Welcome and I’m happy to have you back to Part Three of our Great Escape blog post series! Before we discuss specific natural approaches that you can try to keep your intestinal region healthy, let’s review two of our most frequently asked about concerns: I have a bad case of… Diarrhea: Diarrhea is an all too common symptom with a wide range of causes and repercussions. Infectious agents, overeating, incomplete digestion, food sensitivities, intestinal dysmotility, and sometimes more serious medical issues, are some of the common causes of diarrhea. Diarrhea can be classified as acute or chronic, and is further
Short chain fatty acids (SCFA) are produced by the gut microbiota largely in the large intestines or the colon. SCFA have numerous health properties including maintenance of good gut and brain health via the gut-brain axis but also in metabolic syndrome (MetS). This article discusses the effects on the latter.
Many of us are familiar with long chain fatty acids comprising 18 carbons to 22 carbon length, like the ones present in flax, hemp as well as olive, evening primrose, borage and fish oils. Omega 3 fatty acids include DHA and EPA which have been widely studied for benefits for the heart, brain and immune health. SCFA are much smaller in length 1 to 4 carbon length, and the three main ones are acetic, propionic and butyric acids produced in the ratio 3:1:1. Butyrate is considered the most important and most studied.
The gut microbiota consists of trillions of cells largely concentrated in the colon where food – especially complex carbohydrates in the form of fiber, resistant starches like inulin, guar gum, psyllium, and bran are digested. Humans lack the enzymes to break down these fibers, however; the microbes are able to break down the fibers to produce SCFA. In that light SCFA are often referred to as gut metabolites or biproducts. Various families of bacteria are responsible for producing SCFA including Akkermansia, Firmicutes, Faecalibacterium prausnitzii, Clostridium, Acetobacter, etc. In this regard the colon acts as a giant fermenter or bioreactor taking the nutrient soup of the small intestines and fermenting further into smaller molecules which are usually (but not always) more useful to the body.
Approximately 50 to 60 g of SCFA is produced daily in humans, but this is dependent on diet (the higher fiber intake the better). Other factors effecting SCFA production our bodies include antibiotic use, exercise, age, residence time of food in the gut and most importantly what we inherited from our parents during birth as well as type of birth (cesarian or natural).
SCFA are absorbed from the gut lumen by the intestinal cells or colonocytes and provide numerous health benefits including:
- Major energy source for the colonocytes to function properly and maintain good housekeeping
- Helps intestinal barrier integrity of the cells lining the gut (colonocytes) by maintaining the tightness of the tight junctions between adjacent colonocytes so that pathogenic bacteria or their metabolites cannot enter the blood circulation, and thus preventing the so called “leaky gut” syndrome
- Helps production of mucin around intestinal cells to thwart entry of any pathogenic bacteria
- Reduce inflammation
- Reduce risk of colon cancer
- Maintain pH so that pathogenic “bad” bacteria don’t proliferate
- Helps balance energy generation and expenditure of cells. The more the energy is used up compared to amount generated, the greater the weight loss.
- Act as signaling molecules or communicators with other systems like nervous, endocrine, immune, etc.
SCFA’s in Metabolic Syndrome
Metabolic syndrome comprises a group of related conditions like diabetes, high blood pressure, high cholesterol and obesity. The underlying mechanism for all the above related conditions is thought to be insulin dysfunction, namely the inability of cells to respond to insulin properly. This phenomenon is called insulin resistance. As a response to high blood glucose levels, insulin is produced by the beta cells of pancreas. Insulin’s role is to get glucose out of the blood stream where it can cause significant damage and into the cells. Insulin primarily signals muscle, fat and the liver cells to take glucose where it can be broken down for energy or stored in the body for later use.
It is well known that high dietary fiber intake protects against MetS. What is it about fiber that provides this protection? Many researchers believe that SCFA play a major role in such protection.
SCFA produced in the gut are quickly taken up by colonocytes and then absorbed into the blood stream where they can impact distant tissues like the kidneys, liver, heart, muscle and fat and other organs. In the pancreas, SCFA not only increase insulin secretion but also suppress another hormone glucagon which increases glucose levels. Both actions reduce overall blood glucose levels.
SCFA also stimulate secretion of several gut hormones like glucagon-like peptide-1 (GLP-1) and PYY both of which help with absorption of glucose into the cells. PYY also acts in the brain on satiety receptors to produce a feeling of fullness thereby reducing food intake. Again, production of these gut hormones reduces blood glucose levels.
Leptin is another hormone that is mainly produced by fat cells. It helps regulates food intake, body weight and energy metabolism by acting on the brain receptors as well as on the liver and brown fat cells. In the liver leptin stops production of glucose and instead converts it into glycogen a storage form of glucose. All these actions of leptin further support reduction of blood glucose levels. SCFA are known to increase leptin secretion which further reduces food intake and eventually blood glucose levels.
SCFA also play a major role in fat metabolism. Overall SCFA reduce fat by increasing breakdown (lipolysis) as well as reducing synthesis of fat. Another feature of SCFA is to increase heat production that helps burn more fat and reduce fat storage.
Inflammation is another key factor in MetS, potentially as a cause as well as keeping it going. In many cases inflammation may be low grade, simmering in the background, but its cumulative effect over a period takes its toll on the body and increases the risk of MetS. SCFA, especially butyrate, can stimulate the immune system by increasing not only the number and types of immune cells, but their maturation as well, which further helps reduce production of inflammatory mediators that are normally produced by poor diet, sedentary lifestyles and/or presence of pathogenic bacteria in the gut.
Blood Pressure (BP) Regulation
There are a large number of studies which show that high fiber diet may help reduce blood pressure. Several of these studies used butyrate and showed BP reduction possibly by reducing inflammation. Animal studies suggest that SCFA may also lower blood pressure by ACE the enzyme that causes high BP.
SCFA have long been suggested to protect against obesity by various mechanisms:
- Inducing a feeling of satiety and thereby reducing food intake through the production of gastric hormones PYY, GLP-1 and leptin which then act in the brain on satiety receptors thereby reducing food intake. In several studies giving SCFA via diet did not achieve satiety, perhaps because SCFA were degraded by stomach acids by the time they reached the colon where these gut hormones were generated. This points to the importance of delivering the SCFA directly to the colon otherwise the satiety effects are not seen.
- By increasing energy expenditure through turning on various thermogenic genes much like cranking up the thermostat in a house. Animal studies show that temperature, heart rate and body shivering are all increased by SCFA. This effect is likely mediated by the sympathetic or vagus nerve that connects the gut to the brain. This connection has proved to play an important role in controlling human feeding behavior since severing this nerve abolishes the effect. Two human studies have confirmed use of SCFA in raising the energy expenditure.
- Increasing metabolism in the body in various organelles like the mitochondria (a more metabolic), conversion of white adipose tissue to brown fat tissue and stimulation of skeletal tissue.
Polycystic Ovarian Syndrome (PCOS)
PCOS is a very common female disorder affecting approximately 10% of women in the reproductive age. PCOS is a collection of diseases again categorized by insulin resistance which then results in diabetes, higher cholesterol, heart disease, hyperandrogenism (facial hair, acne, increased testosterone production, etc.) and obesity. Studies have shown that there is a significant microbiome change in women with PCOS and those without PCOS. In the latter group there is significant production of SCFA by the microbiome. Human studies have shown that when women were supplemented with probiotics to improve SCFA production there was improvement of PCOS symptoms.
SCFA: Old Wine in a New Bottle
SCFA are the major energy source of the intestinal cells. Butyric acid is the most important and most studied in preventing insulin resistance and MetS. While various commercial probiotics like bifidobacterium or lactobacillus which are available, their mechanism of increasing butyrate is indirect and falls considerably short in terms of amount of butyrate generated. This is because they don’t produce butyrate themselves rather help growth of beneficial bacteria like Akkermansia, Firmicutes, Roseburia, etc. Which in turn produce butyrate. However, this takes time. A far better way would be to increase butyrate directly, quickly and in far higher concentrations right from the get-go. Fortunately, there is only one such probiotic on the market in North America called Probiotic-3.
Probiotic- 3 was developed and first launched in 1963 in Japan. The Japanese are world leaders in fermentation and probiotics. Probiotic-3 has three unique strains which collectively act as a probiotic, prebiotic and synbiotic. All in one combination is quite rare for any commercial product. In Probiotic-3 one of the strains is food for the other two strains and helps increase their population by 100 fold! The second strain produces acetate while the third produces butyrate in very high concentrations. This unique strain is called Clostridium butyricum and as the name suggests produces copious amounts of butyric acid.
Besides the above advantages, it is far better to use a strain that produces butyrate locally in the entire length of the colon to maximize benefits of butyrate without being degraded by the gastric juices. As mentioned earlier one of the drawbacks of ingesting butyrate orally is that it gets broken down by the stomach acids and it loses much of its benefits especially when it comes to providing a feeling of satiety.
In summary, Probiotic-3 is the probiotic of choice which can increase butyrate and acetate concentrations in large quantities locally and quickly. This unique product is a probiotic, a prebiotic and a synbiotic all in one. Probiotic-3 is widely used in Japan as a pharmaceutical as well as a health product. It has to date over 70 human clinical studies and over 60 years of clinical use throughout Asia. Probiotic –3 with its direct butyrate generation is an ideal product for metabolic syndrome especially in women with PCOS issues.
Skonieczna-Zydecka K et-al, “Gut Biofactory- Neurocompetent metabolites within the gastrointestinal tract. A scoping review” Nutrients 2020, 12: 3369
He Jin et-al, “Short-Chain fatty acids and their association with signaling pathways in inflammation, glucose and lipid metabolism” Int J Molecular Sci. 2020, 21, 6356
Li Wei-Zheng et-al, “Gut microbiota and diabetes: From correlation to causality and mechanisms” World J of Diab, 2020, 15: 11(7) 293-308
Borycka-Kiciak K et-al, “Butyric acid- a well-known molecule revisited” Gastroenterology, 2017: 12(2):83-89.
Banasiewicz T et-al, “Determination of butyric acid dosage based on clinical and experimental studies” Gastroenterology Rev 2020: 15(2):119-125
Canfora EE et-al, “Short chain fatty acids in control of body weight and insulin sensitivity” Nat Rev Endocrinology, 2015, 11: 577-591
He Fang-faang and Li Yu-mei, “Role of gut microbiota in the development of insulin resistance and mechanism underlying polycystic ovary syndrome: a review” J of ovarian res, 2020, 13: 73
Li Z et-al, “Butyrate reduces appetite and activates brown adipose tissue via the gut brain neural circuit”, Gut, 18;67:1269-1279
Chambers ES et-al, ‘Role of gut microbiota generated SCFA in metabolic and cardiovascular health” Curr Nutr Rep 2018,;7:198-206
Cleophas MCP et-al, ‘Effects of oral butyrate supplementation on inflammatory potential of circulating peripheral blood mononuclear cells in healthy and obese males”. Sci Rep 2019;9:775
Noureldein M et-al, “Butyrate modulates diabetes-linked gut dysbiosis- epigenetic and mechanistic modifications”. J Mol Endocrinol 2020;64:29-42
Larasati RA et-al, “The role of butyrate on monocyte migration and inflammation response in patients with type 2 diabetes”. Biomedicine 2019;7