Treat the Heart With the Gut

December 30, 2015
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Targeting Gut Microbes to Prevent Heart Disease

Research by physician Stanley Hazen of the Cleveland Clinic and colleagues has shown that certain bacteria in your gut can transform choline (found in meat and eggs) and other dietary nutrients into trimethylamine N-oxide (TMAO), which slows the breakdown of cholesterol.

The higher your TMAO levels become, the more fatty plaques may collect in your arteries, which may promote atherosclerosis and other heart problems.

As The Atlantic recently reported, Dr. Hazen's colleague Zeneng Wang discovered that the chemical 3,3-dimethyl-1-butanol (DMB) prevents gut microbes from turning choline into trimethylamine (TMA), thereby lowering the risk of heart problems.^1,²

DMB is a choline-like compound that works by "gumming up" the enzymes required by the bacteria to digest choline, which stops TMA production. According to The Atlantic:³

"It takes two to TMAO: Bacteria first transform choline into TMA, before an enzyme from the host animal changes TMA into TMAO. At first, Hazen's team tried to prevent the second part of this chain by blocking the animal enzyme.

They succeeded, lowering TMAO levels in mice and making them resistant to atherosclerosis. But there was just one problem: disabling the enzyme leads to a build-up of TMA, which doesn't harm the heart but does smell of rotting fish."

By targeting gut microbes with DMB, the mice, which were bred to be vulnerable to atherosclerosis, produced less TMAO even when fed a choline-rich diet. They also had fewer signs of the condition. As written in Cell:⁴

"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."

Your Gut Microbes Might Be One Reason Why Eating Red Meat Is Linked to Heart Disease

Your gut bacteria can also metabolize L-carnitine, a substance found in red meat, eggs, and other foods, and in so doing produce TMAO.

Interestingly, people with diets high in L-carnitine, i.e. meat eaters, had a gut microbe composition that was more prone to forming TMAO, while vegetarians and vegans did not.

Even after consuming large amounts of L-carnitine in a steak or supplement, the vegetarians and vegans in the study did not produce significant amounts of TMAO.

Does this mean that you should avoid meat and L-carnitine?

I believe the answer is a resounding no. The science is very clear that L-carnitine is required to shuttle fatty acids into the mitochondria to burn them as fuel. It is an important mitochondrial nutrient and I personally take a supplement because I don't eat much red meat.

However I believe healthy non-CAFO red meat can be an important part of a healthy diet. One just does not want to consume it in excess that almost everyone does. Anything over 3-4 ounces. and 2 ounces for people under140 pounds, is far too much protein and will raise mTOR levels.

If you are a vegetarian, or someone that has a mitochondrial dysfunction disease then I strongly believe that you should be on a supplement of L-carnitine, not acetylcarnitine, simple plain L-carnitine.

However, Dr. Hazen and colleagues believe that eating red meat alters your gut flora in a way that predisposes your body toward TMAO production, and subsequently, heart disease.⁵

I suspect this research is flawed as they never really carefully examined the quantity or quality of meat being consumed. CAFO meat should be avoided for reasons previously discussed and excessive meat consumption,

In my view, excessive meat, especially CAFO meat, will not only contribute to heart disease, but cancer, obesity, diabetes and neurodegenerative diseases.

U.S Military Using Gut Microbes to Stave Off Disease and More

Rice University synthetic biologist Jeff Tabor received a three-year grant from the U.S. Office of Naval Research (ONR) to research how gut microbes may be used to support health on the battlefront.

Synthetic biology involves genetically engineering microorganisms, making it highly controversial. Tabor's work involves a genetically engineered E. coli cell that is capable of sensing certain chemical disturbances.

The ultimate goal is that the cells would then "fire off a battery of molecules to neutralize [the disturbances]."⁶ The cells would be designed to only survive a matter of hours in your gut, carrying out their intended purpose and then dying off naturally.

To date, his research in mice has been related to obesity and other metabolic issues. When mice were fed the modified E. coli cells, the "sensors" were activated, which means the targeted chemicals were successfully located.

The research is only in the beginning stages, but plans are underway to produce GE cells that would carry up to a dozen sensors and be capable of producing targeted drugs on the spot, including highly-targeted antibiotics that target bacterial chemicals linked to obesity, inflammation, and more.⁷

Manipulating gut bacteria with "synthetic probiotics" might one day be used to treat diabetes, autoimmune disorders, cancer, neurological disorders, obesity, and more.

The U.S. military is hoping that tweaking the microbiome might also help the armed forces stay healthy in the face of extreme conditions, stress, disruptions to circadian rhythm (like living on a submarine), and sleep loss. Scientific American reported:⁸

" … [T]he Navy may find creative ways to deploy these synthetic probiotics not just to avoid obesity and its attendant problems but to quickly shift body weight and metabolism as necessary, Tabor suggests.

'Imagine you have a team of marines going from a temperate environment, say, at sea level, to a really cold environment, like up on top of a mountain, in a short period of time. You want them to be able to put on some fat quickly to be more robust in the cold environment.'

The solution? A dose of yogurt laced with synthetic probiotics that change warfighters' metabolism to increase fat for a couple of weeks — and after that another dose to take it off when they return to sea level."

The Microbiome Is a 'Key Regulator' of Your Brain and Behavior

Your microbiome affects your heart, your weight, and, yes, also your brain and behavior. So-called germ-free mice, which have no microbiome to speak of, have altered behavior and brain function.

In a study by Dr. John Cryan, a neuropharmacologist from the University College Cork in Ireland, mice without microbes in their intestines are unable to recognize other mice around them. Dr. Cryan believes microbes may communicate with the brain and help us be social, which in turn allows the microbes to spread to others.⁹

In addition, mice lacking gut bacteria have been found to engage in "high-risk behavior," and this altered behavior was accompanied by neurochemical changes in the mouse brain.¹⁰ Dr. Cryan believes beneficial microbes could one day be used to treat mental health problems in humans.

He dubbed the compounds "psychobiotics." He told Scientific American, "That dietary treatments could be used as either adjunct or sole therapy for mood disorders is not beyond the realm of possibility."¹¹

In one notable study by Dr. Cryan and colleagues, the probiotic Lactobacillus rhamnosus had a marked effect on GABA levels — an inhibitory neurotransmitter that is significantly involved in regulating many physiological and psychological processes — in certain brain regions and lowered the stress-induced hormone corticosterone, resulting in reduced anxiety- and depression-related behavior.¹²

Further, researchers have discovered that the absence or presence of gut microorganisms during infancy permanently alters gene expression. Through gene profiling, they were able to discern that absence of gut bacteria altered genes and signaling pathways involved in learning, memory, and motor control.

This suggests that gut bacteria are closely tied to early brain development and subsequent behavior. These behavioral changes could be reversed as long as the mice were exposed to normal microorganisms early in life. But, once the germ-free mice had reached adulthood, colonizing them with bacteria did not influence their behavior.¹³ As reported by the National Institutes of Health (NIH) Record:¹⁴

"Cryan has identified several 'critical windows' for gut microbiota development and in which it might be most possible to transform them: early life, adolescence and old age. But, 'on the whole, it's the early-life period that's instrumental for informing the microbiome composition, which informs our immune system and may shape aspects of brain development as well,' he said."

This is one strong argument for having a vaginal birth as opposed to a C-section (if you have the option), as your baby is "seeded" with microbes as it goes through the birth canal. Breastfeeding further encourages a healthy microbiome in early life, and once your baby is ready for soft foods, you can easily provide abundant probiotics in the form of fermented foods.

However, even though early life is a crucial time for developing a healthy microbiome, you can make favorable changes all throughout your life.

How to Nourish Your Microbiome

Your microbiome is vulnerable to your diet and lifestyle and can be harmed by:

Antibiotics, unless absolutely necessary (and when you do take them, make sure to reseed your gut with fermented foods and/or a probiotic supplement)	Conventionally raised meats and other animal products, as CAFO animals are routinely fed low-dose antibiotics, plus genetically engineered grains, which have also been implicated in the destruction of gut flora	Processed foods (as the excessive sugars, along with otherwise "dead" nutrients, feed pathogenic bacteria)
Chlorinated and/or fluoridated water	Antibacterial soap	Agricultural chemicals

In addition to avoiding the harmful aspects above, reseeding your gut with beneficial bacteria is essential for maintaining proper balance and achieving optimal physical and mental health. In light of this, here are my recommendations for optimizing your gut bacteria.

Fermented foods are the best route to optimal gut health, as long as you eat the traditionally made, unpasteurized versions.

Healthy choices include lassi (an Indian yoghurt drink, traditionally enjoyed before dinner), fermented grass-fed organic milk such as kefir, various pickled fermentations of cabbage, turnips, eggplant, cucumbers, onions, squash, and carrots, and natto (fermented soy).

Fermented vegetables, in particular, are an excellent way to supply beneficial bacteria back into your gut. As an added bonus, they can also a great source of vitamin K2 if you ferment your own using the proper starter culture.

We had samples of high-quality, fermented organic vegetables made with our specific starter culture tested, and a typical serving (about two to three ounces) contained not only 10 trillion beneficial bacteria, but it also had 500 mcg of vitamin K2, which we now know is a vital co-nutrient to both vitamin D and calcium.

Most high-quality probiotics supplements will only supply you with a fraction of the beneficial bacteria found in such homemade fermented veggies, so it's your most economical route to optimal gut health as well.

Probiotic supplement. Although I'm not a major proponent of taking many supplements (as I believe the majority of your nutrients need to come from food), probiotics is an exception if you don't eat fermented foods on a regular basis.