Bacterial Alchemy, Red Meat Consumption and the Risk for Heart Disease

It’s been known that eating a lot of red meat is linked to having a higher risk for a heart attack, but now new evidence in animal studies and also in humans, shows that the missing link in our understanding as to why this is so, may possibly reside in an overabundance of certain bacteria found in the guts of regular meat-eaters. Gut-microbes seem to have become the darling of our times when it comes to trying to bridge the gap in our rudimentary understanding between the foods we eat and modern diseases, and the science here still remains a big unknown.

According to research just published today in the science journal Nature Medicine,  understanding why regular meat-eaters have a higher risk of heart disease is a matter of simple alchemy. A lot of previous research has shown that excessive red meat consumption is correlated to a higher risk for heart disease and hardening of the arteries through increased cholesterol deposits. Now this new study conducted in mice shows that certain intestinal microbes convert a nutrient that is found in high amounts in red meat called L-carnitine into a chemical called trimethylamine-N-oxide (TMAO); and TMAO promotes cholesterol deposition in the arterial walls and reduces the effective removal of cholesterol by the body, resulting in a high risk for heart disease. Certain carnivorous or carnitine-craving bacteria seem to grow to large colonies in the guts of meat eaters that provide them with their favorite sustenance, where they convert the nutrient L-carnitine into the cholesterol-increasing compound that is so deleterious for the heart when it is overly abundant. L-carnitine is also found in smaller amounts in other foods, such as dairy products, but red meat is by far the highest source of this amino acid.

Another study looking at vegans and meat-eaters showed that when the former ate a sirloin steak the conversion of L-carnitine into the compound TMAO that can be measured in the blood was much lower compared to regular meat-eaters, where the conversion was found to be high. This seems to provide proof for the theory that there is an association between the abundance of certain gut bacteria that use L-carnitine as a substrate and the conversion into TMAO in regular meat-eaters. “It may be that a regular diet of meat encourages higher levels of L-carnitine-TMAO converting intestinal bacteria that feed on L-carnitine that in turn increase the risk of heart disease,” according to one of the study authors.

In the accompanying news article study author Stanley Hazen, head of cardiovascular medicine at the Cleveland Clinic in Ohio, stated that the findings of the study “should give pause not only to meat lovers, but also to people who take L-carnitine supplements which are heavily marketed to promote weight loss and improve athletic performance”. In a New York Times article published today, he was quoted as saying that although not a vegan and a lover of red meat, he personally would not eat a steak more than once every 2 weeks and no more than 4 to 6 ounces at a time. His previous red meat consumption was much higher.


New Research on Link Between Gut Microbes & Weight Loss

Here’s an article in today’s NY Times on new research on the implications of changes in gut microbes leading to weight loss following gastric bypass surgery. It seems like a never-ending stream of research is emerging on this topic. Perhaps fecal transplants will be implicated as treatment in weight-loss protocols in the obese  in the future?

Gut microbes, sex hormones and chronic inflammatory autoimmune disorders

New research published in the journal Science links emergence of sex-hormone driven autoimmune disorders to certain gut microbiota and may offer clues as to why some chronic illnesses with presumed autoimmune etiology, such as MS and rheumatoid arthritis, may be more common in women than men.

Since starting this blog journal with my first entry last year (see archives for blog entry in May and link to original article in German published in DIE WELT http://www.welt.de/print/die_welt/wissen/article106369682/Darmbakterien-machen-dick.html ) describing the association between obesity and the ecology of the human gut microbiome, a lot of solid research has emerged in this area, with mainstream media finally starting to pay increased attention to a topic that used to be subject to ridicule, and was long neglected by the scientific community and mainstream medical community at large: the vital importance of intestinal sanitation. Re-establishing a healthy intestinal flora has been more or less scorned by our modern culture, and relegated as quackery unworthy of serious scientific inquiry as portrayed in T. C. Boyle’s novel ‘Road to Wellville’ that describes the historical fictionalization of corn flakes inventor John Harvey Kellog, whose breakfast cereal business is inspired by a sojourn in a sanitorium in Michigan – an American take on Thomas Mann’s epic novel “The Zauberberg” where the tuberculosis-ridden intellectual elite whiles away in the Swiss Alps in an attempt to cure themselves with a regimen of fresh air at the beginning of the last century. Both fictional accounts satirize holistic naturopathic cures replete with the ‘taking of fresh air’ to aerate pathogen-riddled lungs, or, in the event of the former account, colonic enemas to irrigate the bowels—both rather primitive attempts at restoring health.

Somehow it feels as though the Zeitgeist has changed and we’ve entered a new cycle. It seems as though we’re collectively paying increased attention to our health again, with more of a focus on essentially natural healing methods, especially when modern medicine finds itself at wit’s end. One needs only look at the evolution of treatment-resistant microbes with antibiotics increasingly rendered useless, when they were once considered the magic bullet to curing infections. The history of medicine has seen such a renaissance going ‘back to nature’ before with Samuel Hahnemann’s homeopathic response to curing disease with low potency dilutions of substances based on what was found in the animal, mineral and vegetable kingdom and applied according to the Law’s of Nature and the principals of Similars. Dr. Hahnemann was not a friend of the contemporary medicine practiced during his times.

When the New England Journal of Medicine published findings this past week (http://www.nejm.org/doi/full/10.1056/NEJMoa1205037) of the efficacy of a fecal transplant to cure antibiotic-resistant strains of Clostridium difficile, even the New York Times picked up on it and ran a front-page story in its Global edition – the IHT. (http://www.nytimes.com/2013/01/17/health/disgusting-maybe-but-treatment-works-study-finds.html?ref=science)

When we take antibiotics we unselectively destroy and wipe out gut microbes required for a healthy gut ecology, which may result in the emergence of resistant strains to the detriment of good bacteria. This understanding is by no means new, and yet too many doctors still prescribe antibiotics without thinking twice. And so we live in an era where fecal transplants suddenly become all the rage! Another person’s healthy gut microbes become a sick person’s boon. And it works as a cure when antibiotics fail to do the trick.

Gut microbes are suddenly in. And the link to many diseases originating through an imbalance – or dysbiosis – of the billions of different strains of bacteria our human intestines harbor, is undisputable. (In fact we harbor more bacteria in our human guts than cells in our bodies, to put that into a tangible dimension). The latest research performed in mice that are often used as an animal model to study type 1 diabetes (just published in the journal Science)suggests that there is an association between the emergence of autoimmune disorders and the ecology of gut microbes that are dependent on the presence or absence of testosterone in the host.  This hints at a possible sex-hormone dependent vulnerability to emergence of disease in which specific gut microbes are the pre-requisite. According to this study in mice, testosterone may confer a protection, while female animals develop disease when they harbor certain types of bacteria in their intestines.

Multiple sclerosis and rheumatoid arthritis are just two diseases for which modern medicine still has no explanation as to its precise etiology that are presumed to have some sort of a sex-linked and gut microbial origin with an inflammatory and autoimmune component like type 1 diabetes.

Another recently published study (http://www.sciencedaily.com/releases/2013/01/130118064731.htm) demonstrated how good bacteria in the gut may play an important role in preventing diabetes. When the balance is distorted, inflammation occurs and the disease develops. And even eczema in children can be traced back to these children having a more diverse set of bacteria in their guts normally associated with adults (showing clusters of so-called Clostridium clusters) according to recent findings released in the open access journal BMC Microbiology (http://www.biomedcentral.com/1471-2180/13/12/abstract).

As a physician working in coaching people in disease prevention, I am convinced that nutrition plays one of the most vital, if not the primary role in the prevention of many chronic inflammatory illnesses. It is our primary medicine and I think the scientific link can be found in the maintenance of sanitary intestinal health with an optimal balance of the friendly microbes–in-residence.

With research into the human and also microbial genome advancing at a rapid pace, I believe the medicine of the future will be a combination of a healthy diet of whole, unprocessed foods along with lifestyle changes that are adapted to personal genetic predispositions that the field of metabolomics will help shed more light just a few years down the road. We all have a different enzymatic make up, but with a common sense approach, most chronic diseases should be almost entirely preventable. It will be more important than ever to be wise about our lifestyle choice, especially with the increase in environmental toxins – just think of the toxic metals such a mercury already poisoning our food chains – and to choose our nutrition and lifestyles wisely, where at all possible.

Stay tuned to ‘the mdjournal’ blog for more science emerging in this field of intestinal health and gut microbial genomics.

~ KMD

 

New evidence on link between gut microbes and development of obesity – does overgrowth of endotoxin-producing enterobacteria play a role? New research from China seems to be suggesting this.

Earlier in May this year I posted the English translation of a German article I had written in the  newspaper “DIe WELT” about the link between gut microbes and obesity and the enormous public health implications this knowledge has, if we improve our understanding on the association between the composition of the trillions of bacteria residing in our guts and the development of disease states such as inflammation and obesity.

Here is the link to the older post on the blog for context:

https://themdjournal.wordpress.com/2012/05/31/gutmicrobiota-play-a-pivotal-role-in-the-development-of-obesity/

And here is a new study from China published in the science journal Nature that suggests that overgrowth of endotoxin-producing enterobacteria may lead to obesity via increased inflammation and insulin resistance. Read the open access study here: http://www.nature.com/ismej/journal/vaop/ncurrent/pdf/ismej2012153a.pdf

The complexity of the association between our gut microbial ecology and specific diseases is not to be underestimated. Most research in this area is coming up with very conflicting results when analyzing the precise gut composition and determining the ratios of different microbes residing in the gut by using metagenomic testing of stool samples. A lot more research will be coming out in this area soon, as drug companies and food industry have a very vested interest in promoting pre-biotics and pro-biotics to enhance growth of one bacteria over another.  This study in China looked at a diet of whole grains and traditional chinese medicine and the impact on bacterial growth. More qualitative information on whole foods and outcome on bacterial gut ecology and the link to disease is warranted before single substitutions with both pre- and pro-biotics are to be widely recommended to public at large, in my opinion.

themdjournal

In the United States the public in California voted no to a proposition that genetically modified foods should be labeled as such. In Europe GMO crops are still not permitted.

Here’s my take on the issue:

Proposition 37 failed to win majority of votes in California yesterday for the Nov. 6th election. This was perhaps on the grounds of the proposition itself being poorly put together. The American Academy of the Advancement of Science endorsed the “No to Proposition 37” campaign on the grounds of lacking scientific evidence that GMO crops causes harm. However, that isn’t the point. Consumers should have a right to know what is in their food. Too bad about the weak study and lacking scientific evidence that caused much media hype coming out of France last month. It entirely back-fired and served Monsanto well and put the entire debate on weaker ground. But there seems to…

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California Rejects Labeling of Genetically Modified Food (GMO) in Nov. 6 Election

In the United States the public in California voted no to a proposition that genetically modified foods should be labeled as such. In Europe GMO crops are still not permitted.

Here’s my take on the issue:

Proposition 37 failed to win majority of votes in California yesterday for the Nov. 6th election. This was perhaps on the grounds of the proposition itself being poorly put together. The American Academy of the Advancement of Science endorsed the “No to Proposition 37” campaign on the grounds of lacking scientific evidence that GMO crops causes harm. However, that isn’t the point. Consumers should have a right to know what is in their food. Too bad about the weak study and lacking scientific evidence that caused much media hype coming out of France last month. It entirely back-fired and served Monsanto well and put the entire debate on weaker ground. But there seems to be universal agreement that scientifically, no conclusive evidence has shown that GMO crops cause harm to human health. It’s just going to remain a personal issue what one believes, but my gut instinct tells me that genetically altering crops and proteins that we ingest on a daily basis is going to have unprecedented and unknown long-term health sequelae that we cannot even fathom today based on the science that takes years to emerge. Just like some grains that have mutated over the centuries of human existence are known to cause autoimmune diseases in some people lacking the enzymes to assimilate them, these GMO crops are likely changing the inherent natural state of certain foods way faster than our human guts and bacteria may be able to evolve to process and recognize them. At least based on theory. Whether GMO crops are harmless or harmful to human health will remain a personal opinion without the scientific evidence. But it should remain a choice whether one wants to eat processed foods with genetically altered ingredients or not. And this proposition would have allowed consumers to make precisely those personalized choices when shopping for foods. A better, more cogent proposition for clearer labeling should be drafted that will avoid confusion among consumers already confused about food choices. Foods labeled as organic in the U.S. cannot be GMO, so that is already a smart way for consumers concerned for their health to make their choices.

~ KMD

And here is a link to a NPR (national public radio) report on this today:

http://www.npr.org/blogs/thesalt/2012/11/07/164595923/california-rejects-genetically-modified-food-labels-supporters-vow-to-fight-on?live=1%3Futm_source%3DNPR&utm_medium=facebook&utm_campaign=20121107

New research on gut microbiota and dietary influences

New research emerges on benefit of a paleolithic diet and its influence on gut microbiota ! The role of gut microbiota is becoming an increasing focus of research as it is understood to be intricately linked to many modern diseases.

A healthy diet may have more impact than drugs in treating obesity and other chronic illnesses linked to a poor Western diet rich in refined carbohydrates, sugars and an overconsumption of red meats and dairy products.

A paleolithic diet rich in raw foods such as vegetables and fruit may exert its influence through the interplay with microbes residing in the human gut.

See abstract of new research published in the U.S. library of Medicine, PubMed:

http://www.ncbi.nlm.nih.gov/pubmed/22989504.

Gutmicrobiota play a pivotal role in energy balance and contribute to development of obesity. A scientific microcosm with broad public health implications.

Darmbakterien und Adipositas / GUT MICROBES and Obesity => read the following article in German as it appeared in print in the daily newspaper “DIE WELT”.

Here is an approximate translation into English:

Gut Microbiome, Nutrition, and the Link with Obesity and Cancer

 

by Karen Dente-Mouradian, M.D.

In medicine today one refers to the totality of the intestinal microbes as the microbiome, as opposed to the intestinal flora, which alludes more to the plant world. The living microbiome consists of the entirety of the microbiological bacterial community: there is a tremendous diversity of species, with trillions of different intestinal bacteria thought to be colonizing the human gut. This is ten times the number of the cells contained in the human body. On the genetic level, this translates to a scale of about 100 times more microbial genes in the intestine alone, than are found in all human cells. Many of these genes play a crucial role in energy metabolism. Gut microbes also are thought to have an important effect on immune regulation, the prevention of malignant tumors as well as the preservation of colonic mucosa cells.

Nine of 70 bacterial strains have been defined that are known to live in the human intestine. So-called Firmicutes and Bacteroidetes are the two most common groups of bacteria defined in the human gut. These bacteria, present mostly in the colon, use special enzymes that digest fermentable fibers that man alone is unable to digest,  and assist in breaking these nutritents down into usable energy substrates. Fermentable fibers are often found in foods such as oat bran or beetroot. Whether these bacteria benefit themselves and live in symbiotic mutualism with us human hosts, or are rather to be regarded as neutral commensalists that do not draw any benefit for themselves is subject to debate among biological ecologists.

Analyzing the composition of the human microbiome along with the impact on pathological development is currently beginning to draw some renewed interest as a major focus of research in microbiology, especially given the the growing tide of the obesity epidemic worldwide,  in conjunction, also, with the understanding of antibiotics’ bacteria-eradicating effects on the intestinal flora. Of course the food industry has its self-interested role in supporting the capitalization of food products containing so-called pre-biotics and probiotics that seek to supplement foods with either fermentable fibers (pre-biotics) that stimulate gut microbes already present or as a source of supplemental live bacteria that can colonize the gut (probiotics). And smaller as well as large global corporations have a very vested interest in promoting researchers and their research in this area.

“Determining the exact composition of the microflora, and finding an association with either healthy or overweight people is currently a very hot research topic,” said Walter Gall, director of clinical study Metabolon Inc., USA. The biotech company based in North Carolina intends to market diagnostic tests that will detect early metabolic changes seen in individuals with pre-diabetic conditions – even before the onset of typical type-2-diabetes, and its associated insulin resistance.

The picture of the composition of the intestinal flora has changed dramatically since the introduction of molecular techniques. The difficulty in the study of bacterial microbiome has always been the lack of culturability of gut microbes. More than 50 percent of the human gut bacteria cannot be grown to the size of countable colonies in any culture medium  – and thus can’t be directly determined. Today, with the advent of genetic analyses using so-called polymerase chain reaction (PCR) techniques, this has changed. However, these genetic tests serve to confirm tests using basic colony culture determined from stool samples collected from the study subjects.

Studies in this area are not yet performed on a sufficient scale to give a definitive indication of the composition of various strains of bacteria in obese persons. The journal “Nature” published a key study on this a few years ago, and concluded that overweight people have a reduced biodiversity in the composition of their gut microbes. Above all, the proportion of so-called Bacteroidetes compared to the Firmicutes groups seen to be increased.

But this “Nature” journal study result stood in contrast to the results of other studies, that found an inverse relationship between the two groups of bacteria to one another.  A recent study of 26 obese and 27 non-obese children, whose results were recently presented at the 19th European Congress on Obesity in Lyon, France, and suggested an influence of diet composition on the distribution pattern of intestinal bacterial species in obese and lean children.  Obese childern were found to have more Firmicutes bacteria compared to Bacteroidetes bacteria. This was found to be linked to a deficiency of protein intake in the diet, with no statistically significant link found with carbohydrates. Liene Bervoets, PhD, who has researched on the subject at the University of Antwerp and presented her research findings, said: “It is interesting to observe that the gut microbiota appear to play a role in the development of obesity in children; when comparing obese and lean children, we can observe very significant differences.”

The mutual influence of intestinal flora and body weight is best understood in the context of energy absorption. It is believed that the microbiome contributes to the long-term positive energy balance in humans. An animal experiment in which the gut flora of obese mice was transplanted in microbe-free mice was able to confirm this. The study looked at mice that gained weight despite a reduced food intake, which suggests it to be more likely for there to be a central role played by the microbiome in weight regulation, regardless of the actual composition of the diet. But this causality has yet to be confirmed in larger studies in humans.

Diet to seem to play a crucial role in the interplay between microbes and excessive fat deposition in individuals receiving poor nutrition. Nutritionists largely agree, for example, that easily fermentable fiber-rich foods such as oat bran and pectin-containing foods such as beetroot, also found in various types of fruit, can exert a preventive effect on the process of fat accumulation in the body. The above-mentioned nutrients cannot be decomposed in the first section of the human intestine. The first segment of the human gut is reponsible, rather,  for the absorption of simple carbohydrates. Nutrients that eventually end up in the large intestine are usually those that will be broken down in a segment of the gut where there are more microorganisms such as the Firmicutes bacteria, which contain the crucial fermenting enzymes to draw energy out of these fibers. These bacteria metabolize the nutrients and generate more energy in the form of short-chain fatty acids. Resulting metabolic intermediates such as butyric acid  are especially important in the colon for the preservation of life the intestinal cell walls. But a build-up of these substrates in the blood is currently also being discussed as an indication of pre-diabetes. In the colon, however, these butyrates are thought to help to prevent the development of colon cancer. They continue to play a role in secreting certain satiety hormones, and act as a natural satiety signal to the brain.

In 2003 the World Health Organization had announced that a diet rich in fiber is the best and only proven effective strategy to prevent obesity, and metabolic diseases such as type-2 diabetes. The sugar molecules found in low glycemic index fiber-rich nutrients are absorbed in the later part of the intestinal tract so that blood sugar levels rise more slowly. An oversupply of sugar damages the body especially when sugar circulates at high spikes and levels in the blood and is failed to be incorporated inside the cells – as is seen in the onset of insulin resistance in type 2 diabetes. The damage is often insidious and can affect the tiniest of blood vessels in many organs, including kidneys, eyes, and the entire circulatory system including the coronary vessels of the heart.

The interplay between nutrients and bacteria is complex, and will require further larger studies to help establish a strong, valid theory of the gut microbiome’s exact role in energy extraction and its contribution to obesity and diabetes, in relation to diet. How specific gut bacteria precisely contribute to the development of diseases such as obesity, diabetes and cancer, remains nebulous, or anybody’s best guess, but the current thinking in the research community interested in nutrition, environmental microbial ecology as it relates to human health is that these trillions of gut microbes play an important and central role in the development of these  non-communicable diseases that the W.H.O. has set a goal of combatting in the coming decade in developing and non-developing nations worldwide.