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

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 ( ) 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 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 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 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.

Dietary Tryptophan Restriction Dose‐Dependently Modulates Energy Balance, Gut Hormones, and Microbiota in Obesity‐Prone Rats

“…The reduction in Bacteroides and Clostridium coccoides in our study was very likely a specific effect of tryptophan deficiency, and not secondary to tryptophan-induced hypophagia, because caloric restriction has been to shown to increase Bacteroides in humans (39). In contrast to our data, a recent study reported that fecal concentrations of Bacteroidetes RC9 and Clostridiales were increased by 90% tryptophan restriction in mice (20). In that study, the diet composition was not detailed, and the diets of both control and tryptophan-restricted mice appeared to contain basal 10% casein.…”

“…There is substantial evidence that tryptophan deficiency decreases food intake, feed efficiency, and growth rate in rodents and pigs (20,31). Consistent with these studies, we report that decreasing…”

“…There is emerging evidence that tryptophan metabolism by gut microbiota is important in several gut-brain disorders. For example, dietary tryptophan depletion worsened experimental autoimmune encephalomyelitis disease scores in mice (19), and a 95% reduction in dietary tryptophan arrested b-cell development, caused weight loss, and increased microbial diversity in mice (20). Furthermore, high-fat feeding resulted in gut microbial dysbiosis in rats (22), and we recently showed that diets enriched in whey protein components distinctly modulated select cecal gut bacteria in obese rats (7).…”

“…Dietary tryptophan is purported to modulate energy balance through multiple mechanisms, including alterations in central neural networks, secretion of gut hormones and serotonin, and modifications of gut microbiota composition (12,13,(18)(19)(20). Dietary deficiency of tryptophan, and reduction in its circulating concentrations, alter peripheral and central serotonin concentrations as well as permit greater transport of large neutral amino acids across the blood-brain barrier, which together are postulated to decrease food intake (11,12).…”

Editorial: No Trp, no B: surprising connectivity of diet, microbiome, aging, and adaptive immunity

“…The featured paper ("Tryptophan restriction arrests B cell development and enhances microbial diversity in WT and prematurely aging Ercc12/D7 mice") by van Beek et al [5] reduces the complexity of CR interventions by feeding mice a diet only lacking Trp, as TR also delays aging of mice. This study breaks new ground by evaluating the consequences of TR for B cell development.…”