title: Advancing nutritional therapy: A novel polymeric formulation attenuates intestinal inflammation in a murine colitis model and suppresses pro-inflammatory cytokine production in ex-vivo cultured inflamed colonic biopsies.
abstract: Nutritional therapy is a viable therapeutic option for the treatment of Crohn disease (CD). Therefore improving nutritional therapy would greatly benefit CD patients. The aim of this study was to define the anti-inflammatory properties of a novel nutritional polymeric formula (PF) in comparison to a currently available standard PF.
  
  
  
  Dextran sodium sulfate (DSS) was utilized to induce colitis in C57BL/6 mice with mice randomized to receive either standard PF or novel PF in addition to control groups. Changes in body weight were recorded and colonic damage was assessed histologically and biochemically. Additional experiments were also included where the cytokine response of colonic biopsies from pediatric CD patients was measured following exposure to standard PF or novel PF.
  
  
  
  DSS induced significant body weight loss, morphological changes in the colon, increased myeloperoxidase (MPO) activity and up-regulated colonic mRNA expression of tumor necrosis factor (TNF)-α, interleukin (IL)-6, IL-12 and monocyte chemoattractant protein (MCP)-1, as well as associated histological changes. Other than histological damage, these inflammatory changes were reversed by both novel and standard PF. However, the novel PF, but not standard PF, completely suppressed TNF-α, IL-6 and IL-8 levels from cultured biopsies.
  
  
  
  Newly developed nutritional formula reproducibly ameliorated DSS-induced colitis in a murine model, although this response was not measurably different to standard PF. However, the novel PF was significantly superior in suppressing inflammatory cytokine release from cultured colonic biopsies. Collectively, these findings support a possible role for novel PF in advancing nutritional therapy for CD patients.
authors.affiliation: Discipline of Paediatrics, School of Women's and Children's Health, Medicine, University of New South Wales Sydney, NSW, Australia.
authors.forename: Moftah H
authors.initials: MH
authors.lastname: Alhagamhmad
authors.affiliation: Discipline of Paediatrics, School of Women's and Children's Health, Medicine, University of New South Wales Sydney, NSW, Australia; Department of Gastroenterology, Sydney Children's Hospital, Randwick, NSW, Australia.
authors.forename: Daniel A
authors.initials: DA
authors.lastname: Lemberg
authors.affiliation: Discipline of Paediatrics, School of Women's and Children's Health, Medicine, University of New South Wales Sydney, NSW, Australia; Paediatrics, University of Otago, Christchurch, New Zealand.
authors.forename: Andrew S
authors.initials: AS
authors.lastname: Day
authors.affiliation: Department of Gastroenterology, Sydney Children's Hospital, Randwick, NSW, Australia.
authors.forename: Li-Zsa
authors.initials: LZ
authors.lastname: Tan
authors.affiliation: Discipline of Paediatrics, School of Women's and Children's Health, Medicine, University of New South Wales Sydney, NSW, Australia; Department of Gastroenterology, Sydney Children's Hospital, Randwick, NSW, Australia.
authors.forename: Chee Y
authors.initials: CY
authors.lastname: Ooi
authors.affiliation: Discipline of Paediatrics, School of Women's and Children's Health, Medicine, University of New South Wales Sydney, NSW, Australia; Department of Gastroenterology, Sydney Children's Hospital, Randwick, NSW, Australia.
authors.forename: Usha
authors.initials: U
authors.lastname: Krishnan
authors.affiliation: Department of Gastroenterology, Sydney Children's Hospital, Randwick, NSW, Australia.
authors.forename: Nitin
authors.initials: N
authors.lastname: Gupta
authors.affiliation: Department of Pathology, Institute of Veterinary, Animal and Biomedical Sciences, Massey University, Palmerston North 4442, New Zealand.
authors.forename: John S
authors.initials: JS
authors.lastname: Munday
authors.affiliation: Discipline of Paediatrics, School of Women's and Children's Health, Medicine, University of New South Wales Sydney, NSW, Australia. Electronic address: s.leach@unsw.edu.au.
authors.forename: Steven T
authors.initials: ST
authors.lastname: Leach
mesh_terms: D000293:Adolescent; D000305:Adrenal Cortex Hormones / Q000627:therapeutic use; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000627:therapeutic use; D001706:Biopsy; D002648:Child; D002675:Child, Preschool; D003092:Colitis / Q000139:chemically induced / Q000178:diet therapy*; D003106:Colon / Q000378:metabolism*; D003424:Crohn Disease / Q000178:diet therapy; D016207:Cytokines / Q000235:genetics / Q000378:metabolism*; D016264:Dextran Sulfate / Q000633:toxicity; D004195:Disease Models, Animal; D005260:Female; D006801:Humans; D007249:Inflammation / Q000139:chemically induced / Q000178:diet therapy*; D051379:Mice; D008810:Mice, Inbred C57BL; D046509:Tissue Culture Techniques
chemical_list: D000305:Adrenal Cortex Hormones; D000893:Anti-Inflammatory Agents; D016207:Cytokines; D016264:Dextran Sulfate
keywords: Crohn disease; Ex-vivo model; Experimental colitis; Nutritional therapy