Biomarkers of lipopolysaccharide-associated phenotypes in gout patients

Gout is a chronic metabolic disease that occupies a significant place among chronic diseases worldwide. In 2020, 55.8 million people worldwide suffered from gout, corresponding to 0.7% of all mankind, and the prevalence continues to increase annually. Given the increasing incidence of gout, more personalized approaches to the treatment of patients with gout need to be developed. This study aimed to identify various subgroups (phenotypes) of gout patients and describe their characteristics based on a comprehensive analysis of plasma immunological and metabolic biomarkers.

Three phenotypes were identified using cluster analysis:

• The "permeable intestine" phenotype is characterized by the highest levels of lipopolysaccharide-binding protein (LBP) — 26.1 [22.6; 30.7] ng/ml and zonulin — 74.7 [58.9; 120.1] ng/ml, as well as a high BMI — 31.38 [30.64; 35.06] kg/m2 and elevated levels of TGF-B — 6.32 [3.33; 30.5] ng/ml.
• The phenotype is "metabolic", which is characterized by the highest BMI — 39.79 [35.99; 40.89] kg/m2, as well as the highest levels of nitric oxide synthase 3 (NOS-3) — 6,6 [3,1; 8,5] ng/ml and BPI — 298 [249; 367.2] pg/ml.
• The phenotype with "hyporesponders on LPS", demonstrating the low levels of most inflammatory and metabolic markers: LBP — 11.65 [10.27; 14.72] ng/ml, zonulin — 34.1 [23.8; 43.4] ng/ml, NOS-3–0 [0; 2.35] ng/ml, BPI — 64.6 [43.4; 87.7] pg/ml and the low BMI was 29.15 [27.9; 29.4] kg/m2.

The data obtained suggest new targets for therapeutic effects, for example, by influencing the manifestations of endotoxinemia in gout, LPS-binding systems, and LPS itself.

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