Frontline Science: Tryptophan restriction arrests B cell development and enhances microbial diversity in WT and prematurely aging Ercc1-/Δ7 mice

Adriaan A van Beek, Floor Hugenholtz, Ben Meijer, Bruno Sovran, Olaf Perdijk, Wilbert P Vermeij, Renata M C Brandt, Sander Barnhoorn, Jan H J Hoeijmakers, Paul de Vos, Pieter J M Leenen, Rudi W Hendriks, Huub F J Savelkoul

Research output: Contribution to journalArticlepeer-review

22 Citations (Scopus)


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-old Ercc1-/Δ7 mice 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, old Ercc1-/Δ7 mice 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 old Ercc1-/Δ7 mice 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.

Original languageEnglish
Pages (from-to)811-821
Number of pages11
JournalJournal of leukocyte biology
Issue number4
Publication statusPublished - Apr 2017
Externally publishedYes


  • Aging, Premature/immunology
  • Animals
  • B-Lymphocytes/cytology
  • Bacteria/metabolism
  • Bone Marrow/metabolism
  • DNA-Binding Proteins/metabolism
  • Diet
  • Endonucleases/metabolism
  • Female
  • Gastrointestinal Tract/microbiology
  • Immunologic Memory
  • Lymph Nodes/cytology
  • Lymphocyte Count
  • Mice, Inbred C57BL
  • Microbiota
  • Spleen/cytology
  • T-Lymphocytes, Regulatory/metabolism
  • Tryptophan/metabolism


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