Genes may affect the level of harmful bacterial toxins in the bloodstream

Lipopolysaccharide, a virulence factor produced by bacteria, is a toxin that can cause a systemic inflammation via the circulation. In a recently completed study, genetic markers were discovered which are associated with a heightened lipopolysaccharide level in the blood.,

Genes may affect the level of harmful bacterial toxins in the bloodstream
Figure 1. Manhattan and QQ plots of genome-wide association study (GWAS) results combined in fixed-effects meta-analysis. We performed a GWAS of endotoxemia, measured by limulus amebocyte lysate assay in 11 296 individuals with Finnish ancestry. The horizontal red line represents genome-wide significance (P

Lipopolysaccharide, a virulence factor produced by bacteria, is a toxin that can cause a systemic inflammation via the circulation. In a recently completed study, genetic markers were discovered which are associated with a heightened lipopolysaccharide level in the blood.

Microbes are part of the human body, and bacteria or their components often end up in the circulation. One such bacterial component is lipopolysaccharide (LPS), which is a toxin. High concentrations of LPS in the cause sepsis. Low LPS levels, known as endotoxemia, cause low-grade . In fact, endotoxemia commonly occurs in connection with, for example, obesity, predicting a heightened risk for both diabetes and cardiovascular diseases.

In a recently completed at the University of Helsinki, LPS levels were measured in the blood of more than 11,000 Finns, after which genome-wide association analyses were carried out to chart the link to the genome. Utilized in further analyses was the FinnGen cohort, which includes genome and disease data on close to 200,000 Finns. The study was carried out collaboratively by the University of Helsinki, the Folkhalsan Research Center, the Finnish Institute for Health and Welfare and the French Institute of Health and Medical Research (INSERM).

“As an entirely new find, we identified an apparent link between the and the amount of bacterial toxins in the blood,” says researcher Jaakko Leskela.

Low-grade inflammation linked to thrombosis

Blood coagulation and defense against infections are interlinked traits, which is in fact beneficial for, for example, the healing of wounds: bleeding must be arrested, while the wound must be protected against infection. In the recently published study, a link between endotoxemia and certain genes associated with was found.

“Our findings connected endotoxemia particularly with , strokes and other diseases related to blood coagulation,” Leskela says.

Consequently, the genes which have such a favorable effect on wound healing also have an unfavorable connection to low-grade inflammation in the body.

“While we do not yet know how exactly these genes associated with coagulation can affect endotoxemia, demonstrating a link is a big step forward as such,” Leskela notes.

The results also indicate that the quality of the human microbiome makes a difference to the risk of developing cardiovascular diseases.

“We have a long road ahead of us in investigating this finding further. However, it is already clear that our results can help to discover new methods for studying and treating low-grade inflammation associated with endotoxemia,” Leskela concludes.


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More information:
Jaakko Leskela et al, Genetic Profile of Endotoxemia Reveals an Association With Thromboembolism and Stroke, Journal of the American Heart Association (2021). DOI: 10.1161/JAHA.121.022482

Journal information:
Journal of the American Heart Association

Provided by
University of Helsinki

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