Blood Microbiota Dysbiosis Is Associated with the Onset of Cardiovascular Events in a Large General Population: The D.E.S.I.R. Study

Abstract

AimWe 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.Methods and ResultsD.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.ConclusionPbac 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.

Microbiotes et maladies métaboliques

“…Le temps de survie des bactéries dans les tissus n'est pas connu. Des fragments d'ADN bactériens sont égale-ment retrouvés dans les organes et le sang chez la souris comme chez l'homme [57][58][59]. Certaines de ces séquences d'ADN sont prédictives de l'apparition du diabète de type 2 [59] tandis que d'autres sont associées à l'apparition d'événements cardiovasculaires [58].…”

“…Des fragments d'ADN bactériens sont égale-ment retrouvés dans les organes et le sang chez la souris comme chez l'homme [57][58][59]. Certaines de ces séquences d'ADN sont prédictives de l'apparition du diabète de type 2 [59] tandis que d'autres sont associées à l'apparition d'événements cardiovasculaires [58]. Dans les tissus, les bactéries, ou leurs fragments, induisent une stimulation de la prolifération de précurseurs pré-adipocytaires et de macrophages, contribuant ainsi au développement de l'obésité et de l'insulino-résistance.…”

Clinical Implications of Circulating Microbiome in Cardiovascular Disease Patients

“…Gut bacteria were identified in the circulation of ESRD patients and these patients had higher levels of inflammatory markers like high sensitive C-reactive protein (CRP), interleukin-6 and lactate in plasma, indicating that Gut bacteria translocation is associated with micro-inflammation in ESRD patients. In continuation with this, presence of blood microbiota and its long-term prognosis in CVD patients was studied for the first time which concluded that perturbations in blood microbiota equilibrium is associated with or linked with the onset of the disease [6]. Successively, another paper on the presence of circulating microbiome in CVD patients presented similar findings [7].…”

“…The presence of circulating microbiome in cardiac patients was identified for the first time by Amar et al [6]. An increased Proteobacteria population in CVDs correlated with major factors like age, blood pressure, fibrinogen and alanine aminotransferase (ALT) levels.…”

Le microbiote intestinal à l’origine de nouvelles perspectives thérapeutiques pour les maladies métaboliques ?

“…Cela suggère qu'une dysbiose tissulaire pourrait être un facteur contributif important du diabète de type 2 (Figure 2). Il en va de même en ce qui concerne la prédiction des événements cardiovasculaires par la quantification d'autres biomarqueurs d'origine bactérienne dans le sang [25]. Ainsi, une relation de causalité est le récepteur Olfr78 (olfactory receptor 78) des cellules spécialisées du rein [36].…”