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

Journal of Leukocyte Biology: An Official Publication of the Reticuloendothelial Society

Sovran, Bruno¹  Vos, Paul¹  Vermeij, Wilbert P.¹  Hendriks, Rudi W.¹  Barnhoorn, Sander³  Meijer, Ben⁴  Leenen, Pieter J. M.⁶  Perdijk, Olaf⁶  Savelkoul, Huub F. J.⁸  Hoeijmakers, Jan H. J.^1,10  Hugenholtz, Floor^1,11  Brandt, Renata M. C.^1,11 

[1] and;..Host‐..Laboratory of Microbiology, Wageningen University, Wageningen, The Netherlands;..Pathology and Medical Biology, University of Groningen, Groningen, The Netherlands;Cell Biology and Immunology Group, Wageningen University, Wageningen, The Netherlands;Department of Immunology, Erasmus University Medical Center, Rotterdam, The Netherlands;Department of Molecular Genetics, Erasmus University Medical Center, Rotterdam, The Netherlands;Department of Pulmonary Medicine, Erasmus University Medical Center, Rotterdam, The Netherlands;Microbe Interactomics Group, Wageningen University, Wageningen, The Netherlands;Top Institute Food and Nutrition, Wageningen, The Netherlands

关键词: bone marrow;    gut microbiota;    hematopoiesis;    proliferation;   

学科分类：生理学

来源: Federation of American Societies for Experimental Biology

【 摘 要 】

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.

【 授权许可】

CC BY