A fat‐enriched diet modifies intestinal microbiota and initiates a low‐grade inflammation, insulin resistance and type‐2 diabetes. Here, we demonstrate that before the onset of diabetes, after only one week of a high‐fat diet (HFD), live commensal intestinal bacteria are present in large numbers in the adipose tissue and the blood where they can induce inflammation. This translocation is prevented in mice lacking the microbial pattern recognition receptors Nod1 or CD14, but overtly increased in Myd88 knockout and ob/ob mouse. This ‘metabolic bacteremia’ is characterized by an increased co‐localization with dendritic cells from the intestinal lamina propria and by an augmented intestinal mucosal adherence of non‐pathogenic Escherichia coli. The bacterial translocation process from intestine towards tissue can be reversed by six weeks of treatment with the probiotic strain Bifidobacterium animalis subsp. lactis 420, which improves the animals9 overall inflammatory and metabolic status. Altogether, these data demonstrate that the early onset of HFD‐induced hyperglycemia is characterized by an increased bacterial translocation from intestine towards tissues, fuelling a continuous metabolic bacteremia, which could represent new therapeutic targets.

Background: The bridge between food intake and weight is not fully understood. Recently, the role of gut microbiota and bacterial lipopolysacharides (LPS) in weight has been noted. Objective: The objective was to evaluate the relation between plasma LPS concentration and food intake. Design: A dietary survey was conducted in 1015 subjects randomly recruited in France. The participants were given oral and written instructions on how to keep a consecutive 3-d food record. Plasma LPS was measured in a subsample of 201 men. To assess, under controlled conditions, the differential impact of various high-energy diets, plasma LPS concentrations were measured in mice fed a high-fat or a high-carbohydrate diet over a 4-wk period. Results: In humans, no significant relation was observed between cardiovascular disease risk factors, carbohydrate and protein intakes, and plasma LPS concentration. Conversely, positive correlations were observed with fat and energy intakes. In a multivariate analysis, endotoxemia was independently associated with energy intake. Compared with the control mice, mice fed a high-energy diet showed an increase in plasma LPS. However, in mice fed a high-carbohydrate diet, the increase in plasma LPS was blunted compared with mice fed a high-fat diet. Conclusions: In this large sample of healthy men from a population-based sample, we found a link between food intake and plasma LPS. Experimental data suggest that fat was more efficient in transporting bacterial LPS from the gut lumen into the bloodstream. The results of this study add to the knowledge of mechanisms responsible for relations between food intake and metabolic diseases.

To determine the relationships between pulse wave velocity (PWV), an estimate of arterial distensibility and cardiovascular risk factors. This cross-sectional population-based study was carried out from 1995 to 1997 to investigate these relationships. Some 993 subjects, aged 35–64 years (52.7% men), living in the south-west of France, were randomly selected from electoral rolls and participated in a cross-sectional study. Medical examinations were performed by specially trained medical staff. Carotid-femoral PWV was measured using a semi-automatic device (Complior, Garges les Gonesse, France). The relationships between PWV and risk factors were assessed, first in subjects not treated with hypolipidaemic, antidiabetic and antihypertensive drugs and then in treated subjects. In subjects not treated for cardiovascular risk factors, age, gender, systolic blood pressure (SBP) and heart rate ( P < 0.001) were the variables significantly associated with PWV. In treated patients, age ( P < 0.01), SBP ( P < 0.001), heart rate ( P < 0.001), apolipoprotein B ( P < 0.05) and the number of treated cardiovascular risk factors ( P < 0.05) were positively correlated with PWV. This study shows that, in a sample of subjects at high risk, the cumulative influence of risk factors, even treated, is an independent determinant of arterial stiffness. These results suggest that PWV may be used as a relevant tool to assess the influence of cardiovascular risk factors on aortic stiffness in high-risk patients.

We recently described a human blood microbiome and a connection between this microbiome and the onset of diabetes. The aim of the current study was to assess the association between blood microbiota and incident cardiovascular disease. D.E.S.I.R. is a longitudinal study with the primary aim of describing the natural history of the metabolic syndrome and its complications. Participants were evaluated at inclusion and at 3-, 6-, and 9-yearly follow-up visits. The 16S ribosomal DNA bacterial gene sequence, that is common to the vast majority of bacteria (Eubac) and a sequence that mostly represents Proteobacteria (Pbac), were measured in blood collected at baseline from 3936 participants. 73 incident cases of acute cardiovascular events, including 30 myocardial infarctions were recorded. Eubac was positively correlated with Pbac (r = 0.59; P<0.0001). In those destined to have cardiovascular complications, Eubac was lower (0.14±0.26 vs 0.12±0.29 ng/µl; P = 0.02) whereas a non significant increase in Pbac was observed. In multivariate Cox analysis, Eubac was inversely correlated with the onset of cardiovascular complications, (hazards ratio 0.50 95% CI 0.35–0.70) whereas Pbac (1.56, 95%CI 1.12–2.15) was directly correlated. Pbac and Eubac were shown to be independent markers of the risk of cardiovascular disease. This finding is evidence for the new concept of the role played by blood microbiota dysbiosis on atherothrombotic disease. This concept may help to elucidate the relation between bacteria and cardiovascular disease.