Bacterial DNAemia is associated with serum zonulin levels in older subjects

Giorgio Gargari,Paul A Kroon,Simone Guglielmetti,Patrizia Riso,Raul González-Domínguez,Cristian Del Bo’,Mark S Winterbone,Valentina Taverniti,Giacomo Mantegazza,Cristina Andres-Lacueva,Antonio Cherubini,Stefano Bernardi

doi:10.1038/s41598-021-90476-0

Abstract

The increased presence of bacteria in blood is a plausible contributing factor in the development and progression of aging-associated diseases. In this context, we performed the quantification and the taxonomic profiling of the bacterial DNA in blood samples collected from forty-three older subjects enrolled in a nursing home. Quantitative PCR targeting the 16S rRNA gene revealed that all samples contained detectable amounts of bacterial DNA with a concentration that varied considerably between subjects. Correlation analyses revealed that the bacterial DNAemia (expressed as concentration of 16S rRNA gene copies in blood) significantly associated with the serum levels of zonulin, a marker of intestinal permeability. This result was confirmed by the analysis of a second set of blood samples collected from the same subjects. 16S rRNA gene profiling revealed that most of the bacterial DNA detected in blood was ascribable to the phylum Proteobacteria with a predominance of the genus Pseudomonas. Several control samples were also analyzed to assess the influence of contaminant bacterial DNA potentially originating from reagents and materials. The data reported here suggest that para-cellular permeability of epithelial (and, potentially, endothelial) cell layers may play an important role in bacterial migration into the bloodstream. Bacterial DNAemia is likely to impact on several aspects of host physiology and could underpin the development and prognosis of various diseases in older subjects.

Highlights

The increased presence of bacteria in blood is a plausible contributing factor in the development and progression of aging-associated diseases
These results indicate that the older volunteers under study harbored detectable amounts of bacterial DNA in their blood, in a concentration that varied approximately of one order of magnitude among samples
Based on the data reported here and in the context of previous reports of DNAemia in younger adults, the authors conclude that older individuals harbor detectable amounts of bacterial DNA in their blood and that it has a somewhat distinct taxonomic origin

Summary

Introduction

The increased presence of bacteria in blood is a plausible contributing factor in the development and progression of aging-associated diseases. Correlation analyses revealed that the bacterial DNAemia (expressed as concentration of 16S rRNA gene copies in blood) significantly associated with the serum levels of zonulin, a marker of intestinal permeability This result was confirmed by the analysis of a second set of blood samples collected from the same subjects. Bacterial DNA in blood plausibly originates from (1) direct translocation of microbial cells through an injured epithelial barrier, (2) microbe sampling activity of antigen-presenting cells (dendritic cells, macrophages) at the epithelium, or (3) via microfold (M) cells in Peyer’s patches of the intestine[10] These events increase the presence of bacterial factors found systemically (in bloodstreams and organs), resulting in a significant stimulation of the host’s immune system. It supports the hypothesis that intestinal barrier deterioration occurs during aging, promoting increased absorption of luminal factors[18], and supports the more than 100-year-old Metchnikoff speculation that, during aging, “the intestinal microbes or their poisons may reach the system generally and bring harm to it”[19]

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