly - Materia Prima - MiroBio - Morphic - MrMHealth - Mundipharma - MSD - Pfizer - Prodigest - Progenity - Promakhos Therapeutics - Prometheus - Robarts Clinical Trials - Second Genome - Shire - Surrozen - Takeda - Theravance - Tillots Pharma AG - Zealand Pharma - Other: AbbVie, MSD, Takeda, Ferring, Genentech/Roche, Shire, Pfizer Inc, Galapagos, Mundipharma, Raes, Jeroen: JR has received grants from Beneo, Cargill, Colruyt group, Danone, DSM, J&J, MRM/Prodigest, Nestle, Pfizer, Takeda and VectivBio and has received consulting and/or speaking fees from Aphea, Biofortis, DSM-Firmenich, Ferring, GSK, Janssen Pharmaceuticals, Metagenics, MSD, MRM/Prodigest, Nutricia, Takeda, Tsumura JR listed as the inventor on PCT/