Microbes : The Gut-Brain-Skin Link

Following up on my previous post in which I wrote of gastrointestinal (GI) microbiota and its role in inflammation, hunger signaling and obesity, I would now like to expand on this area to examine the intricate link between our GI health, our mental and emotional states, as well as the quality of our skin, as influenced by dietary intake.

The gut-brain-skin axis is not a novel hypothesis. As far as 70 years ago, dermatologists John H. Stokes and Donald M. Pilsbury first concluded that emotional and mental distress could upset the delicate balance of microbiota in our digestive tracts, thereby causing inflammation. It was then suggested that bacterial induced inflammation increased GI permeability (what is now known as the "leaky gut"), setting the stage for systemic and local inflammation such as skin problems. 

During that same period, research also showed about 40% of individuals in a study with acne often produced insufficient amounts of stomach acids, which attracted movement of harmful bacteria from the lower GI, i.e. the colon, to the upper parts of the GI, causing an imbalance of beneficial microflora. At the same time, another study found low levels of "good bacteria" in the feces of patients with mental disorders, further substantiating the link between gut and brain health.

Today, this theory is gaining even more momentum as modern day diets wreck havoc in our digestive systems, ruining the natural balance of gut microflora. Consequently, we are seeing rising incidences of gastrointestinal disorders such as bloating, diarrhea, constipation, irritable bowel syndrome, gastric reflux. Through multiple ways, gut health has also been known to cause depression, anxiety, chronic fatigue, as well as skin disorders such as acne vulgaris, rosacea, dermatitis.

According to a recent report published in an issue of Gut Pathogens, underproduction of stomach hydrochloric acid (hypochlorhydria) encourages the growth of bad bacteria, a condition known as small intestinal bacterial overgrowth (SIBO). Manifestations of this condition bear wide-ranging degrees of seriousness, from bloating, diarrhea, constipation, to severe malabsorption (1).

SIBO was also detected in those individuals afflicted with fibromyalgia and chronic fatigue syndrome. Furthermore, SIBO could lead to competition for nutrients from excess bacteria and as a result, cause the malabsorption of macronutrients, B vitamins and other micronutrients. Additionally, SIBO was closely linked to emotional disturbances such as depression and anxiety. It was reported that those who were afflicted with acne rosacea were 10 times more likely to possess conditions of SIBO, when compared with individuals of healthy skin.

Gastrointestinal Permeability, a.k.a. leaky gut, was yet another condition closely associated with acne vulgaris. Bacterial toxins from the gastrointestinal tract were often observed in the blood stream of acne sufferers, strongly suggesting a compromised gastrointestinal tract which allowed such toxic materials to cross the tight junctions lining intestinal walls, over into the circulatory system. Both increased gut permeability as well as irritable bowel syndrome have also been evidenced to associate with depression and anxious behavior. 

According to the report, constipation was considered to be "the rule" in acne sufferers. A longer gut transit time also related positively with depression, which corroborated with an earlier study indicating that bacterial toxins caused depression-like behavior in mice.

Not only have Mental Health patients been reported to posses reduced levels of L.acidophilus, it appeared that the "mental health impairment" scores of mental patients were much higher if they simultaneously possessed conditions of acne vulgaris. Some researchers have also identified a specific group of psychological traits, referring them to what they called "the acne personality" which predicates that anxiety, depression and stress reactivity precedes disease onset of acne vulgaris. Hence, the triangle of influence between our gut-brain-skin can hardly be overstated.

Other observations reflected the direct correlation between increased dietary intake of western "sweet, fried, calorie-rich foods with low nutrient density" with both decreased beneficial microbiota in the gut, together with increased risk of acne. It was also duly noted that incidences of acne were extremely rare in hunter-gatherer communities even though such populations have vastly increased contact with soil organisms. Poor dietary habits such as adoption of the western diet led to the elimination of good bacteria in our digestive systems.

The efficacy of oral Probiotics in attenuating the gut-brain-skin inflammatory processes was also examined in the report. Administration of oral probiotics controlled the release of inflammatory properties in both skin and intestinal tract, and decreased both lesion counts and sebum production.  At the same time, the use of probiotics also increased levels of tryptophan, serotonin, dopamine as well as the production of omega-3 fatty acids in tissue cells, leading to significant improvements in feelings of depression, anger, anxiety as well as lowered cortisol. Application of oral probiotics influenced a peptide known as substance P, which was understood to be the mediator for communication between the gut, brain and skin. 

At this point, I would like to highlight some natural and delicious ways to add "friendly" microorganisms to our guts. In her revealing book Deep Nutrition, the author Dr Catherine Shanahan talked about the many virtues of adding fermented foods to our diets. According to Dr Shanahan, microbes in fermented foods "literally fight for our lives". In our bodies, they act as our defense against pathogens, improving our guts' ability to absorb nutrients. They also neutralize toxins which would otherwise be harmful, and in doing so, they themselves are transformed into nutrient powerhouses for our benefit. Dr Shanahan even mentioned an ancient Egyptian skin treatment using microbe-infused blends of fats as topical application (2).

Of course, this article would not be complete without a big warning on the detrimental effects of sugar consumption on gut microbiota, brain functions, and skin. Indeed, sugar (in ALL forms), is the chow of choice for pathogenic microorganisms. These microbes feasts on sugar, leading to an overgrowth of harmful microflora. Additionally, sugar has been known to be an immunity suppressant, making us susceptible to invading parasites, viruses and bacteria. 

Never mind that it is fine gourmet for germs, turns out that the "icing" on this icky cake also has direct damaging effects on our minds and skin. Sugar messes with the dendrites (branch like arms) on our brain cells and interferes with cell-to-cell communication, leading to Alzheimer's, dementia and learning difficulties.

And to top it all off, sugar glycates with proteins, literally creating a sticky mess in our bodies, causing tissue breakdown all over our bodies i.e. think wrinkly sagging skin, that under chin jowl, foggy brain, creaky joints, stiffening arteries etc. Yes, sugar makes us stupid AND old.

When I speak of avoiding sugar, the common reaction I get is "everything in moderation", as if swinging away to the left or right of some “sugar middle ground” would jeopardize our sensible balanced diets. Well, here’s the thing : First, that phrase is hackneyed, overrated and misused. It would only be meaningful if we applied it to something that is good for us to begin with. As in : Fish is good for us, therefore eat it in moderation. Second, sugar is a surefire way to get bad bugs, bad skin, bad moods (the list is still growing). Therefore, if it is indeed moderately bad bugs, moderately bad skin and moderately bad moods that we want, then I guess a moderate consumption of sugar would be apt! 

One last word, or three. Eat fermented food.

References:

1. Bowe WP, Logan AC. Acne Vulgaris, Probiotics and the Gut-Brain-Skin Axis - back to the future?. Gut Pathogens. 2011 Jan 31;3(1):1.
2. Shanahan Catherine, Shanahan Luke. (2009). Deep Nutrition: Why Your Genes need Traditional Food. Lawai, HI: Big Box Books.

The Ancestral Diet : an excellent model

"What causes fatness?"

Is this some kind of a joke? What kind of moron would ask such a question? Of course, the answer is in overeating and sedentary lifestyles, isn't it? If all fat people simply ate less and moved more, then they would be slim, wouldn't they? Isn't it also true that in order to lose weight, we must impose caloric restriction or increase caloric expenditure constantly (or better yet, do both concurrently)?

Lets do a little quiz here to test your obesity smarts. True or False?

1. All fat people are bad at math and cannot count calories.
2. All fat people are weak and lack the willpower to resist food. 
3. All fat people eat more and move less than all lean people.

If you have answered True to any of the above, I don't need to know. The case I am trying to make is that the causes and hence, the treatment of obesity are greatly misunderstood today. Understanding how we got so fat requires a paradigm shift because conventional wisdom didn't solve anything, and certainly does not look like it is about to provide answers anytime soon. 

In my opinion, Gary Taubes in his book Why we get fat and what to do about it, has struck the nail on the head (1). He states that conventional wisdom as it stands today, has failed miserably to explain the cause of obesity. Citing a "crowded room" example, Mr Taubes points out that saying "overeating causes obesity" is analogous to saying that too many people entered a room therefore it is crowded. It merely states the obvious and offers no meaningful explanation as to what caused so many people to enter the room, making it crowded. Indeed, why do we overeat? According to Mr Taubes, the common wisdom of fatness got it wrong way around, that it is because we are obese that we overeat.

You see, obesity is not just a state of being really fat, and overeating is not just a behavioral aberration. Obesity is characterized by a complex host of metabolic abnormalities and inflammation. These factors mess up satiety signals driving us to overeat and at the same time, they cause abnormal production and accumulation of fats. Therefore, we become obese because we eat the type of food which causes obesogenic conditions in the first place, which then cause us to overeat. 

Now, if the real mischief indeed originated from the type of food consumed, the next question which begs to be asked would naturally be what types of food?

In my attempt to find some answers, I'd like to take us a step back, and first look at the health promoting efficacy of ancestral/traditional diets. A recent paper published in “Diabetes, Metabolic Syndrome, Obesity” comparing western diets with ancestral diets drew the conclusion that ancestral diets consistently produced lean bodies, high level of satiety, and excellent health markers (2).

At this point, I would like to point out that most studies which examine obesity and its dietary causes have done so by isolating a small part of one picture and then analyze that isolated part against the backdrop of existing information. This is akin to running around in the same circle - there is usually a high degree of conformity with the conventions of the day and hardly leaves room for maneuvers in terms of shedding new light on the issue.

Indeed, by researching only the dietary habits of western populations in the hope of singling out one "culprit", most studies have ignored a realm of possibilities which lay outside the western diet. For e.g., studies of western populations have missed the important fact that even the western individuals classified as "healthy" possess dramatically higher levels of leptin (hunger signaling hormone), elevated fasting insulin levels (hormone involved with carbohydrate metabolization and glucose uptake), as well as higher blood glucose, than those on ancestral diets.

In contrast, this report offers a different approach. Comparisons of ancestral diets with the western diet allow us to : (i) get to the source of a good diet which is proven to produce remarkable health, vs one which causes ill health; (ii) distill the relevant dietary differences between the two; (iii) build a coherent theory based on those facts.

Now, let me provide some background on the physiology of food-related inflammation and what it means to be leptin resistant, as they relate to obesity.

Diet-induced inflammation, leptin resistance.

It is well established that obesity is characterized by chronic inflammation and many syndromes of metabolic abnormalities. Severity of these conditions are linked directly to the levels of microbes in our gastrointestinal tract (GI). Bacterial lipopolysaccharide (LPS), a substance that forms the outer membrane of a certain bacteria, causes our immunity to react strongly at high levels. At lower levels, it creates a chronic state of inflammation in our bodies.

Additionally, pathogen-associated molecular patterns (PAMP), which is essentially our innate immune systems's defense response to the shedding of pathogens harbored in our bodies, also plays an inflammatory role. Both LPS and PAMP have been implicated in many modern diseases, including liver toxicity, non alcoholic fatty liver disease and obesity. The gateway to such inflammatory substances is thought to be via our GI tract. Administration of antibiotics to reduce gut microbes in experimental rodents successfully reduced circulating LPS, improved inflammatory markers and glucose tolerance, and caused a reduction in body weight and fat tissue.

Moreover, information on satiety is transmitted via the vagal nerve that innervates our upper GI to the central nervous system, based on the physical and chemical actions of food in our guts. Leptin resistance begins to occur when leptin's ability to regulate the vagal nerve's sensitivity to satiety signals is blunted, while simultaneously increasing appetite-stimulating hormones. At a later stage, leptin resistance progresses to the central nervous system directly, as sensitivity of the hypothalamus diminishes.

What is an ancestral diet?

Data from ten populations of modern day hunter-gatherers, gathered throughout the late 1920s to 2006, consistently showed that those eating ancestral diets possessed lean bodies and virtually no metabolic abnormalities nor cardiovascular diseases. 

Of the ten populations, the Tarahumaras, Mexican Pimas and Arizona Pimas, whose diets included graduating degrees of western foods such as beans, maize/wheat/flour tortillas, processed meats, white bread, cereals, juices etc, saw corresponding increments in obesity, hypertension and diabetes.

Interestingly, ancestral diets that yielded good health outcomes spanned a very wide and different range of macronutrient compositions, dietary fiber, and nutrient density and glycemic index. For e.g., the Kitavans who subsisted on starchy root vegetables, leaves, fruit, with little fish, meat or fat, had a diet high in carbohydrates up to 70%. Conversely, the Masai's diet of cow's milk, blood and unprocessed meat, contained up to 66% saturated fats with cholesterol levels matching those of the U.S. Another important feature to note was the abundance of food available to these populations. There were neither food shortages nor caloric restrictions.

Yet, it did not seem to matter if some diets were high in carbohydrate while others ate mostly fats or protein ; or if one population consumed more calories than another; or if some diets contained little fiber; or even if they consumed foods that were high on the glycemic index. In spite of all these vastly different variables and the abundance of food, they all shared the same undifferentiated outcome - impeccable health markers with no incidences of obesity, hypertension, metabolic syndrome, and heart diseases.

What do genes and physical activity have to do with it?

Apparently, not as much as some of us would like to believe. From research, it appears that Kitavan islanders maintained their metabolic advantage only for as long as they ate their ancestral diets. Those islanders who transitioned into the western diet invariably became overweight.

Furthermore, historical data showed other hunter gatherers populations to develop signs of metabolic diseases once western foods were introduced, even though their physical activity remained high.

Carbohydrate density : the fundamental distinction.

It is quite clear that a western diet causes obesity while an ancestral diet does not. The most fundamental factor that distinguishes the western diet from an ancestral one is the "carbohydrate density" of the foods found commonly in the western diet.

"Carbohydrate density" is independent of the proportion of carbohydrate vs other macronutrients within the diet. It is evidenced that some ancestral diets contained a very high proportion of carbohydrates. However, sources of carbohydrates in these ancestral diet were in the form of tubers, fruits, leaves, stems etc. These cellular carbohydrates are stored within cell walls, and are able to retain most of its integrity throughout cooking and undergoes a longer digestive process. 

In contrast, acellular carbohydrates in the form of flour, sugar and processed foods, do not have the same "walled in" effect and hence, exert a very high concentration of  carbohydrate on our systems when consumed. The carbohydrate density of this new western diet burdens and confounds our GI in a way that ancestral diets do not, instigating the growth of new, harmful microbes in our guts that create toxic waste materials, and causes inflammation on top of leptin abnormalities. 

It should be noted that "carbohydrate density" is entirely different from "glycemic index" which measures the speed in which our blood glucose levels responds to dietary intake of carbohydrates. In fact, some ancestral foods consumed were high on the glycemic index, with no negative metabolic outcomes observed as long as they were cellular.

Although grains are cellular, they are considered a "carbohydrate dense" food. Due to their nature, storage of carbohydrates in grains was created for quick enzymic action to facilitate germination. Elevated levels of insulin and insulin resistance have been associated with obesity and diabetes. Since insulin is primarily mobilized by carbohydrate intake, dietary intake of carbohydrate dense foods might cause insulin irregularities.

Aren't whole grains healthy?

This is a difficult area to navigate where I honestly have no expert authority on. I can only report what I have read. As discussed above, grains are very dense in carbohydrates. There are some literature regarding allergenic and inflammatory properties found in grains (the most common being "gluten", the other being "lectin"). Personally, I exclude grains (even whole grains) from my own diet because I find that I have an adverse reaction to them. However, there are others I know who thrive well on whole grains, so all bets are off on this one. Suffice to say, my sentiments on refined grains and flour are not as flexible because I have absolutely nothing positive to say about them. The same can be said of sugar.

Here is what I have read. First, a study by The Pennsylvania State Universtiy in 2010, had shown only very modest improvements to heart diseases when refined grains were replaced with whole grains (3). This raises the questionability of the benefits of whole grains in this respect.

Second, as mentioned above, grains are "carbohydrate dense" foods, whereas carbohydrate sources of the ancestral diet were exclusively from consumption of vegetables including roots, leaves, bulbs, as well as fruits. In fact, when grains were introduced, signs of overweight or obesity and diabetes appeared.

Third, grain restricted diets have been evidenced to significantly improve metabolic markers and reduce weight. According to the report, these trials are small and few but results have been consistent and unanimous. All ad libitum (i.e. no voluntary caloric restrictions) studies of the modern day "Paleolithic diet", which mirrors the ancestral diet, appeared to be superior to the "Mediterranean diet" in reducing weight and waist circumference, better blood sugar regulation, and increased satiety per caloric intake prompting a voluntary decrease in caloric consumption. 

However, the benefits of the Paleo diet was independent of this spontaneous decrease in food intake and increased weight loss. When energy intake was controlled to be equal across the board, the Paleo diet still produced better markers including lower blood pressure and improved lipid profiles. Both diets similarly emphasize unrefined, whole foods but the fundamental difference lies in "grain restriction" of the Paleo diet.

Fourth, Leptin levels were also found to have fallen by 31% after 12 weeks, in another ad libitum study on the Paleo Diet, which had a linear relationship with decreased consumption of cereal grains. It has been hypothesized that cereal grain causes leptin resistance.

Doesn't dietary fat make us fat?

Without a doubt, dietary fat has some part to play in the obesity epidemic and metabolic disorders. In numerous rodent experiments on obesity, fat intake was elevated specifically to induce that condition. In addition, differing fatty acids have been successfully shown to create inflammatory processes in the body.

Even so, fat in itself is arguably not the primary cause of obesity. In fact, I think dietary fat (including saturated ones) is so important to the human body that, in many cases, insufficient intake is the real issue. But this is a much more complicated subject and warrants a separate discussion (one which I plan to undertake in another blog post). The only exceptions I take are trans fat and poor quality oils, which I can say in no uncertain terms, will not only make us fat but will, in fact, kill us.

According to this paper, the accusation that dietary fat as the primary causative factor of obesity is unfounded. If indeed dietary fat causes obesity, then wouldn’t a diet that is lower in fat eradicate the problem? But surprisingly, in ad libitum studies comparing low fat diets with low carbohydrate one, it is the low carbohydrate ones that emerged ahead with greater weight loss as well as greater improvements to metabolic markers. Low fat diets work as effectively as low carbohydrate diets only when caloric intake was controlled in both diets. The significance here is "satiety". Low carbohydrate diets led to a spontaneous and voluntary reduction in caloric intake whereas the low fat diet did not promote satiety, and hence would work only equally effective if there caloric intake was restricted.

Moreover, as discussed above, ancestral diets that were very high in meat and/or fat intake did not yield any metabolic disorders nor obesity among its consumers. This is inline with the observation that simply a high consumption of dietary fats from unprocessed sources, on its own does not have obesogenic effects on the human body.

However, fat (refined ones) has been implicated to cause a "double whammy" when consumed together with acellular flours, sugars, carbohydrate dense and processed foods, as is the case of the western diet. When ingested in this manner, fat enriches the inflammatory microbes already in place in our guts, and also increases PAMPs and absorption of bacterial LPS, stimulating even more inflammation.

Conclusion

The ancestral diet is one which promotes efficient human energy homeostasis. Historical data shows that those who maintain ancestral diets without the influence of western foods retain leanness of the body and excellent metabolic health markers, even when matched against "healthy individuals" in western populations. 

Since the ancestral diet is strongly distinct from the western diet with regard to "carbohydrate density", acellular refined foods and grains remain implicated as the main causes of inflammation, metabolic irregularities and obesity. The western diet which commonly features a combination of high carbohydrates and refined fats, creates an inflammatory microbiota in the gut and absorption of pathogenic materials, leading to leptin resistance and obesity. 

In addition, consumption of fructose appears to induce de novo lipogenesis (fat generation in the liver), liver toxicity and contributes to non alcoholic fatty liver disease. On the other hand, glucose appears to increase activity in fat tissue. Fructose and glucose are both components of sugar which is also very prevalent in the western diet.

Finally, insulin’s ability to regulate fat accumulation in fat tissue i.e. lipogenisis, from a carbohydrate rich meal that is typical of a western diet, has also been inextricably tied to the obesity epidemic today.

Discouraging as it sounds, maintaining an ancestral-like way of eating is actually within the reach for most folks. I am not suggesting that we all become Flintstones, and acknowledge that it is impossible to eliminate ALL offensive foods. But, I believe that we will reap health benefits even if we can do as much as minimize our exposure to problematic foods and at the same time, including as much as possible of the good stuff to our diets. Improvements will commensurate with the effort one puts in. In other words, it is not all or nothing. And ending on a note of encouragement : studies have shown that just after 7 weeks, the ill effects of the western diet was reversed markedly by consuming an ancestral diet !

References:

1. Taubes Gary. (2011). Why we get fat and what to do about it. New York: Anchor Books.
2. Spreadbury Ian. Comparison with ancestral diets suggests dense acellular carbohydrates promote an inflammatory microbiota and may be the primary cause of leptin resistance and obesity. Diabetes Metab Syndr Obes. 2012 Jul; 5:175-189
3. Harris KA, Kris-Etherton PM. Effects of whole grains on coronary heart disease risk. Curr Atherosclerosis Rep. 2010 Nov; 12(6):368-376.