There is simple mantra for health.
Maintain Prana and thyself will have healthy living!
Prana = Microbes.
Cleveland Clinic researchers have demonstrated — for the first time — that targeting microbes in the gut may prevent heart disease brought on by nutrients contained in a diet rich in red meat, eggs and high-fat dairy products.
“Many chronic diseases like atherosclerosis, obesity and diabetes are linked to gut microbes,” said Dr. Hazen. “These studies demonstrate the exciting possibility that we can prevent or retard the progression of diet-induced heart diseases starting in the gut. This opens the door in the future for new types of therapies for atherosclerosis, as well as other metabolic diseases.”
TMAO is a gut metabolite formed during the digestion of the nutrients choline, phosphatidylcholine (lecithin) and carnitine, which are abundant in animal products. Blood TMAO levels are associated with heightened risk of heart attacks, stroke and death in clinical studies. Carnitine is abundant in red meat and liver, while choline and lecithin are abundant in beef, lamb, liver, egg yolk and high-fat dairy products.
The present study suggests that targeted inhibition of the first step in TMAO generation, commensal microbial trimethylamine (TMA) production, can help to prevent diet-induced atherosclerosis. The research team inhibited TMA production using 3,3-dimethyl-1-butanol (DMB) in mice fed a high choline or carnitine diet. The mice treated with the inhibitor had less TMAO and developed less atherosclerosis. DMB is not an antibiotic. This important fact suggests that a treatment could target a specific microbial pathway while protecting the gut flora and avoiding antibiotic overuse and resistance, which is a worldwide health crisis.
“We were able to show that ‘drugging the microbiome’ is an effective way to block this type of diet-induced heart disease. The inhibitor prevents formation of a waste product produced by gut microbes, leading to lowering of TMAO levels and prevention of diet-dependent atherosclerosis.” said Dr. Hazen. “This is much like how we use statins to inhibit cholesterol synthesis in human cells.”
Research
Non-lethal Inhibition of Gut Microbial Trimethylamine Production for the Treatment of Atherosclerosis
Highlights
- •Gut microbial trimethylamine lyases are a therapeutic target for atherosclerosis
- •3,3-dimethyl-1-butanol inhibits microbial trimethylamine formation
- •3,3-dimethyl-1-butanol attenuates choline diet-enhanced atherosclerosis
- •Non-lethal gut microbial enzyme inhibition can impact host cardiometabolic phenotypes
Summary
Trimethylamine (TMA) N-oxide (TMAO), a gut-microbiota-dependent metabolite, both enhances atherosclerosis in animal models and is associated with cardiovascular risks in clinical studies. Here, we investigate the impact of targeted inhibition of the first step in TMAO generation, commensal microbial TMA production, on diet-induced atherosclerosis. A structural analog of choline, 3,3-dimethyl-1-butanol (DMB), is shown to non-lethally inhibit TMA formation from cultured microbes, to inhibit distinct microbial TMA lyases, and to both inhibit TMA production from physiologic polymicrobial cultures (e.g., intestinal contents, human feces) and reduce TMAO levels in mice fed a high-choline or L-carnitine diet. DMB inhibited choline diet-enhanced endogenous macrophage foam cell formation and atherosclerotic lesion development in apolipoprotein e−/− mice without alterations in circulating cholesterol levels. The present studies suggest that targeting gut microbial production of TMA specifically and non-lethal microbial inhibitors in general may serve as a potential therapeutic approach for the treatment of cardiometabolic diseases.
The contributory role of gut microbiota in cardiovascular disease
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4215189/
Our group recently discovered that certain dietary nutrients possessing a trimethylamine (TMA) moiety, namely choline/phosphatidylcholine and L-carnitine, participate in the development of atherosclerotic heart disease. A meta-organismal pathway was elucidated involving gut microbiota–dependent formation of TMA and host hepatic flavin monooxygenase 3–dependent (FMO3-dependent) formation of TMA–N-oxide (TMAO), a metabolite shown to be both mechanistically linked to atherosclerosis and whose levels are strongly linked to cardiovascular disease (CVD) risks. Collectively, these studies reveal that nutrient precursors, gut microbiota, and host participants along the meta-organismal pathway elucidated may serve as new targets for the prevention and treatment of CVD.
