title: Frontline Science: Tryptophan restriction arrests B cell development and enhances microbial diversity in WT and prematurely agingErcc1-/Δ7mice.
abstract: With aging, tryptophan metabolism is affected. Tryptophan has a crucial role in the induction of immune tolerance and the maintenance of gut microbiota. We, therefore, studied the effect of dietary tryptophan restriction in young wild-type (WT) mice (118-wk life span) and in DNA-repair deficient, premature-aged (Ercc1-/Δ7) mice (20-wk life span). First, we found that the effect of aging on the distribution of B and T cells in bone marrow (BM) and in the periphery of 16-wk-oldErcc1-/Δ7mice was comparable to that in 18-mo-old WT mice. Dietary tryptophan restriction caused an arrest of B cell development in the BM, accompanied by diminished B cell frequencies in the periphery. In general, oldErcc1-/Δ7mice showed similar responses to tryptophan restriction compared with young WT mice, indicative of age-independent effects. Dietary tryptophan restriction increased microbial diversity and made the gut microbiota composition of oldErcc1-/Δ7mice more similar to that of young WT mice. The decreased abundances of Alistipes and Akkermansia spp. after dietary tryptophan restriction correlated significantly with decreased B cell precursor numbers. In conclusion, we report that dietary tryptophan restriction arrests B cell development and concomitantly changes gut microbiota composition. Our study suggests a beneficial interplay between dietary tryptophan, B cell development, and gut microbial composition on several aspects of age-induced changes.
authors.affiliation: Top Institute Food and Nutrition, Wageningen, The Netherlands; a.vanbeek@erasmusmc.nl.|Cell Biology and Immunology Group, Wageningen University, Wageningen, The Netherlands.|Department of Immunology, Erasmus University Medical Center, Rotterdam, The Netherlands.
authors.forename: Adriaan A
authors.initials: AA
authors.lastname: van Beek
authors.affiliation: Top Institute Food and Nutrition, Wageningen, The Netherlands.|Laboratory of Microbiology, Wageningen University, Wageningen, The Netherlands.
authors.forename: Floor
authors.initials: F
authors.lastname: Hugenholtz
authors.affiliation: Cell Biology and Immunology Group, Wageningen University, Wageningen, The Netherlands.
authors.forename: Ben
authors.initials: B
authors.lastname: Meijer
authors.affiliation: Top Institute Food and Nutrition, Wageningen, The Netherlands.|Host-Microbe Interactomics Group, Wageningen University, Wageningen, The Netherlands.
authors.forename: Bruno
authors.initials: B
authors.lastname: Sovran
authors.affiliation: Cell Biology and Immunology Group, Wageningen University, Wageningen, The Netherlands.
authors.forename: Olaf
authors.initials: O
authors.lastname: Perdijk
authors.affiliation: Department of Molecular Genetics, Erasmus University Medical Center, Rotterdam, The Netherlands.
authors.forename: Wilbert P
authors.initials: WP
authors.lastname: Vermeij
authors.affiliation: Department of Molecular Genetics, Erasmus University Medical Center, Rotterdam, The Netherlands.
authors.forename: Renata M C
authors.initials: RM
authors.lastname: Brandt
authors.affiliation: Department of Molecular Genetics, Erasmus University Medical Center, Rotterdam, The Netherlands.
authors.forename: Sander
authors.initials: S
authors.lastname: Barnhoorn
authors.affiliation: Department of Molecular Genetics, Erasmus University Medical Center, Rotterdam, The Netherlands.
authors.forename: Jan H J
authors.initials: JH
authors.lastname: Hoeijmakers
authors.affiliation: Top Institute Food and Nutrition, Wageningen, The Netherlands.|Pathology and Medical Biology, University of Groningen, Groningen, The Netherlands; and.
authors.forename: Paul
authors.initials: P
authors.lastname: de Vos
authors.affiliation: Department of Immunology, Erasmus University Medical Center, Rotterdam, The Netherlands.
authors.forename: Pieter J M
authors.initials: PJ
authors.lastname: Leenen
authors.affiliation: Department of Pulmonary Medicine, Erasmus University Medical Center, Rotterdam, The Netherlands.
authors.forename: Rudi W
authors.initials: RW
authors.lastname: Hendriks
authors.affiliation: Cell Biology and Immunology Group, Wageningen University, Wageningen, The Netherlands.
authors.forename: Huub F J
authors.initials: HF
authors.lastname: Savelkoul
mesh_terms: D019588:Aging, Premature / Q000276:immunology* / Q000382:microbiology*; D000818:Animals; D001402:B-Lymphocytes / Q000166:cytology*; D001419:Bacteria / Q000378:metabolism; D001853:Bone Marrow / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000378:metabolism*; D004032:Diet; D004720:Endonucleases / Q000378:metabolism*; D005260:Female; D041981:Gastrointestinal Tract / Q000382:microbiology; D007156:Immunologic Memory; D008198:Lymph Nodes / Q000166:cytology; D018655:Lymphocyte Count; D008810:Mice, Inbred C57BL; D064307:Microbiota; D013154:Spleen / Q000166:cytology; D050378:T-Lymphocytes, Regulatory / Q000378:metabolism; D014364:Tryptophan / Q000378:metabolism*
chemical_list: D004268:DNA-Binding Proteins; D014364:Tryptophan; D004720:Endonucleases; C499360:Ercc1 protein, mouse
keywords: bone marrow; gut microbiota; hematopoiesis; proliferation