2 Hydroxybutyric Acid-Producing Bacteria in Gut Microbiome and Fusobacterium nucleatum Regulates 2 Hydroxybutyric Acid Level In Vivo

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.

The Role of Mass Spectrometry in Hepatocellular Carcinoma Biomarker Discovery

“…Of particular note, the altered levels of trimethylamine-N-oxide (TMAO) and 2-hydroxybutyric acid display high consistency in the alteration in blood samples. TMAO has previously been correlated with microbial dysbiosis [57,58], while 2-hydroxybutyric acid has been linked to both energy metabolism [59] and the gut microbiome [60]. Considering that bile acids also interact with the gut microbiota, this illustrates the potential role of the gut microbiota in the pathophysiology of HCC.…”