Abstract
Aims
Circulating lipopolysaccharides (LPSs), associated with both infection and inflammation, may arise from the gastrointestinal tract microbiota, and the levels may be affected by daily nutrition. We investigated whether nutrient intake affects the association of serum LPS activity with prevalent obesity, metabolic syndrome (MetS), diabetes, and coronary heart disease (CHD) and with the risk of incident CHD events.
Methods
The nutrition cohort (n = 2,452, mean age ± SD, 52.2 ± 10.1 years) of the FINRISK 1997 Study was followed up for 10 years. Information on macronutrient intake at baseline was collected from 24-h dietary recall. Serum endotoxin activities were determined by the Limulus amebocyte lysate assay.
Results
LPS activity was associated directly with the total energy intake and indirectly with carbohydrate intake in lean, healthy subjects. High LPS was significantly associated with prevalent obesity, MetS, diabetes, and CHD events, independently of established risk factors, CRP, and total energy or nutrient intake. The ORs (95 % CI) were 1.49 (1.21–1.85, p < 0.001, Q2–4 vs. Q1) for obesity, 2.56 (1.97–3.32, p < 0.001, Q2–4 vs. Q1) for MetS, 1.94 (1.06–3.52, p = 0.031, Q2–4 vs. Q1) for CHD, and 1.01 (1.00–1.01, p = 0.032, LPS unit) for diabetes. In the follow-up, high LPS was significantly associated with the risk of CHD events with a hazard ratio of 1.88 (1.13–3.12, p = 0.013, Q2–4 vs. Q1). This association was independent of baseline established risk factors, diet, obesity, MetS, and diabetes.
Conclusion
A high serum LPS activity is strongly associated with cardiometabolic disorders, which supports the role of bacterial infections and immune response in their etiology.


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Acknowledgments
This work was supported by the grants from the Academy of Finland (1266053 to P.J.P., 136895 and 263836 to S.M.), the Sigrid Juselius Foundation (P.J.P), the Aarne Koskelo Foundation (K.A.E.K), Folkhälsan Institute of Genetics (M.L.), the Finnish Dental Society Apollonia (K.A.E.K), and the Finnish Foundation for Cardiovascular Research (V.S.).
Conflict of interest
Elisa Kallio, Katja Hätönen, Markku Lehto, Veikko Salomaa, Satu Männistö, and Pirkko Pussinen declare that they have no conflict of interest.
Human and animal rights disclosure
All procedures followed were in accordance with the ethical standards of the responsible committee on human experimentation (institutional and national) and with the Helsinki Declaration of 1975.
Informed consent disclosure
Informed consent was obtained from all patients for being included in the study.
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Kallio, K.A.E., Hätönen, K.A., Lehto, M. et al. Endotoxemia, nutrition, and cardiometabolic disorders. Acta Diabetol 52, 395–404 (2015). https://doi.org/10.1007/s00592-014-0662-3
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DOI: https://doi.org/10.1007/s00592-014-0662-3


