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

Onderzoeksoutput: Bijdrage aan tijdschriftArtikelpeer review

17 Citaten (Scopus)

Samenvatting

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.

Originele taal-2Engels
Pagina's (van-tot)811-821
Aantal pagina's11
TijdschriftJournal of leukocyte biology
Volume101
Nummer van het tijdschrift4
DOI's
StatusGepubliceerd - apr. 2017
Extern gepubliceerdJa

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