title: β2→1-Fructans Modulate the Immune SystemIn Vivoin a Microbiota-Dependent and -Independent Fashion.
abstract: It has been shownin vitrothat only specific dietary fibers contribute to immunity, but studiesin vivoare not conclusive. Here, we investigated degree of polymerization (DP) dependent effects of β2→1-fructans on immunityviamicrobiota-dependent and -independent effects. To this end, conventional or germ-free mice received short- or long-chain β2→1-fructan for 5 days. Immune cell populations in the spleen, mesenteric lymph nodes (MLNs), and Peyer's patches (PPs) were analyzed with flow cytometry, genome-wide gene expression in the ileum was measured with microarray, and gut microbiota composition was analyzed with 16S rRNA sequencing of fecal samples. We found that β2→1-fructans modulated immunity by both microbiota and microbiota-independent effects. Moreover, effects were dependent on the chain-length of the β2→1-fructans type polymer. Both short- and long-chain β2→1-fructans enhanced T-helper 1 cells in PPs, whereas only short-chain β2→1-fructans increased regulatory T cells and CD11b-CD103-dendritic cells (DCs) in the MLN. A common feature after short- and long-chain β2→1-fructan treatment was enhanced 2-alpha-l-fucosyltransferase 2 expression and other IL-22-dependent genes in the ileum of conventional mice. These effects were not associated with shifts in gut microbiota composition, or altered production of short-chain fatty acids. Both short- and long-chain β2→1-fructans also induced immune effects in germ-free animals, demonstrating direct effect independent from the gut microbiota. Also, these effects were dependent on the chain-length of the β2→1-fructans. Short-chain β2→1-fructan induced lower CD80 expression by CD11b-CD103-DCs in PPs, whereas long-chain β2→1-fructan specifically modulated B cell responses in germ-free mice. In conclusion, support of immunity is determined by the chemical structure of β2→1-fructans and is partially microbiota independent.
authors.affiliation: Top Institute Food and Nutrition, Wageningen, Netherlands; Department of Pathology and Medical Biology, University Medical Center Groningen, University of Groningen, Groningen, Netherlands.
authors.forename: Floris
authors.initials: F
authors.lastname: Fransen
authors.affiliation: Department of Pathology and Medical Biology, University Medical Center Groningen, University of Groningen , Groningen , Netherlands.
authors.forename: Neha M
authors.initials: NM
authors.lastname: Sahasrabudhe
authors.affiliation: Top Institute Food and Nutrition, Wageningen, Netherlands; Department of Pathology and Medical Biology, University Medical Center Groningen, University of Groningen, Groningen, Netherlands.
authors.forename: Marlies
authors.initials: M
authors.lastname: Elderman
authors.affiliation: Laboratory of Food Chemistry, Wageningen University , Wageningen , Netherlands.
authors.forename: Margaret
authors.initials: M
authors.lastname: Bosveld
authors.affiliation: Microbial Physiology, Groningen Biomolecular Sciences and Biotechnology Institute (GBB), University of Groningen , Groningen , Netherlands.
authors.forename: Sahar
authors.initials: S
authors.lastname: El Aidy
authors.affiliation: Top Institute Food and Nutrition, Wageningen, Netherlands; Laboratory of Microbiology, Wageningen University, Wageningen, Netherlands.
authors.forename: Floor
authors.initials: F
authors.lastname: Hugenholtz
authors.affiliation: Department of Pathology and Medical Biology, University Medical Center Groningen, University of Groningen , Groningen , Netherlands.
authors.forename: Theo
authors.initials: T
authors.lastname: Borghuis
authors.affiliation: Department of Pathology and Medical Biology, University Medical Center Groningen, University of Groningen , Groningen , Netherlands.
authors.forename: Ben
authors.initials: B
authors.lastname: Kousemaker
authors.affiliation: Department of Pathology and Medical Biology, University Medical Center Groningen, University of Groningen , Groningen , Netherlands.
authors.forename: Simon
authors.initials: S
authors.lastname: Winkel
authors.affiliation: Laboratory of Pediatric Infectious Diseases, Radboud University Medical Center , Nijmegen , Netherlands.
authors.forename: Christa
authors.initials: C
authors.lastname: van der Gaast-de Jongh
authors.affiliation: Laboratory of Pediatric Infectious Diseases, Radboud University Medical Center , Nijmegen , Netherlands.
authors.forename: Marien I
authors.initials: MI
authors.lastname: de Jonge
authors.affiliation: Top Institute Food and Nutrition, Wageningen, Netherlands; Nutrition, Metabolism and Genomics Group, Division of Human Nutrition, Wageningen University, Wageningen, Netherlands.
authors.forename: Mark V
authors.initials: MV
authors.lastname: Boekschoten
authors.affiliation: Top Institute Food and Nutrition, Wageningen, Netherlands; Laboratory of Microbiology, Wageningen University, Wageningen, Netherlands.
authors.forename: Hauke
authors.initials: H
authors.lastname: Smidt
authors.affiliation: Top Institute Food and Nutrition, Wageningen, Netherlands; Laboratory of Food Chemistry, Wageningen University, Wageningen, Netherlands.
authors.forename: Henk A
authors.initials: HA
authors.lastname: Schols
authors.affiliation: Top Institute Food and Nutrition, Wageningen, Netherlands; Department of Pathology and Medical Biology, University Medical Center Groningen, University of Groningen, Groningen, Netherlands.
authors.forename: Paul
authors.initials: P
authors.lastname: de Vos
keywords: germ-free mice; gut microbiota; mucosal immunology; prebiotics; β2→1-fructans