title: The Human Milk Oligosaccharide 2'-Fucosyllactose Quenches Campylobacter jejuni-Induced Inflammation in Human Epithelial Cells HEp-2 and HT-29 and in Mouse Intestinal Mucosa.
abstract: BACKGROUND
  Campylobacter jejuni causes diarrhea worldwide; young children are most susceptible. Binding of virulent C. jejuni to the intestinal mucosa is inhibited ex vivo by α1,2-fucosylated carbohydrate moieties, including human milk oligosaccharides (HMOSs).
  
  
  OBJECTIVE
  The simplest α1,2-fucosylated HMOS structure, 2'-fucosyllactose (2'-FL), can be predominant at ≤5 g/L milk. Although 2'-FL inhibits C. jejuni binding ex vivo and in vivo, the effects of 2'FL on the cell invasion central to C. jejuni pathogenesis have not been tested. Clinical isolates of C. jejuni infect humans, birds, and ferrets, limiting studies on its mammalian pathobiology.
  
  
  METHODS
  Human epithelial cells HEp-2 and HT-29 infected with the virulent C. jejuni strain 81-176 human isolate were treated with 5 g 2'-FL/L, and the degree of infection and inflammatory response was measured. Four-week-old male wild-type C57BL/6 mice were fed antibiotics to reduce their intestinal microbiota and were inoculated with C. jejuni strain 81-176. The sensitivity of the resulting acute transient enteric infection and immune response to inhibition by 2'-FL ingestion was tested.
  
  
  RESULTS
  In HEp-2 and HT-29 cells, 2'-FL attenuated 80% of C. jejuni invasion (P < 0.05) and suppressed the release of mucosal proinflammatory signals of interleukin (IL) 8 by 60-70%, IL-1β by 80-90%, and the neutrophil chemoattractant macrophage inflammatory protein 2 (MIP-2) by 50% (P < 0.05). Ingestion of 2'-FL by mice reduced C. jejuni colonization by 80%, weight loss by 5%, histologic features of intestinal inflammation by 50-70%, and induction of inflammatory signaling molecules of the acute-phase mucosal immune response by 50-60% (P < 0.05). This acute model did not induce IL-17 (adaptive T cell response), a chronic response.
  
  
  CONCLUSIONS
  In human cells in vitro (HEp-2, HT-29) and in a mouse infection model that recapitulated key pathologic features of C. jejuni clinical disease, 2'-FL inhibited pathogenesis and its sequelae. These data strongly support the hypothesis that 2'-FL represents a new class of oral agent for prevention, and potentially for treatment, of specific enteric infectious diseases.
authors.affiliation: Department of Biology, Boston College, Chestnut Hill, MA; and.
authors.forename: Zhuo-Teng
authors.initials: ZT
authors.lastname: Yu
authors.affiliation: Department of Biomedical Sciences and Pathobiology, Virginia Polytechnic Institute and State University, Blacksburg, VA.
authors.forename: N Nanda
authors.initials: NN
authors.lastname: Nanthakumar
authors.affiliation: Department of Biology, Boston College, Chestnut Hill, MA; and dnewburg1@gmail.com.
authors.forename: David S
authors.identifier: http://orcid.org/0000-0001-6042-7303
authors.initials: DS
authors.lastname: Newburg
mesh_terms: D000818:Animals; D002169:Campylobacter Infections / Q000517:prevention & control*; D016123:Campylobacter jejuni / Q000472:pathogenicity*; D045744:Cell Line, Tumor; D054426:Chemokine CXCL2 / Q000378:metabolism; D004195:Disease Models, Animal; D004847:Epithelial Cells / Q000166:cytology* / Q000378:metabolism / Q000382:microbiology; D000069196:Gastrointestinal Microbiome; D019073:HT29 Cells; D006801:Humans; D007249:Inflammation / Q000382:microbiology / Q000517:prevention & control; D053583:Interleukin-1beta / Q000378:metabolism; D016209:Interleukin-8 / Q000378:metabolism; D007413:Intestinal Mucosa / Q000378:metabolism / Q000382:microbiology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008895:Milk, Human / Q000737:chemistry*; D012333:RNA, Messenger / Q000378:metabolism; D014312:Trisaccharides / Q000008:administration & dosage*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D054426:Chemokine CXCL2; D053583:Interleukin-1beta; D016209:Interleukin-8; D012333:RNA, Messenger; D014312:Trisaccharides; D014409:Tumor Necrosis Factor-alpha; C031420:2'-fucosyllactose
keywords: cytokines; enteric infection; human milk oligosaccharides; inflammation; mucosal immune response