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-/∆7) 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-/∆7 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-/∆7 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-/∆7 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.

Additional Metadata
Keywords Bone marrow, Gut microbiota, Hematopoiesis, Proliferation
Persistent URL dx.doi.org/10.1189/jlb.1HI0216-062RR, hdl.handle.net/1765/99181
Journal Journal of Leukocyte Biology
Rights No subscription
van Beek, A.A, Hugenholtz, F, Meijer, B, Sovran, B, Perdijk, O, Vermeij, W.P, … Savelkoul, H.F.J. (2017). Frontline science: Tryptophan restriction arrests B cell development and enhances microbial diversity in WT and prematurely aging Ercc1-/∆7 mice. Journal of Leukocyte Biology, 101(4), 811–821. doi:10.1189/jlb.1HI0216-062RR