Abstract：
2-hydroxybutyric acid (2HB) serves as an important regulatory factor in a variety of diseases. The circulating level of 2HB in serum is significantly higher in multiple diseases, such as cancer and type 2 diabetes (T2D). However, there is currently no systematic study on 2HB-producing bacteria that demonstrates whether gut bacteria contribute to the circulating 2HB pool. To address this question, we used BLASTP to reveal the taxonomic profiling of 2HB-producing bacteria in the human microbiome, which are mainly distributed in the phylum Proteobacteria and Firmicutes. In vitro experiments showed that most gut bacteria (21/32) have at least one path to produce 2HB, which includes Aspartic acid, methionine, threonine, and 2-aminobutyric acid. Particularly, Fusobacterium nucleatum has the strongest ability to synthesize 2HB, which is sufficient to alter colon 2HB concentration in mice. Nevertheless, neither antibiotic (ABX) nor Fusobacterium nucleatum gavage significantly affected mouse serum 2HB levels during the time course of this study. Taken together, our study presents the profiles of 2HB-producing bacteria and demonstrates that gut microbiota was a major contributor to 2HB concentration in the intestinal lumen but a relatively minor contributor to serum 2HB concentration.
摘要：
2-羟基丁酸(2HB)是多种疾病的重要调控因子。在多种疾病中，血清中2HB的循环水平明显升高，例如癌症和2型糖尿病（T2D）。然而,目前没有关于2HB产生细菌的系统研究表明肠道细菌是否有助于循环2HB池。为了解决这个问题，我们使用BLASTP来揭示人类微生物组中产生2HB的细菌的分类学特征，主要分布在变形杆菌门和硬菌门中。体外实验表明，大多数肠道细菌(21/32)至少有一条途径产生2HB，其中包括天冬氨酸，蛋氨酸,苏氨酸,和2-氨基丁酸.特别是,具核梭杆菌合成2HB的能力最强，这足以改变小鼠的结肠2HB浓度。然而，在本研究的时间过程中，抗生素（ABX）和核梭杆菌管饲法均未显着影响小鼠血清2HB水平。一起来看,我们的研究提供了产生2HB的细菌的概况，并表明肠道微生物群是肠腔中2HB浓度的主要贡献者，但对血清2HB浓度的贡献相对较小。
