title: Gut microbiota metabolism of dietary fiber influences allergic airway disease and hematopoiesis.
abstract: Metabolites from intestinal microbiota are key determinants of host-microbe mutualism and, consequently, the health or disease of the intestinal tract. However, whether such host-microbe crosstalk influences inflammation in peripheral tissues, such as the lung, is poorly understood. We found that dietary fermentable fiber content changed the composition of the gut and lung microbiota, in particular by altering the ratio of Firmicutes to Bacteroidetes. The gut microbiota metabolized the fiber, consequently increasing the concentration of circulating short-chain fatty acids (SCFAs). Mice fed a high-fiber diet had increased circulating levels of SCFAs and were protected against allergic inflammation in the lung, whereas a low-fiber diet decreased levels of SCFAs and increased allergic airway disease. Treatment of mice with the SCFA propionate led to alterations in bone marrow hematopoiesis that were characterized by enhanced generation of macrophage and dendritic cell (DC) precursors and subsequent seeding of the lungs by DCs with high phagocytic capacity but an impaired ability to promote T helper type 2 (TH2) cell effector function. The effects of propionate on allergic inflammation were dependent on G protein-coupled receptor 41 (GPR41, also called free fatty acid receptor 3 or FFAR3), but not GPR43 (also called free fatty acid receptor 2 or FFAR2). Our results show that dietary fermentable fiber and SCFAs can shape the immunological environment in the lung and influence the severity of allergic inflammation.
authors.affiliation: Faculty of Biology and Medicine, University of Lausanne, Service de Pneumologie, BH19.206 Centre Hospitalier Universitaire Vaudois (CHUV), Lausanne, Switzerland.
authors.forename: Aurélien
authors.initials: A
authors.lastname: Trompette
authors.affiliation: Faculty of Biology and Medicine, University of Lausanne, Service de Pneumologie, BH19.206 Centre Hospitalier Universitaire Vaudois (CHUV), Lausanne, Switzerland.
authors.forename: Eva S
authors.initials: ES
authors.lastname: Gollwitzer
authors.affiliation: Faculty of Biology and Medicine, University of Lausanne, Service de Pneumologie, BH19.206 Centre Hospitalier Universitaire Vaudois (CHUV), Lausanne, Switzerland.
authors.forename: Koshika
authors.initials: K
authors.lastname: Yadava
authors.affiliation: Faculty of Biology and Medicine, University of Lausanne, Service de Pneumologie, BH19.206 Centre Hospitalier Universitaire Vaudois (CHUV), Lausanne, Switzerland.
authors.forename: Anke K
authors.initials: AK
authors.lastname: Sichelstiel
authors.affiliation: Nutrition and Health Research, Nestlé Research Center, Lausanne, Switzerland.
authors.forename: Norbert
authors.initials: N
authors.lastname: Sprenger
authors.affiliation: Nutrition and Health Research, Nestlé Research Center, Lausanne, Switzerland.
authors.forename: Catherine
authors.initials: C
authors.lastname: Ngom-Bru
authors.affiliation: Nutrition and Health Research, Nestlé Research Center, Lausanne, Switzerland.
authors.forename: Carine
authors.initials: C
authors.lastname: Blanchard
authors.affiliation: Novartis Pharma AG, Basel, Switzerland.
authors.forename: Tobias
authors.initials: T
authors.lastname: Junt
authors.affiliation: Faculty of Biology and Medicine, University of Lausanne, Service de Pneumologie, BH19.206 Centre Hospitalier Universitaire Vaudois (CHUV), Lausanne, Switzerland.
authors.forename: Laurent P
authors.initials: LP
authors.lastname: Nicod
authors.affiliation: Global Health Institute, École Polytechnique Fédérale de Lausanne (EPFL)-SV-Global Health Institute (GHI) Station 19, EPFL, Lausanne, Switzerland.
authors.forename: Nicola L
authors.initials: NL
authors.lastname: Harris
authors.affiliation: Faculty of Biology and Medicine, University of Lausanne, Service de Pneumologie, BH19.206 Centre Hospitalier Universitaire Vaudois (CHUV), Lausanne, Switzerland.
authors.forename: Benjamin J
authors.identifier: 0000000314573160
authors.initials: BJ
authors.lastname: Marsland
mesh_terms: D019264:Adoptive Transfer; D000818:Animals; D041963:Bacteroidetes / Q000378:metabolism*; D001483:Base Sequence; D016207:Cytokines / Q000378:metabolism; D017931:DNA Primers / Q000235:genetics; D004269:DNA, Bacterial / Q000302:isolation & purification; D004043:Dietary Fiber / Q000382:microbiology*; D004797:Enzyme-Linked Immunosorbent Assay; D005227:Fatty Acids / Q000097:blood; D005243:Feces / Q000737:chemistry; D005260:Female; D005434:Flow Cytometry; D006410:Hematopoiesis / Q000502:physiology*; D006967:Hypersensitivity / Q000503:physiopathology*; D007422:Intestines / Q000382:microbiology*; D008168:Lung / Q000737:chemistry / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D064307:Microbiota / Q000502:physiology*; D008969:Molecular Sequence Data; D060888:Real-Time Polymerase Chain Reaction; D017422:Sequence Analysis, DNA; D018709:Statistics, Nonparametric
chemical_list: D016207:Cytokines; D017931:DNA Primers; D004269:DNA, Bacterial; D004043:Dietary Fiber; D005227:Fatty Acids