title: Supplementation with galacto-oligosaccharides increases the percentage of NK cells and reduces colitis severity in Smad3-deficient mice.
abstract: The gut microbiota plays an essential role in intestinal immunity. Prebiotics, including galacto-oligosaccharides (GOS), are fermentable fibers that beneficially affect the host by stimulating the growth of specific microbial populations. We investigated the effect of GOS on colitis development and on immune variables in Smad3-deficient mice treated with the pathogen Helicobacter hepaticus. Mice were supplemented daily with 5000 mg GOS/kg body weight 2 wk prior to infection and 4 wk postinfection, a time period during which colitis severity peaks in this model. Mice (n = 4-8/treatment at each time) were killed preinfection (0 d) and at 3, 7, and 28 d postinfection to evaluate immune variables in the spleen and in mesenteric lymph nodes (MsLN) by flow cytometry. Colon and cecum samples were collected for histopathologic analysis. Fecal pellets (n = 8-9/treatment) were collected prior to infection to measure relative changes in Bifidobacterium ssp. and Lactobacillum ssp. by real-time PCR. GOS significantly reduced colitis severity in response to H. hepaticus (P < 0.0001). This was associated with a significant increase in the percentage of NK cells in the spleen (P < 0.001) and in MsLN (P < 0.001) at 3 d postinfection and a 1.5-fold increase in fecal Bifidobacterium ssp. (P = 0.003). GOS stimulated NK expression of CCR9, a chemokine receptor involved in lymphocyte trafficking to the gut preinfection (0 d) in the blood (P = 0.02), spleen (P = 0.033), and MsLN (P = 0.017). In addition, GOS stimulated colonic IL-15 production 3 d postinfection (P < 0.001). These data suggest that GOS reduces colitis by modulating the function and trafficking of NK cells and may provide a novel therapeutic strategy for individuals with inflammatory bowel disease.
authors.affiliation: Department of Food Science and Human Nutrition, Michigan State University, East Lansing, MI, USA.
authors.forename: Anita
authors.initials: A
authors.lastname: Gopalakrishnan
authors.forename: Jonathan F
authors.initials: JF
authors.lastname: Clinthorne
authors.forename: Elizabeth A
authors.initials: EA
authors.lastname: Rondini
authors.forename: Sarah J
authors.initials: SJ
authors.lastname: McCaskey
authors.forename: Eric A
authors.initials: EA
authors.lastname: Gurzell
authors.forename: Ingeborg M
authors.initials: IM
authors.lastname: Langohr
authors.forename: Elizabeth M
authors.initials: EM
authors.lastname: Gardner
authors.forename: Jenifer I
authors.initials: JI
authors.lastname: Fenton
mesh_terms: D000818:Animals; D001644:Bifidobacterium / Q000187:drug effects*; D002432:Cecum / Q000187:drug effects / Q000276:immunology / Q000382:microbiology; D003092:Colitis / Q000188:drug therapy* / Q000235:genetics / Q000276:immunology / Q000382:microbiology; D003106:Colon / Q000187:drug effects* / Q000276:immunology / Q000382:microbiology; D004043:Dietary Fiber / Q000494:pharmacology / Q000627:therapeutic use; D005243:Feces / Q000382:microbiology; D005690:Galactose / Q000494:pharmacology / Q000627:therapeutic use; D016481:Helicobacter Infections / Q000188:drug therapy / Q000235:genetics / Q000276:immunology / Q000382:microbiology; D044923:Helicobacter hepaticus; D019409:Interleukin-15 / Q000378:metabolism; D007694:Killer Cells, Natural / Q000187:drug effects*; D007778:Lactobacillus / Q000187:drug effects; D008198:Lymph Nodes / Q000187:drug effects; D008643:Mesentery / Q000187:drug effects / Q000276:immunology; D000090204:Mesothelin; D051379:Mice; D018345:Mice, Knockout; D009844:Oligosaccharides / Q000494:pharmacology / Q000627:therapeutic use*; D056692:Prebiotics; D060888:Real-Time Polymerase Chain Reaction; D054388:Receptors, CCR / Q000378:metabolism; D012720:Severity of Illness Index; D051900:Smad3 Protein / Q000235:genetics*; D013154:Spleen / Q000187:drug effects / Q000276:immunology
chemical_list: D004043:Dietary Fiber; D019409:Interleukin-15; C000715527:MSLN protein, human; C000715528:Msln protein, mouse; D009844:Oligosaccharides; D056692:Prebiotics; D054388:Receptors, CCR; D051900:Smad3 Protein; C497791:Smad3 protein, mouse; D000090204:Mesothelin; D005690:Galactose