• 烟酰胺腺嘌呤二核苷酸(NAD)是人类生理重要辅酶,可由细菌中Toll/IL-1受体(TIR)蛋白结构域代谢;
  • 体外生化检测并筛选出孟加拉国婴幼儿肠道微生物组中152个TIR结构域及NADase酶活;
  • 体内采用TIRs多样性和NADase活性相关的26种人类肠道混合菌定植悉生小鼠,发现TIR NADase酶活特异产物v-cADPR-x,具显著的类群特异性和定植区别性;
  • 急性营养不良与可产生v-cADPR-x的TIR编码基因在粪便中的水平降低以及代谢物本身水平降低有关。
Jeffrey I. Gordon团队在Cell Reports上最新发表的文章,继续挖掘肠道菌群与营养不良的关系。这次他们解析了细菌Toll/IL-1受体(TIR)蛋白结构域对烟酰胺腺嘌呤二核苷酸的代谢,这一潜在的跨界通路对儿童营养不良的影响。
Cell Reports [IF:9.995]

Products of gut microbial Toll/interleukin-1 receptor domain NADase activities in gnotobiotic mice and Bangladeshi children with malnutrition



04-26, Article

Abstract & Authors:展开

Perturbed gut microbiome development has been linked to childhood malnutrition. Here, we characterize bacterial Toll/interleukin-1 receptor (TIR) protein domains that metabolize nicotinamide adenine dinucleotide (NAD), a co-enzyme with far-reaching effects on human physiology. A consortium of 26 human gut bacterial strains, representing the diversity of TIRs observed in the microbiome and the NAD hydrolase (NADase) activities of a subset of 152 bacterial TIRs assayed in vitro, was introduced into germ-free mice. Integrating mass spectrometry and microbial RNA sequencing (RNA-seq) with consortium membership manipulation disclosed that a variant of cyclic-ADPR (v-cADPR-x) is a specific product of TIR NADase activity and a prominent, colonization-discriminatory, taxon-specific metabolite. Guided by bioinformatic analyses of biochemically validated TIRs, we find that acute malnutrition is associated with decreased fecal levels of genes encoding TIRs known or predicted to generate v-cADPR-x, as well as decreased levels of the metabolite itself. These results underscore the need to consider microbiome TIR NADases when evaluating NAD metabolism in the human holobiont.

First Authors:
James S Weagley

Correspondence Authors:
Jeffrey I Gordon

All Authors:
James S Weagley,Mark Zaydman,Siddarth Venkatesh,Yo Sasaki,Neha Damaraju,Alex Yenkin,William Buchser,Dmitry A Rodionov,Andrei Osterman,Tahmeed Ahmed,Michael J Barratt,Aaron DiAntonio,Jeffrey Milbrandt,Jeffrey I Gordon