Response to Comment on: Lassenius et al. Bacterial Endotoxin Activity in Human Serum Is Associated With Dyslipidemia, Insulin Resistance, Obesity, and Chronic Inflammation. Diabetes Care 2011;34:1809–1815

We thank Koduru et al. (1) for highlighting their findings regarding the effects of diet composition on endotoxemia and inflammation. Based on their results, it is evident that dietary factors may modulate the state of endotoxemia in humans. We, however, believe that the issue ismuchmore complex. Pathogenassociated microbial compounds may arise from various sources: diet, bacterial infections, and commensalmicrobiota. Different dietary food products contain various amounts of microbial compounds, the biological activity of which might be modulated by nutrient composition and food processing. Dietary fat especially seems to play a significant role in the absorption process of dietand gut-derived bacterial endotoxins (2). Recent findings emphasize that more attention should be paid to the host microbiota. Evidently, lifestyle, dietary habits, and the use of antimicrobial agents may affect the variety of bacterial species and the microbial load, modulating the composition of commensal microbiota. Overgrowth of gram-negative bacteria in the oral microbiota has been associated with increased endotoxin levels and systemic inflammation. In support of this, we have observed that endotoxin activities in the saliva may vary more than 50-fold among periodontally and systemically healthy individuals (M.L.andP.J.P.,unpublished observations). Average saliva excretion equals 1.0–1.5 L per 24 h, which means that substantial amounts of bacterial endotoxins are swallowed on a daily basis. Notably, simple mastification or mechanical dental procedures, e.g., toothbrushing, may also induce bacteremia and endotoxemia (3). Inflammatory conditions of the periodontium may also increase its permeability to microbial compounds. According to the national Health-2000 survey conducted among adult Finns, the prevalence of gingivitis, deepened periodontal pockets ($4 mm), and more severe forms of periodontal diseases was 74, 64, and 21%, respectively (4). We have recently shown that a high antibody response to periodontal pathogens and endotoxemia in combination with low HDL cholesterol concentration increase the risk of incident cardiovascular disease events (5).On the basis of the above observations, we believe that in addition to gut-related bacteria, the gram-negative pathogen burden deriving fromoralmicrobiota may also play a substantial role in the development of metabolic endotoxemia.