An Inulin-Type Fructan Enriched Exclusive Enteral Nutrition Formula Suppresses Colitis Through Gut Microbiome Modulation and Promoting Expansion of Anti-Inflammatory T Cell Subsets

Abstract

Background & Aims: Exclusive enteral nutrition (EEN) is used to treat pediatric Crohns disease (CD), but therapeutic benefits are not long lasting. Due to reported lower efficacy EEN is not routinely used to treat pediatric ulcerative colitis (UC). Inulin-type fructans (IN) beneficially modulate the gut microbiome and promote expansion of anti-inflammatory immune cells. We hypothesised that enriching EEN with IN (EEN-IN) would enhance treatment efficacy. To test this, we examined the effects of EEN-IN on colitis development, the gut microbiome and CD4+ T cells using an adoptive T cell transfer model of colitis. Methods: TCR-beta deficient mice were randomised to one of four groups: 1) Control, 2) Chow, 3) EEN and 4) EEN-IN, and naive CD4+ T cells were adoptively transferred into groups 2-4, after which mice were monitored for 5-weeks prior to experimental endpoint. Results: Mice fed EEN-IN showed greater colitis protection, with colonic shortening, goblet cell and crypt density loss reduced over that of EEN fed mice and reduced disease activity and immune cell infiltration compared to chow fed mice, and less crypt hyperplasia and higher survival compared to both groups. EEN-IN mice maintained colonic mucus layer thickness and had increased levels of Foxp3+IL-10+ and Roryt+IL-22+ and reduced levels of Tbet+IFNy+ and Tbet+TNF+ CD4+ T cells. EEN-IN also lead to higher butyrate, Bifidobacterium spp. and Bacteroides spp. concentrations. Conclusion: The EEN-IN group showed reduced colitis development as compared to the chow and EEN groups. This highlights the potential benefits of EEN-IN as a novel induction therapy for pediatric CD and UC patients.