Did you know that cardiovascular disease is the second leading cause of death in Canada after cancer? In fact, every 7 minutes, in Canada, someone dies from cardiovascular disease, that’s 206 people dying from heart disease every day (1)!
Several factors contribute to cardiovascular disease such as smoking, the amounts of fats and cholesterol in the blood, high blood pressure, the amount of sugar in the blood and blood vessel inflammation (when blood vessels become inflamed, they may become weakened, stretch, and either increase in size or become narrow -- even to the point of closing entirely) (2).
These are all factors that you might have heard previously. But have you heard of the very important link between your gut bacteria and heart disease?
As described in many of our previous blogs, we greatly benefit from microbial activities in our gut. In fact, bacteria in our gut are essential for the production of vitamins (such as vitamin B and vitamin K), digestion of carbohydrates and production of short chain fatty acids among others. Short chain fatty acids are produced when our gut bacteria ferment the fiber we intake and they play an important role in health and disease. Despite these beneficial effects, studies in the past 10 years have shown that the gut microbiota (bacteria harboring our gut) is associated with several diseases such as obesity, type 2 diabetes and cardiovascular disease among others.
As a matter of fact, gut bacteria produce a chemical that increases clotting in the arteries (meaning that it creates a blockage in a blood vessel linked to the heart). Studies show that when this chemical called TMAO (trimethylamine oxide) is added to human platelets, which are tiny blood cells that help your body form clots to stop bleeding, the formation of artery-blocking clots was much faster (4). TMAO is made in the body as a waste product of gut microbes. Furthermore, when researchers increased blood TMAO levels in mice by feeding them a diet rich in choline, which is a TMAO precursor, they found that the animals formed clots faster than those with lower TMAO levels. These results were not seen in mice that lacked gut microbes. When intestinal microbes from mice that produced high levels of TMAO were transplanted into mice with no gut bacteria, the recipients’ clotting risk increased (4). Moreover, TMAO levels were found to be higher in patients with heart failure compared with those without heart failure.
As mentioned above, choline is a precursor of TMAO and this can be found in high amounts in foods rich in cholesterol and fats such as:
Nevertheless, it is still important to take choline nutrients in moderate amount since choline deficiency can cause neurologic impairment. L-carnithine is another common dietary nutrient ingested that produces TMAO (4). In contrast to choline, L-carnithine is not required in our diet since our body is still able to generate it on its own. Studies show that vegetarians and vegans have a reduced capacity to make TMAO compared to omnivores (person that eats food of both plant and animal origin). Basically, this shows that there is a shift in the population of gut bacteria in omnivores that prefer L-carnitine which enhances the potential to produce TMAO (4).
Nutrients rich in L-carnitine are:
Interestingly, the Dr. Oz show recommended a few years ago to take supplements of L-carnitine claiming that it could increase energy, speed up weight loss and improve athletic performance. After seeing the new research about L-carnitine, he is saying to NOT take these supplements as it has been shown to increase the risk of cardiovascular disease (http://blog.doctoroz.com/dr-oz-blog/why-we-were-wrong-l-carnitine).
Now, my recommendation to you is to reduce as much as possible the consumption of red meat as it has been to shown to be very rich in both L-carnitine and choline, which are precursors of TMAO.
Finally, results of this study show how much of an impact the gut bacteria has on our overall health. The gut microbiota represents a new target for therapeutic manipulation and targeting for the treatment and prevention of cardiovascular diseases.
1.”Facts about Heart Disease." Facts about Heart Disease | The Heart Research Institute - Heart Research Institute. Heart Research Institute, n.d. Web. 25 June 2017.
2. "What Causes Heart Disease?" National Heart Lung and Blood Institute. U.S. Department of Health and Human Services, 21 Apr. 2014. Web. 25 June 2017.
3. Jonsson, Annika Lindskog, and Fredrik Bâckhed. "Role of Gut Microbiota in Atherosclerosis." Nature Reviews Cardiology 14.2 (2016): 79-87.
4. Tang, W.h. Wilson, and Stanley L. Hazen. "The Contributory Role of Gut Microbiota in Cardiovascular Disease." Journal of Clinical Investigation 124.10 (2014): 4204-211.
Pain is medically defined as “an unpleasant sensation that can range from mild, localized discomfort to agony.” (1) Now, there are a few types of pain and the classification of it is a whole study in itself. One that we will particularly focus on is called visceral pain. It is one of the most common types associated with disease and also one of the most frequent reasons why patients go see a doctor. This type refers to a pain that results from the activation of nociceptors, sensory neurons that send pain signals to the brain, of the thoracic, pelvic, or abdominal viscera (organs).
True visceral pain is characterized as a vague, diffuse, and poorly defined sensation. Patients tend to report a vague sensation of malaise. (2) It is important to go and visit a medical specialist if this type of sensation continues over a lengthy period of time. Treatment of the pain in many circumstances should be deferred until the origin of the symptoms has been identified. Masking pain may confound the diagnostic process and delay the recognition of life-threatening conditions. (3)
An emerging study these days is the link between our gut bacteria and visceral pain. Studies have shown that the absence of gastrointestinal (GI) bacteria, such as which occurs in germ free (GF) mice, is associated with a reduced perception of pain following different inflammatory stimuli. (4) Thus, these mice, which are devoid of bacteria colonizing their gut, do not perceive pain under the same conditions that ‘normal’ mice would. Furthermore, modulation of the intestinal microbiome by administration of various probiotics also has been shown to alter pain responses. (5)
Now, this doesn’t only work on a physiological level, but a genetic one as well. The microbiome (the ensemble of genes of the microbiota) can influence both peripheral and central neurological activity by a variety of mechanisms. The early neonatal period is a critical time for the development of the nervous system, including the enteric (gut) nervous system. Recent studies comparing the development of the enteric nervous system in GF mice and specific pathogen-free mice suggest that the intestinal microbiota plays an important role in shaping this process. (6) It is thanks to our nervous system that we are able to perceive different stimuli such as temperature, pressure, and pain. Therefore, our gut microbiota is essential in shaping the framework through which we recognize when we are injured or hurt.
A lot of these studies have been performed within animal models which have been useful to demonstrate potential mechanisms by which the microbiome can modulate visceral pain responses. In GF mice, contact with commensal (co-existing without causing harm) microbiota is necessary for mice to develop pain sensitivity. (7) The mechanisms by which the gut microbiota is capable of inducing or reducing visceral hypersensitivity are slowly being uncovered. It is clear that stress either chronic or in early life is a key factor in potentiating visceral pain responses and its associated comorbidities.
Earlier, we mentioned that visceral pain is one of the most common types associated with disease. Here is an example of how this works. Visceral pain is a known complication in patients suffering from irritable bowel syndrome (IBS). These patients tend to experience a lot of hypersensitivity. IBS is characterized by chronic abdominal pain and discomfort. Growing evidences suggest that IBS patients have a dysbiotic (abnormal) intestinal microbiota. Approximately 8% of children experience recurrent functional abdominal pain and about 61% of these children continue to report abdominal pain or IBS. (8) IBS patients show an altered profile of gut microbiota composition. Earlier studies found that the intestinal microbiota in IBS patients differs from that in healthy individuals, with a consistent decrease in the Bifidobacterium spp. population and an increase in the Enterobacter population. Other studies in patients with IBS have shown alterations in the microbiota, such as an increased ratio of Firmicutes to Bacteroidetes and a reduction in Lactobacillus species. Symptoms of IBS may be linked to those alterations. (7) Therefore, the types of bacteria present within our gut are of great importance in determining whether or not one is more susceptible to disease.
In summary, the microbiome, gut and brain have a complex set of interactions that modulate responses to visceral pain. Various psychological, infectious and other stressors can disrupt this harmonious relationship and alter both the microbiome and visceral pain responses. If you are ever suffering from an unknown sense of malaise, it is important to go seek the advice of a health professional. It may be more serious and more complex than you know!
1. Medicine Net. "Medical Definition of Pain." MedicineNet. MedicineNet, 2016.
2. Procacci P, et al. In: Cervero F, Morrison JFB (Eds). Visceral Sensation, Progress in Brain Research, Vol. 67. Amsterdam: Elsevier, 1986, pp 21–28.
3. Giamberardino MA. In: Devor M, et al. (Eds). Proceedings of the 9th World Congress on Pain, Progress in Pain Research and Management, Vol. 16. Seattle: IASP Press, 2000, pp 523–550.
4. Amaral, F. A., D. Sachs, V. V. Costa, C. T. Fagundes, D. Cisalpino, T. M. Cunha, S. H. Ferreira, F. Q. Cunha, T. A. Silva, J. R. Nicoli, L. Q. Vieira, D. G. Souza, and M. M. Teixeira. "Commensal Microbiota Is Fundamental for the Development of Inflammatory Pain." Proceedings of the National Academy of Sciences of the United States of America. U.S. National Library of Medicine, 12 Feb. 2008. Web.
5. Verdú, E. F., P. Bercik, M. Verma-Gandhu, X. X. Huang, P. Blennerhassett, W. Jackson, Y. Mao, L. Wang, F. Rochat, and S. M. Collins. "Specific Probiotic Therapy Attenuates Antibiotic Induced Visceral Hypersensitivity in Mice." Gut. U.S. National Library of Medicine, Feb. 2006. Web.
6. Borre, Y. E., G. W. O'Keeffe, G. Clarke, C. Stanton, T. G. Dinan, and J. F. Cryan. "Microbiota and Neurodevelopmental Windows: Implications for Brain Disorders." Trends in Molecular Medicine. U.S. National Library of Medicine, Sept. 2014. Web.
7. Chichlowski, Maciej, and Colin Rudolph. "Visceral Pain and Gastrointestinal Microbiome." Journal of Neurogastroenterology and Motility. Korean Society of Neurogastroenterology and Motility, Apr. 2015. Web.
8. O'Mahony, S. M., J. R. Marchesi, P. Scully, C. Codling, A. M. Ceolho, E. M. Quigley, J. F. Cryan, and T. G. Dinan. "Early Life Stress Alters Behavior, Immunity, and Microbiota in Rats: Implications for Irritable Bowel Syndrome and Psychiatric Illnesses." Biological Psychiatry. U.S. National Library of Medicine, 01 Feb. 2009. Web.
I’m always on the lookout for new ways to improve my health, whether it be through diet, exercise or — the all-too-often neglected third member of the U.S. Army’s Performance Triad — sleep. And while some health trends border the edge of insanity (Tapeworms, anyone?), others have a fair share of scientific literature backing up their claims.
One such trend that has slowly but surely began to establish its niche in pop culture is intermittent fasting (IF). If it sounds familiar, you may have seen this video circulating on your Facebook newsfeed. While there are a handful of IF variations that exist (and you can read all about those here), they are all usually adapted to serve one common purpose — to encourage weight-loss by moderately decreasing our calorie intake by 500-1000 calories per day.
Sounds crazy, right?
Well, maybe not.
The National Institute of Health (that’s the largest biomedical research institution in the world!) concluded that low-calorie diets can lower total body weight by an average of 8% in the short term (3-12 months), and that these low-calorie diets maintain significant weight loss over a 5-year period (1) (and that’s important, because “yo-yo dieting”, or the failure to maintain weight-loss, correlates with increased body fat (2)).
But the effects of caloric restriction, at least in mice, seem to extend far beyond weight loss to include more subtle health-promoting advantages. First suggested 82 years ago by C.M. McCay (3), a research team headed by J.D. Han recently found that mice following a low-calorie diet (defined as 30% less calories than usual) were healthier and lived 20-25% longer than mice following a “normal”-calorie diet. Not only that, but these mice exhibited the lowest and most stable body weight and fat content, as well as the best metabolism (4).
Despite these exciting findings, researchers couldn't figure out why low-calorie diets increased overall health — until 2013, when Liping Zhao and his research group studied the gut bacteria in mice that followed a low-calorie diet their entire lives. Zhao and his colleagues demonstrated that calorie restriction selected for certain gut bacteria, such as Lactobacillus, whose presence in our gut correlates with longer lifespan, while also reducing the amount of gut bacteria that are associated with decreased lifespan (5). In other words, it seems that reducing our daily calorie intake promotes the growth of “good” bacteria that prevent aging, while at the same time inhibiting the growth of “bad” bacteria that makes us age quicker.
But how can gut bacteria influence our lifespan? While the answer to this question isn’t obvious, we still have a pretty good idea of what is likely happening, and it involves the process of inflammation. We’ve all seen inflammation in action — when you get a paper cut, you’ll notice your skin becoming red, warm and painful. This is the result of immune cells (and blood) rushing to the site of the cut to kill the bacteria that are trying to enter your body. This kind of inflammation doesn’t last long (a few hours to a few days), and the bacteria are promptly killed (that’s a good thing!).
Here’s the problem: something different — and more destructive — can happen inside our bodies. Our gut is littered with bacteria, and while most of them aren’t recognized by our immune system, some of them are, and this kind of inflammation can last an abnormally long time. That’s dangerous: long-term (or “chronic”) inflammation is known to speed-up the deterioration of the cardiovascular system (6), as well as increase the incidence of stroke and cognitive loss at younger ages (7). In other words, chronic inflammation shortens our lifespan.
And guess what — meals high in calories have been associated with increases in chronic, lifespan-crippling inflammation (8).
That’s why eating less calories seems to increase lifespan in mice. Zhao found that a low-calorie diet encouraged the growth of anti-inflammatory gut bacteria while simultaneously inhibiting the growth of pro-inflammatory bacteria (5). That means that by eating less (~500 fewer calories per day), we can potentially decrease chronic inflammation, thereby living longer, healthier lives.
1. Strychar, I. 2006. Diet in the management of weight loss. CMAJ 174: 56-63.
2. Mackie, G. M., D. Samocha-Bonet, and C. S. Tam. 2017. Does weight cycling promote obesity and metabolic risk factors? Obes. Res. Clin. Pract. 11: 131-139.
3. McCay, C. M., M. F. Crowell, and L. A. Maynard. 1989. The effect of retarded growth upon the length of life span and upon the ultimate body size. 1935. Nutrition 5: 155-171; discussion 172.
4. Zhou, B., L. Yang, S. Li, J. Huang, H. Chen, L. Hou, J. Wang, C. D. Green, Z. Yan, X. Huang, M. Kaeberlein, L. Zhu, H. Xiao, Y. Liu, and J. D. Han. 2012. Midlife gene expressions identify modulators of aging through dietary interventions. Proc. Natl. Acad. Sci. U. S. A. 109: E1201-1209.
5. Zhang, C., S. Li, L. Yang, P. Huang, W. Li, S. Wang, G. Zhao, M. Zhang, X. Pang, Z. Yan, Y. Liu, and L. Zhao. 2013. Structural modulation of gut microbiota in life-long calorie-restricted mice. Nature communications 4: 2163.
6. Danesh, J., P. Whincup, M. Walker, L. Lennon, A. Thomson, P. Appleby, J. R. Gallimore, and M. B. Pepys. 2000. Low grade inflammation and coronary heart disease: prospective study and updated meta-analyses. BMJ 321: 199-204.
7. Wilson, C. J., C. E. Finch, and H. J. Cohen. 2002. Cytokines and cognition--the case for a head-to-toe inflammatory paradigm. J. Am. Geriatr. Soc. 50: 2041-2056.
8. Blackburn, P., M. Cote, B. Lamarche, C. Couillard, A. Pascot, A. Tremblay, J. Bergeron, I. Lemieux, and J. P. Despres. 2003. Impact of postprandial variation in triglyceridemia on low-density lipoprotein particle size. Metabolism 52: 1379-1386.
Alzheimer’s disease (AD) is the most common form of dementia (disorder affecting the brain) in the western world. However, there is no cure available for this devastating neurodegenerative disorder. This disease is characterized by proteins called beta amyloid (Aβ) which build up in the brain to form structures called ‘plaques’ and ‘tangles’ (1). This leads to the loss of connections between nerve cells, and eventually to the death of nerve cells and loss of brain tissue. Since Alzheimer’s is a progressive disease, this means that gradually, over time, more parts of the brain will be damaged. As this happens, more symptoms develop and become more severe. Some of the symptoms of Alzheimer’s are memory loss, confusion, inability to learn new things, hallucinations and impulsive behavior (2).
But what does Alzheimer’s disease have to do with the gut microbiota?
Increasing evidence suggests that the gastro-intestinal tract is the bridge between microbiota and the central nervous system. As a matter of fact, a growing body of clinical and experimental evidence suggests that gut microbiota may contribute to aging and influence brain disorders (3). For instance, a new connection between gut microbiota and Parkinson’s disease has been reported in humans. In mouse models, studies report a role for the microbiota in the modulation of stress-related behaviors relevant to psychiatric disorders as mentioned in one of our previous blogs (You can read that blog here http://www.thegutguys.com/myhealth/the-worried-gut-can-gut-bacteria-influence-our-mood).
Similarly, recent studies have showed marked differences in the gut bacteria composition between mice suffering from Alzheimer's and healthy mice (4). Researchers also studied Alzheimer’s disease in mice that completely lacked bacteria to further test the relationship between intestinal bacteria and the disease. The results showed that mice without bacteria had a significantly smaller amount of beta amyloid plaques in the brain (recall: Beta-amyloid plaques are the lumps that form at the nerve fibres in cases of Alzheimer's disease).
Furthermore, in order to clarify the link between intestinal bacteria and the occurrence of the disease, the researchers transferred intestinal bacteria from diseased mice to germ-free mice (meaning mice free of bacteria), and discovered that the mice developed more beta-amyloid plaques in the brain compared to if they had received bacteria from healthy mice (4). Overall, that’s all a very scientific way to say that a healthier gut appears to lead to both a lower incidence of Alzheimer’s and a less severe form of the disease when it does occur.
These are very promising results and they have the potential for opening new area for the treatment and prevention of Alzheimer’s disease and ultimately other neurodegenerative disorders. In fact, researchers will continue to study the role of bacteria in the development of Alzheimer's disease, and test entirely new types of preventive and therapeutic strategies based on the modulation of the gut microbiota through diet and new types of probiotics.
1. Park, Laibaik, Ken Uekawa, Lidia Garcia-Bonilla, Kenzo Koizumi, Michelle Murphy, Rose Pitstick, Linda H. Younkin, Steven G. Younkin, Ping Zhou, Geroge A. Carlson, Josef Anrather, and Costantino Iadecola. "Brain Perivascular Macrophages Initiate the Neurovascular Dysfunction of Alzheimer AÎ² Peptides." Circulation Research (2017): n. pag.
2. Society, Alzheimer's. "Alzheimer's Disease." Alzheimer's Society. Alzheimer's Society, 11 Nov. 2016. Web.
3. O’Toole, P. W. & Jeffery, I. B. Gut microbiota and aging. Science 350, 1214–1215, (2015).
4. Harach, T., N. Marungruang, N. Duthilleul, V. Cheatham, K. D. Mc Coy, G. Frisoni, J. J. Neher, F. FÃ¥k, M. Jucker, T. Lasser, and T. Bolmont. "Reduction of Abeta Amyloid Pathology in APPPS1 Transgenic Mice in the Absence of Gut Microbiota." Scientific Reports 7 (2017): 41802.
Cancer is not a particular disease, but rather a term used to group many related diseases (1). This group of diseases is responsible for a large number of deaths worldwide and represents a serious health threat today. Cancerous cells are defined by an uncontrolled cell proliferation – they continuously divide and ignore signals telling them to stop, to the point of forming a tumor. A tumor is referred to as being malignant only if it is capable of spreading throughout the body of the patient. Thus, from a single cell, the entire body can be invaded by malignant tumors (1).
The human host’s immune system tolerates trillions of microorganisms. The bacteria that comprise the gut microbiota line the walls of the intestine and live in a mutually beneficial equilibrium within the host. Meanwhile, the immune system is constantly on the lookout for harmful pathogens that may contribute to disease. It’s safe to say that there’s a perfect and fragile balance existing within our gut. However, when this equilibrium is broken, a number of negative consequences can ensue. One of them is the risk of oncogenesis (formation of cancer) and tumour progression (2).
This break in the equilibrium, also referred to as dysbiosis, can be caused by a number of factors. The arrival of pathogenic (harmful) organisms as well as several environmental (aging, hormones, antibiotics) and genetic (defects in the intestinal immune system) factors promote dysbiosis (2). Not only can these factors affect the risk of colorectal cancer, but the gut microbiota can also promote oncogenesis on a systemic level and lead to breast and hepatocellular (liver) cancers (3).
We’ve seen how disequilibrium in relation to our gut microbiota can affect the risk of tumorigenesis (formation of tumours). On the other hand, it is possible to influence the microbiota for therapeutic purposes. Recent data has suggested that the gut microbiota is capable of modulating the response to cancer therapy and the susceptibility to toxic side effects (4). Commensal organisms are responsible for absorbing and metabolizing drugs. Furthermore, direct interaction with bacteria can affect the efficacy of chemotherapeutic drugs (4). Many of the mechanisms by which the gut microbiota affects inflammation, immunity, carcinogenesis (development of cancer) and response to therapy at the local level have been characterized.
One challenge for clinicians is to determine the best microbiota composition for each condition. The ultimate goal is to discover a bacterial species or a combination of species that both reduces systemic toxicity and promotes anticancer therapy. Thus, targeting the microbiota in cancer and other diseases is likely to become one of the next frontiers for precision and personalized medicine (4).
Metabolic diseases such as diabetes and obesity are becoming a major concern for all countries. In developing countries such as South Asia, which are affected by the highest rate of population growth, the social system cannot afford the corresponding expenses. One of the major consequences linked to the occurrence of these metabolic diseases is the rapid increase in cardiovascular events leading to death (1). Therefore, in Western countries, where metabolic diseases are firmly established, as well as in Eastern countries, where diabetes and obesity are strongly emerging, there is a crucial need to identify the risk factors of diabetes and obesity and to find new therapeutic targets.
What is Type I Diabetes?
In Type I Diabetes, the body’s immune system attacks part of its own pancreas. In fact, the immune system ,more specifically T cells — which are a type of immune cells that destroys foreign particles, recognizes the insulin-producing cells in the pancreas as foreign and destroys them. This type of attack is known as autoimmunity. The insulin-producing cells, also called “islets”, are the cells that sense glucose in the blood and, in response, produce the necessary amount of insulin to normalize blood sugars. Without insulin, sugar builds up in the blood. If left untreated, the high level of blood sugar can damage the eyes, kidneys, nerves, and heart (2).
Gut Microbiota and Diabetes
A high incidence of Type I Diabetes has now plagued developed countries for several decades, where environmental conditions have dramatically changed (3).
Recent research has shown the critical role of the gastrointestinal microbiota in both the protection and development of Type I Diabetes. The discovery of the role of intestinal microbiota came from the observation that the incidence of spontaneous Type I Diabetes in a certain type of mouse colony can be affected by the microbial environment in the animal housing facility or by exposure to microbial stimuli such as injection with mycobacterium (a type of bacteria) or various microbial products (4).
Studies on rats have shown that bacterial species such as Lactobacillus johnsonii and Lactobacillus reuters prevented the development of Type I Diabetes. Moreover, observations following the administration of antibiotics in Type I Diabetic rat models showed that the occurrence of the disease was reduced, strengthening the hypothesis that a specific intestinal microbiota composition can induce autoimmune diseases, including Type I Diabetes.
Thus, prevention of Type I Diabetes can, in the future, be based on interventions targeting the gut microbiota.