There is a direct pathway that connects the gut to the heart and brain. A ‘highway’ along which, ‘on board’ bad cholesterol, travels a substance which is present in some bacteria of the microbiota and which can trigger thrombosis responsible for heart attacks and strokes. This was discovered by a group of Italian researchers directed by Francesco Violi, honorary president of Simi (Italian Society of Internal Medicine) and professor emeritus of the Sapienza University of Rome, who will talk about it during the 125th Simi Congress scheduled in Rimini from 11th to October 13th. To counteract the new disease mechanism, targeted therapies are being studied.
“Atherosclerosis – remind the Simi Internists – is a multifactorial disease associated with many risk factors, the best known of which are smoking, type 2 diabetes, obesity, metabolic syndrome, hypertension and ‘increase in bad LDL cholesterol’. Violi’s team has identified a new person responsible for the pathology.
What is lipopolysaccharide (Lps) and what does it do?
“The ‘culprit’ on which our attention has focused – explains the specialist – is the lipopolysaccharide (Lps), a glycolipid found in the wall of Gram-negative bacteria such as Escherichia coli. This substance enters the circulation after crossing the wall of the intestine and is located in the wall of the arteries, where causes chronic low-grade inflammation. This damages the arteries over time and draws platelets from the bloodstream which cause thrombosis of the affected vessel. We have already conducted experiments on animals – reports Violi – which have demonstrated how LPS actually has this thrombotic ‘vocation'”. Here is therefore “a new route through which atherosclerotic damage, thrombosis, manifests itselfand it is a discovery of Italian research. Now it is necessary to understand how to block this mechanism, to prevent heart attacks and other forms of arterial obstruction caused by LPS.”
“The ‘primum movens’ of this new disease mechanism – the internal medicine specialists summarize – it is an altered permeability of the intestine caused by dysbiosis, i.e. an alteration of the intestinal microbiotawhich favors the passage of lipopolysaccharide into the general circulation; this induces an inflammatory state at the level of the arterial wall, which kicks off the progression of atherosclerosis involving not only the lining cells of the arteries (endothelial cells), but also the white blood cells and platelets, making them more prone to forming thrombi” .
Lps “moves in the bloodstream on board LDL cholesterol – specifies Violi – which it uses as a ‘Trojan horse’ to penetrate the wall of the arteries. The ability of cholesterol to inflame the arteries could therefore be due not to it directly, but to Lps which stimulates the production of free oxygen radicals, oxidants which inflame the artery wall and damage it. This damage then attracts platelets which form a thrombus, interrupting the flow of blood within that artery and thus giving rise to a heart attack or stroke.”
Who is most at risk?
“The presence of these dangerous bacteria that can send LPS into circulation – continues the expert – is more likely in subjects classically at risk of heart attack, for example people with diabetes or obesity. Dysmetabolic individuals present chronic low-grade intestinal inflammation which is associated with intestinal dysbiosis with a prevalence of pathogenic bacteria such as E. coli. We carried out experiments on obese animals and” in fact “we managed to demonstrate that this condition is associated with intestinal dysbiosis, an increase in Lps and an increased risk of thrombosis”. Comments the president of Simi, Giorgio Sesti: “This important series of research conducted by a group of Italian researchers affiliated with our scientific society are the demonstration that only the internal medicine doctor is capable of having a holistic clinical and experimental approach capable of tackling the study of complex and multifactorial pathologies that require medical knowledge transversal to many specialist areas”.
But how can we intervene to combat the effects of the discovered mechanism?
“For now – replies Violi – we can only make hypotheses. There are various possibilities for preventing damage from LPS that we are exploring. One could be modulate the composition of the intestinal bacterial flora, through the administration of probiotics and prebiotics. Another possibility is to administer cycles of non-absorbable intestinal antibiotics to correct dysbiosis: in animals we have obtained very interesting results. Yet another way could be to block the action of Lps once it has entered the circulation, preventing it from interacting with its receptor on the wall of the arteries, therefore activating the entire cascade of events that will lead to thrombosis: we are already working on one possible pharmacological therapy that exploits Lps as a new anti-thrombosis therapeutic target. Finally, we could also think of a possible favorable action of Glp-1 receptor analogues”: another application of the new anti-diabetes and anti-obesity drugs, “since they reduce intestinal permeability and have a cardiovascular protective effect. But there is no evidence to that effect,” at least at the moment.
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