title: Branched chain fatty acids reduce the incidence of necrotizing enterocolitis and alter gastrointestinal microbial ecology in a neonatal rat model.
abstract: BACKGROUND
  Branched chain fatty acids (BCFA) are found in the normal term human newborn's gut, deposited as major components of vernix caseosa ingested during late fetal life. We tested the hypothesis that premature infants' lack of exposure to gastrointestinal (GI) BCFA is associated with their microbiota and risk for necrotizing enterocolitis (NEC) using a neonatal rat model.
  
  
  METHODS
  Pups were collected one day before scheduled birth. The pups were exposed to asphyxia and cold stress to induce NEC. Pups were assigned to one of three experimental treatments. DF (dam-fed); Control, hand-fed rat milk substitute; BCFA, hand-fed rat milk substitute with 20%w/w BCFA. Total fat was equivalent (11%wt) for both the Control and BCFA groups. Cecal microbiota were characterized by 16S rRNA gene pyrosequencing, and intestinal injury, ileal cytokine and mucin gene expression, interleukin-10 (IL-10) peptide immunohistochemistry, and BCFA uptake in ileum phospholipids, serum and liver were assessed.
  
  
  RESULTS
  NEC incidence was reduced by over 50% in the BCFA group compared to the Control group as assessed in ileal tissue; microbiota differed among all groups. BCFA-fed pups harbored greater levels of BCFA-associated Bacillus subtilis and Pseudomonas aeruginosa compared to Controls. Bacillus subtilis levels were five-fold greater in healthy pups compared to pups with NEC. BCFA were selectively incorporated into ileal phospholipids, serum and liver tissue. IL-10 expression increased three-fold in the BCFA group versus Controls and no other inflammatory or mucosal mRNA markers changed.
  
  
  CONCLUSIONS
  At constant dietary fat level, BCFA reduce NEC incidence and alter microbiota composition. BCFA are also incorporated into pup ileum where they are associated with enhanced IL-10 and may exert other specific effects.
authors.affiliation: Division of Nutritional Sciences, Savage Hall, Cornell University, Ithaca, New York, United States of America.
authors.forename: Rinat R
authors.initials: RR
authors.lastname: Ran-Ressler
authors.forename: Ludmila
authors.initials: L
authors.lastname: Khailova
authors.forename: Kelly M
authors.initials: KM
authors.lastname: Arganbright
authors.forename: Camille K
authors.initials: CK
authors.lastname: Adkins-Rieck
authors.forename: Zeina E
authors.initials: ZE
authors.lastname: Jouni
authors.forename: Omry
authors.initials: O
authors.lastname: Koren
authors.forename: Ruth E
authors.initials: RE
authors.lastname: Ley
authors.forename: J Thomas
authors.initials: JT
authors.lastname: Brenna
authors.forename: Bohuslav
authors.initials: B
authors.lastname: Dvorak
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D001419:Bacteria / Q000187:drug effects* / Q000235:genetics; D002849:Chromatography, Gas; D004032:Diet; D004195:Disease Models, Animal; D020345:Enterocolitis, Necrotizing / Q000188:drug therapy* / Q000235:genetics / Q000382:microbiology*; D005227:Fatty Acids / Q000097:blood / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use*; D041981:Gastrointestinal Tract / Q000187:drug effects* / Q000378:metabolism / Q000382:microbiology* / Q000473:pathology; D005786:Gene Expression Regulation / Q000187:drug effects; D014644:Genetic Variation / Q000187:drug effects; D006262:Health; D007082:Ileum / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D007150:Immunohistochemistry; D015994:Incidence; D016753:Interleukin-10 / Q000235:genetics / Q000378:metabolism; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D009077:Mucins / Q000235:genetics / Q000378:metabolism; D009479:Neuropeptides / Q000235:genetics / Q000378:metabolism; D010455:Peptides / Q000378:metabolism; D010743:Phospholipids / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D000071165:Trefoil Factor-3
chemical_list: D005227:Fatty Acids; D009077:Mucins; D009479:Neuropeptides; D010455:Peptides; D010743:Phospholipids; D012333:RNA, Messenger; C099037:TFF3 protein, rat; D000071165:Trefoil Factor-3; D016753:Interleukin-10