01.07.21
A new review published in the journal Nutrients by Asim K. Duttaroy, a professor and group leader of Clinical Nutrition at the Faculty of Medicine in the University of Oslo, highlights a breadth of research which suggests that certain beneficial bacteria in the gut have a plethora of positive benefits to cardiovascular disease (CVD) risk factors.
“Emerging data have demonstrated a strong association between the gut microbiota and the development of cardiovascular disease risk factors such as atherosclerosis, inflammation, obesity, insulin resistance, platelet hyperactivity, and plasma lipid abnormalities,” Duttaroy wrote.”
A large part of the benefit stems from the metabolites sourced from certain gut microbes, he said, such as trimethylamine-N-oxide (TMAO), short-chain fatty acids, and bile acid metabolites (amino acid breakdown products), each of which is positively associated with better CVD outcomes.
These metabolites are also associated with blood platelet activity, lipid disorders, and oxidative stress, leading Duttaroy to believe that the potential benefits which can be achieved by modulating the bacterial content in the gut are well worth investigating from a clinical perspective in the context of heart disease. Hyperactive platelets are of particular concern to Duttaroy as they have a role in hemostasis, thrombosis, and atherosclerosis – evidence suggests that platelet hyperactivity is more prevalent in people with diabetes, smokers, sedentary lifestyles, aging, obesity, certain gut metabolites, and an unhealthy diet.
Atherosclerosis
Duttaroy pointed to a number of clinical trials further substantiating the role that gut dysbiosis could have in the genesis of atherosclerosis. Inflammation could affect the integrity of a gut barrier, and maintaining a gut barrier’s integrity could be preventative toward inflammation in the atherosclerosis process, he said. One strain in particular, Akkermansia muciniphila, appears to exert notable protective effects toward gut barrier function, by increasing tight junction proteins, which are shown to fix intestinal permeability to prevent pro-inflammatory cytokines from permeating the digestive tract.
One study in particular substantiated the cardiovascular risk that gut dysbiosis could pose. Duttaroy pointed to a number of animal studies which show that the varied effects of antibiotics could increase or decrease cardiac event risk in animal models of heart injury.
Further, certain microbes are able to reduce circulating concentrations of TMAO, a compound which is associated with obesity, insulin resistance, renal disease, CVD on the whole, cardiovascular events, and atherosclerotic plaque size. This is because TMAO exacerbates inflammatory reactions of the vascular wall, and modulates cholesterol and sterol metabolism harmfully.
Hypertension
Studies on animal models show clearly that germ-free mice tend to be hypertensive – beyond this, the short-chain fatty acids that some bacteria produce, and their effect on LDL levels and other pathways are important to consider in the development of hypertension.
“Dysbiosis can promote oxidation of LDL to oxLDL,” Duttaroy said. “Thus, gut dysbiosis also contributes to hypertension through vasoconstriction mediated by oxLDL. Higher levels of oxLDL contribute to hypertension by inhibiting nitric oxide synthesis and endothelin-1.”
Platelet Hyperactivity
“Apart from homeostasis, platelets are involved in several cardiovascular processes, including atherosclerosis, immune system, inflammation, interaction with other cells, and cardiac events,” Duttaroy said.
TMAO, a metabolite produced by gut microbiota, has a clear and pronounced effect on the development of atherosclerosis and thrombotic events, Duttaroy said, pointing to in vitro studies which show that hyperactive platelets have a role in producing more reactive oxygen species, and decreasing NO availability. “Platelet hyperactivity plays a causal role in triggering and maintaining the pro-inflammatory and pro-thrombotic state of obesity, creating an environment favorable for atherothrombotic vascular events,” Duttaroy said.
“Sufficient convincing data have emerged on the relationship between gut dysbiosis and CVD,” Duttaroy said. “However, further work is required for the establishment of gut microbiota-targeted therapy for CVD. Since various experimental and clinical data on the mechanisms of gut microbiota mediated-development of CVD are available, there is a strong possibility of finding new approaches to treat or prevent CVD.”
“Emerging data have demonstrated a strong association between the gut microbiota and the development of cardiovascular disease risk factors such as atherosclerosis, inflammation, obesity, insulin resistance, platelet hyperactivity, and plasma lipid abnormalities,” Duttaroy wrote.”
A large part of the benefit stems from the metabolites sourced from certain gut microbes, he said, such as trimethylamine-N-oxide (TMAO), short-chain fatty acids, and bile acid metabolites (amino acid breakdown products), each of which is positively associated with better CVD outcomes.
These metabolites are also associated with blood platelet activity, lipid disorders, and oxidative stress, leading Duttaroy to believe that the potential benefits which can be achieved by modulating the bacterial content in the gut are well worth investigating from a clinical perspective in the context of heart disease. Hyperactive platelets are of particular concern to Duttaroy as they have a role in hemostasis, thrombosis, and atherosclerosis – evidence suggests that platelet hyperactivity is more prevalent in people with diabetes, smokers, sedentary lifestyles, aging, obesity, certain gut metabolites, and an unhealthy diet.
Atherosclerosis
Duttaroy pointed to a number of clinical trials further substantiating the role that gut dysbiosis could have in the genesis of atherosclerosis. Inflammation could affect the integrity of a gut barrier, and maintaining a gut barrier’s integrity could be preventative toward inflammation in the atherosclerosis process, he said. One strain in particular, Akkermansia muciniphila, appears to exert notable protective effects toward gut barrier function, by increasing tight junction proteins, which are shown to fix intestinal permeability to prevent pro-inflammatory cytokines from permeating the digestive tract.
One study in particular substantiated the cardiovascular risk that gut dysbiosis could pose. Duttaroy pointed to a number of animal studies which show that the varied effects of antibiotics could increase or decrease cardiac event risk in animal models of heart injury.
Further, certain microbes are able to reduce circulating concentrations of TMAO, a compound which is associated with obesity, insulin resistance, renal disease, CVD on the whole, cardiovascular events, and atherosclerotic plaque size. This is because TMAO exacerbates inflammatory reactions of the vascular wall, and modulates cholesterol and sterol metabolism harmfully.
Hypertension
Studies on animal models show clearly that germ-free mice tend to be hypertensive – beyond this, the short-chain fatty acids that some bacteria produce, and their effect on LDL levels and other pathways are important to consider in the development of hypertension.
“Dysbiosis can promote oxidation of LDL to oxLDL,” Duttaroy said. “Thus, gut dysbiosis also contributes to hypertension through vasoconstriction mediated by oxLDL. Higher levels of oxLDL contribute to hypertension by inhibiting nitric oxide synthesis and endothelin-1.”
Platelet Hyperactivity
“Apart from homeostasis, platelets are involved in several cardiovascular processes, including atherosclerosis, immune system, inflammation, interaction with other cells, and cardiac events,” Duttaroy said.
TMAO, a metabolite produced by gut microbiota, has a clear and pronounced effect on the development of atherosclerosis and thrombotic events, Duttaroy said, pointing to in vitro studies which show that hyperactive platelets have a role in producing more reactive oxygen species, and decreasing NO availability. “Platelet hyperactivity plays a causal role in triggering and maintaining the pro-inflammatory and pro-thrombotic state of obesity, creating an environment favorable for atherothrombotic vascular events,” Duttaroy said.
“Sufficient convincing data have emerged on the relationship between gut dysbiosis and CVD,” Duttaroy said. “However, further work is required for the establishment of gut microbiota-targeted therapy for CVD. Since various experimental and clinical data on the mechanisms of gut microbiota mediated-development of CVD are available, there is a strong possibility of finding new approaches to treat or prevent CVD.”
