[The contribution of the intestinal microbiome to the formation of the general profile of bacterial DNA in the blood of obese children].

UNLABELLED: Obesity is a multifactorial disease. The gut microbiome disturbances play a significant role in the development of obesity, but emerging data point to a blood microbiome and its association with obesity and other pathologies. Bacterial DNA in the blood represents a pathogen-associated molecular pattern capable of activating the immune system and thereby triggering a cascade of inflammatory responses. The question remains open as to where the bacterial DNA originates, which biotopes shape it, and what role the gut microbiome plays in forming the pool of bacterial DNA in blood. The aim of the study was to compare the bacterial DNA profiles of feces and blood in obese children, to establish relationships between bacterial DNA in blood and feces, and with carbohydrate and lipid metabolism parameters.

MATERIAL AND METHODS: This single-center, cross-sectional study included children and adolescents aged 10 to 18 years with varying degrees of alimentary-constitutional obesity (n=79) and without obesity (n=84). The taxonomic profile of bacterial DNA in blood and feces was analyzed using metagenomic sequencing. Bacterial DNA was isolated from blood and stool samples, and the v3-v4 variable region of the 16S rRNA gene was sequenced. To identify the relationship between bacterial DNA in blood and feces and lipid and carbohydrate metabolism parameters [glucose, total cholesterol, high-density lipoprotein and low-density lipoprotein (LDL)], Spearman's correlation coefficients were calculated.

RESULTS: When comparing bacterial DNA from blood and feces, obese children more often isolated DNA from the families Lactobacillaceae (p=0.043), Porphyromonadaceae (p=0.022), Ruminococcaceae (p=0.065) and less often from Prevotellaceae (p=0.028) and Coriobacteriaceae (p=0.085) compared to children and adolescents without obesity. In obese children, the contribution of intestinal taxa (Lachnospiraceae, Ruminococcaceae, Bacteroidaceae) to the formation of the bacterial DNA profile of the blood was significantly reduced, but the contribution of extraintestinal biotopes (skin, soil and water) was more diverse. Positive associations were found between bacterial DNA of fecal Ruminococcaceae taxa and the level of total cholesterol (ρ=0.347, p=0.002) and LDL (ρ=0.313, p=0.005) and of fecal Coriobacteriaceae and these lipid metabolism parameters (ρ=0.304, p=0.007 and ρ=0.317, p=0.005) in obese children. No positive associations were found between fecal and blood taxa and glucose level.

CONCLUSION: In obese and non-obese children and adolescents, the general profile of bacterial blood DNA is formed by both intestinal and extra-intestinal biotopes. However, in obese children, taxa from extra-intestinal biotopes predominate in the formation of the blood microbiome, which is confirmed by analyzing the proximity of the taxonomic composition of bacterial DNA in blood and feces based on beta diversity indices. The relationship of taxa with blood cholesterol and LDL levels can be considered as a target for microbiota modification and thus reducing the risks of metabolic complications in obesity.