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

J Leukoc Biol. 2017 Apr;101(4):811-821. doi: 10.1189/jlb.1HI0216-062RR. Epub 2016 Jul 14.

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-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.

Keywords: bone marrow; gut microbiota; hematopoiesis; proliferation.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, N.I.H., Extramural

MeSH terms

  • Aging, Premature / immunology*
  • Aging, Premature / microbiology*
  • 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*

Substances

  • DNA-Binding Proteins
  • Tryptophan
  • Endonucleases
  • Ercc1 protein, mouse