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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\u2212\/\u03947) 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\u2212\/\u03947 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\u2212\/\u03947 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\u2212\/\u03947 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.<\/jats:p>","DOI":"10.1189\/jlb.1hi0216-062rr","type":"journal-article","created":{"date-parts":[[2016,7,15]],"date-time":"2016-07-15T02:03:44Z","timestamp":1468548224000},"page":"811-821","source":"Crossref","is-referenced-by-count":33,"title":["Frontline Science: Tryptophan restriction arrests B cell development and enhances microbial diversity in WT and prematurely aging <i>Ercc1\u2212\/\u03947<\/i> mice"],"prefix":"10.1093","volume":"101","author":[{"given":"Adriaan A","family":"van Beek","sequence":"first","affiliation":[{"name":"Top Institute Food and Nutrition , Wageningen , The Netherlands"},{"name":"Cell Biology and Immunology Group, Wageningen University , Wageningen , The Netherlands"},{"name":"Department of Immunology, Erasmus University Medical Center , Rotterdam , The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Floor","family":"Hugenholtz","sequence":"additional","affiliation":[{"name":"Top Institute Food and Nutrition , Wageningen , The Netherlands"},{"name":"Laboratory of Microbiology, Wageningen University , Wageningen , The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ben","family":"Meijer","sequence":"additional","affiliation":[{"name":"Cell Biology and Immunology Group, Wageningen University , Wageningen , The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bruno","family":"Sovran","sequence":"additional","affiliation":[{"name":"Top Institute Food and Nutrition , Wageningen , The Netherlands"},{"name":"Host-Microbe Interactomics Group, Wageningen University , Wageningen , The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Olaf","family":"Perdijk","sequence":"additional","affiliation":[{"name":"Cell Biology and Immunology Group, Wageningen University , Wageningen , The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wilbert P","family":"Vermeij","sequence":"additional","affiliation":[{"name":"Department of Molecular Genetics, Erasmus University Medical Center , Rotterdam , The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Renata M C","family":"Brandt","sequence":"additional","affiliation":[{"name":"Department of Molecular Genetics, Erasmus University Medical Center , Rotterdam , The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sander","family":"Barnhoorn","sequence":"additional","affiliation":[{"name":"Department of Molecular Genetics, Erasmus University Medical Center , Rotterdam , The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jan H J","family":"Hoeijmakers","sequence":"additional","affiliation":[{"name":"Department of Molecular Genetics, Erasmus University Medical Center , Rotterdam , The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paul","family":"de Vos","sequence":"additional","affiliation":[{"name":"Top Institute Food and Nutrition , Wageningen , The Netherlands"},{"name":"Pathology and Medical Biology, University of Groningen , Groningen , The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pieter J M","family":"Leenen","sequence":"additional","affiliation":[{"name":"Department of Immunology, Erasmus University Medical Center , Rotterdam , The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rudi W","family":"Hendriks","sequence":"additional","affiliation":[{"name":"Department of Pulmonary Medicine, Erasmus University Medical Center , Rotterdam , The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huub F J","family":"Savelkoul","sequence":"additional","affiliation":[{"name":"Cell Biology and Immunology Group, Wageningen University , Wageningen , The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2016,7,14]]},"reference":[{"key":"2023011712063261500_B1","doi-asserted-by":"crossref","first-page":"e201","DOI":"10.1371\/journal.pbio.0050201","article-title":"Aging hematopoietic stem cells decline in function and exhibit epigenetic dysregulation","volume":"5","author":"Chambers","year":"2007","journal-title":"PLoS Biol."},{"key":"2023011712063261500_B2","doi-asserted-by":"crossref","first-page":"9194","DOI":"10.1073\/pnas.0503280102","article-title":"Cell intrinsic alterations underlie hematopoietic stem cell aging","volume":"102","author":"Rossi","year":"2005","journal-title":"Proc. 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Immunol."},{"key":"2023011712063261500_B39","doi-asserted-by":"crossref","first-page":"119","DOI":"10.1111\/j.1474-9726.2005.00152.x","article-title":"Methionine-deficient diet extends mouse lifespan, slows immune and lens aging, alters glucose, T4, IGF-I and insulin levels, and increases hepatocyte MIF levels and stress resistance","volume":"4","author":"Miller","year":"2005","journal-title":"Aging Cell"},{"key":"2023011712063261500_B40","doi-asserted-by":"crossref","first-page":"183","DOI":"10.1007\/s10522-008-9130-1","article-title":"Forty percent and eighty percent methionine restriction decrease mitochondrial ROS generation and oxidative stress in rat liver","volume":"9","author":"Caro","year":"2008","journal-title":"Biogerontology"},{"key":"2023011712063261500_B41","doi-asserted-by":"crossref","first-page":"1064","DOI":"10.1096\/fj.05-5568com","article-title":"Methionine restriction decreases mitochondrial oxygen radical generation and leak as well as oxidative damage to mitochondrial DNA and proteins","volume":"20","author":"Sanz","year":"2006","journal-title":"FASEB J."},{"key":"2023011712063261500_B42","doi-asserted-by":"crossref","first-page":"R728","DOI":"10.1152\/ajpregu.00837.2009","article-title":"Dietary methionine restriction enhances metabolic flexibility and increases uncoupled respiration in both fed and fasted states","volume":"299","author":"Hasek","year":"2010","journal-title":"Am. J. Physiol. Regul. Integr. Comp. Physiol."},{"key":"2023011712063261500_B43","doi-asserted-by":"crossref","first-page":"5091","DOI":"10.4049\/jimmunol.171.10.5091","article-title":"Adiponectin, a fat cell product, influences the earliest lymphocyte precursors in bone marrow cultures by activation of the cyclooxygenase-prostaglandin pathway in stromal cells","volume":"171","author":"Yokota","year":"2003","journal-title":"J. Immunol."},{"key":"2023011712063261500_B44","doi-asserted-by":"crossref","first-page":"528","DOI":"10.1016\/j.cmet.2011.08.014","article-title":"Nicotinamide mononucleotide, a key NAD+ intermediate, treats the pathophysiology of diet- and age-induced diabetes in mice","volume":"14","author":"Yoshino","year":"2011","journal-title":"Cell Metab."},{"key":"2023011712063261500_B45","doi-asserted-by":"crossref","first-page":"18","DOI":"10.1111\/j.0105-2896.2005.00269.x","article-title":"The aging of early B-cell precursors","volume":"205","author":"Allman","year":"2005","journal-title":"Immunol. 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Invest."},{"key":"2023011712063261500_B48","first-page":"1431","article-title":"Cloning and characterization of the cDNA encoding a novel human pre-B-cell colony-enhancing factor","volume":"14","author":"Samal","year":"1994","journal-title":"Mol. Cell. Biol."},{"key":"2023011712063261500_B49","doi-asserted-by":"crossref","first-page":"247","DOI":"10.1007\/s11357-011-9217-5","article-title":"Ageing of the human metaorganism: the microbial counterpart","volume":"34","author":"Biagi","year":"2011","journal-title":"Age (Dordr)"},{"key":"2023011712063261500_B50","doi-asserted-by":"crossref","first-page":"7767","DOI":"10.1128\/AEM.01477-07","article-title":"Intestinal integrity and Akkermansia muciniphila, a mucindegrading member of the intestinal microbiota present in infants, adults, and the elderly.) Intestinal integrity and Akkermansia muciniphila, a mucindegrading member of the intestinal microbiota present in infants, adults, and the elderly","volume":"73","author":"Collado","year":"2007","journal-title":"Appl. Environ. Microbiol."},{"key":"2023011712063261500_B51","doi-asserted-by":"crossref","first-page":"9066","DOI":"10.1073\/pnas.1219451110","article-title":"Cross-talk between Akkermansia muciniphila and intestinal epithelium controls diet-induced obesity","volume":"110","author":"Everard","year":"2013","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"2023011712063261500_B52","doi-asserted-by":"crossref","first-page":"193ra91","DOI":"10.1126\/scitranslmed.3006438","article-title":"Dysbiosis of the gut microbiota is associated with HIV disease progression and tryptophan catabolism","volume":"5","author":"Vujkovic-Cvijin","year":"2013","journal-title":"Sci. Transl. Med."},{"key":"2023011712063261500_B53","doi-asserted-by":"crossref","first-page":"13780","DOI":"10.1073\/pnas.0706625104","article-title":"Molecular-phylogenetic characterization of microbial community imbalances in human inflammatory bowel diseases","volume":"104","author":"Frank","year":"2007","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"2023011712063261500_B54","doi-asserted-by":"crossref","first-page":"47","DOI":"10.1016\/j.clim.2004.05.004","article-title":"Overexpression of indoleamine 2,3-dioxygenase in human inflammatory bowel disease","volume":"113","author":"Wolf","year":"2004","journal-title":"Clin. Immunol."},{"key":"2023011712063261500_B55","doi-asserted-by":"crossref","first-page":"10177","DOI":"10.1007\/s00253-014-6053-4","article-title":"Analysis of the tryptophanase expression in Symbiobacterium thermophilum in a coculture with Geobacillus stearothermophilus","volume":"98","author":"Watsuji","year":"2014","journal-title":"Appl. Microbiol. 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