title: The human milk oligosaccharide 2'-fucosyllactose augments the adaptive response to extensive intestinal.
abstract: Intestinal resection resulting in short bowel syndrome (SBS) carries a heavy burden of long-term morbidity, mortality, and cost of care, which can be attenuated with strategies that improve intestinal adaptation. SBS infants fed human milk, compared with formula, have more rapid intestinal adaptation. We tested the hypothesis that the major noncaloric human milk oligosaccharide 2'-fucosyllactose (2'-FL) contributes to the adaptive response after intestinal resection. Using a previously described murine model of intestinal adaptation, we demonstrated increased weight gain from 21 to 56 days (P < 0.001) and crypt depth at 56 days (P < 0.0095) with 2'-FL supplementation after ileocecal resection. Furthermore, 2'-FL increased small bowel luminal content microbial alpha diversity following resection (P < 0.005) and stimulated a bloom in organisms of the genus Parabacteroides (log2-fold = 4.1, P = 0.035). Finally, transcriptional analysis of the intestine revealed enriched ontologies and pathways related to antimicrobial peptides, metabolism, and energy processing. We conclude that 2'-FL supplementation following ileocecal resection increases weight gain, energy availability through microbial community modulation, and histological changes consistent with improved adaptation.
authors.affiliation: Cincinnati Children's Hospital Medical Center, Division of Gastroenterology, Hepatology, and Nutrition; ethan.mezoff@cchmc.org.
authors.forename: Ethan A
authors.initials: EA
authors.lastname: Mezoff
authors.affiliation: Cincinnati Children's Hospital Medical Center, Division of Pediatric General and Thoracic Surgery;
authors.forename: Jennifer A
authors.initials: JA
authors.lastname: Hawkins
authors.affiliation: Cincinnati Children's Hospital Medical Center, Division of Biostatistics and Epidemiology;
authors.forename: Nicholas J
authors.initials: NJ
authors.lastname: Ollberding
authors.affiliation: Cincinnati Children's Hospital Medical Center, Division of Biomedical Informatics; and.
authors.forename: Rebekah
authors.initials: R
authors.lastname: Karns
authors.affiliation: Cincinnati Children's Hospital Medical Center, Division of Neonatology and Pulmonary Biology.
authors.forename: Ardythe L
authors.initials: AL
authors.lastname: Morrow
authors.affiliation: Cincinnati Children's Hospital Medical Center, Division of Pediatric General and Thoracic Surgery;
authors.forename: Michael A
authors.initials: MA
authors.lastname: Helmrath
mesh_terms: D000222:Adaptation, Physiological / Q000187:drug effects*; D000818:Animals; D002432:Cecum / Q000601:surgery; D004032:Diet; D013505:Digestive System Surgical Procedures; D004734:Energy Metabolism / Q000187:drug effects; D006801:Humans; D007082:Ileum / Q000601:surgery; D007422:Intestines / Q000187:drug effects* / Q000601:surgery*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D064307:Microbiota; D008895:Milk, Human / Q000737:chemistry*; D012336:RNA, Ribosomal, 16S / Q000096:biosynthesis; D012778:Short Bowel Syndrome / Q000188:drug therapy*; D014312:Trisaccharides / Q000737:chemistry / Q000494:pharmacology*; D015430:Weight Gain / Q000187:drug effects
chemical_list: D012336:RNA, Ribosomal, 16S; D014312:Trisaccharides; C031420:2'-fucosyllactose
keywords: 2′-fucosyllactose; human milk oligosaccharide; intestinal adaptation; short bowel syndrome