Tryptophan restriction arrests B cell development and enhances microbial diversity in WT and prematurely aging Ercc1−/Δ7 mice

A.A. van Beek*, F. Hugenholtz, B. Meijer, B. Sovran, O.I.J. Perdijk, W. Vermeij, R.M. Brandt, R. Barnhoorn, Jan H.J. Hoeijmakers, P. de Vos, P.J. Leenen, R.W. Hendriks, H.F.J. Savelkoul

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

11 Citations (Scopus)

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.
Original languageEnglish
Pages (from-to)811-821
JournalJournal of Leukocyte Biology
Volume101
Issue number4
DOIs
Publication statusPublished - 2017

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