Potential Influence of Tryptophan Metabolites on Translocation of Bacterial DNA into the Blood in Normal Conditions and in Various Obesity Phenotypes

Abstract

It is known that obesity changes the permeability of the intestinal wall, including for bacterial DNA. Therefore, obese patients differ from healthy individuals both in the content of bacterial DNA in the blood and in microbiotic metabolites. Indole metabolites are specific products of tryptophan conversion by intestinal microbiota. Some indoles are involved in the regulation of tight junction protein expression and are, thus, important for the regulation of intestinal permeability. The aim of our study was to investigate the relationship between the content of tryptophan metabolites in feces and the level of bacterial DNA in the blood. Materials and methods. The study included healthy donors without obesity (n = 138) and patients with obesity (n = 128) who were divided into subgroups with MHO (metabolically healthy obesity) and MUHO (metabolically unhealthy obesity). Bacterial DNA was isolated from venous blood samples, and metagenomic sequencing of the v3–v4 variable region of the 16S rRNA gene was performed. Both the frequency of isolation of individual taxa from samples and the share of these taxa in the total pool of bacterial DNA in the blood were compared. Concentrations of tryptophan metabolites in fecal extracts were determined by high-performance liquid chromatography with mass spectrometry. Chromatographic separation was performed using a Discovery PFP HS analytical column; a mass spectrometric detector based on an Agilent 6470 MRM triple quadrupole and electrospray ionization was used for detection. Results. Similar decreases in the content of metabolites of the kynurenine and indole pathways of tryptophan catabolism are noted in the intestines of patients with MHO and MUHO. In obesity, there is an increase in DNA translocation of the genera Rhodococcus, Streptomyces, CF231, Leuconostoc, Burkholderia, Providencia, and Enhydrobacter. Higher blood DNA content of Flavobacterium, Phascolarctobacterium, Kaistobacter, Comamonas, and Enhydrobacter was a feature of patients with MHO. In MUHO, translocation of Prevotella, Blautia, Coprococcus, Ruminococcus, Paracoccus, and Pseudomonas DNA into the blood was increased. In patients with MHO, a positive effect of intestinal kynurenine on the diversity of bacterial DNA in the blood was observed, whereas the concentration of 5-hydroxyindole-3-acetate in feces in MUHO was negatively associated with the diversity characteristics. Conclusions. The content of tryptophan metabolites in feces correlates with the presence of DNA of various taxa in the blood both negatively and positively, which indicates their role in regulating bacterial DNA translocation from the intestine.