Prebiotic Enriched Exclusive Enteral Nutrition Suppresses Colitis via Gut Microbiome Modulation and Expansion of Anti-inflammatory T Cells in a Mouse Model of Colitis

Exclusive enteral nutrition (EEN) is used to treat pediatric Crohn’s disease (CD), but therapeutic benefits are variable, and EEN can lead to microbial dysbiosis. Because of 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 hypothesized 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. TCR-β deficient (-/-) mice were randomized to 1 of 4 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 before experimental endpoint. Mice fed EEN IN showed greater colitis protection, with colonic shortening, goblet cell, and crypt density loss reduced compared with EEN fed mice and reduced disease activity and immune cell infiltration compared with chow fed mice, and less crypt hyperplasia and higher survival compared with both groups. EEN IN mice had less deterioration in the colonic mucus layer and had increased levels of Foxp3+IL-10+ and Rorγt+IL-22+ and reduced levels of Tbet+IFNγ+ and Tbet+TNF+ CD4+ T cells. EEN IN also led to higher butyrate concentrations, Bifidobacterium spp. and Anaerostipes caccae relative abundance, and lower [Clostridium] innocuum group spp. and Escherichia-Shigella spp. relative abundance. The EEN IN group showed reduced colitis development as compared with the chow and EEN groups. This highlights the potential benefits of EEN IN as a novel induction therapy for pediatric CD and UC patients. [Display omitted]