Short-Chain Fatty Acids

What are Short-Chain Fatty Acids?

Short-Chain Fatty Acids (SCFA) are tiny but powerful molecules which are created as a byproduct of fiber fermentation by our gut microbiota in the large intestine. In a beautifully symbiotic relationship, when we feed our beneficial gut bacteria their preferred high-fiber foods, they reward us by producing SCFAs which promote our health and longevity.

SCFAs have numerous health benefits.
They keep us lean and encourage healthy metabolism.
They reduce our risk of obesity and type 2 diabetes.
They decrease systemic inflammation,
improve digestive health,
and support our immune system.
They lower our risk of cardiovascular disease and cancer,
and they help protect our brains
from neurodegeneration and dementia.

Acetate, Propionate, and Butyrate are the three most studied SCFAs and account for 95% of the SCFAs produced by our gut microbiota. They are comprised of short chains of carbon, hydrogen, and oxygen atoms. SCFAs have their greatest direct affect within the large intestine itself, but they can also enter the bloodstream via the portal vein and be carried by various transporters to the liver and other organs. In addition, they indirectly stimulate numerous beneficial actions in a wide variety of body systems (Wu et al., 2021).

(Annunziata et al., 2020)

(Nogal & Valdes, 2021)

How Do We Promote Short-Chain Fatty Acid Production?

When we eat dietary fiber (which can only be found in plant foods), it travels through the stomach and small intestine until it reaches our large intestine where our wonderful gut microbes are eagerly awaiting its arrival. All fiber-rich plant foods (including legumes, whole grains, vegetables, fruits, nuts, and seeds) help to promote SCFA production by our beneficial microbes. However, their favorite food is resistant starch.

Resistant starch is a type of starch in which the molecule is tightly packed and “resistant” to digestion by enzymes in the small intestine. Given that we don’t possess the enzymes to digest it, resistant starch remains intact until it can be consumed and fermented into SCFAs in the microbiome. Think of resistant starch as a protective travel pod around a starch molecule, allowing it to glide safely through our stomach and small intestine until it gets to its final destination in the large intestine where it can be opened in a way that is beneficial to both our good gut bugs and our health.

Foods that are naturally high in resistant starch, include:

• Beans, peas, and lentils (white beans and lentils have the highest levels)

• Plantains and green bananas

• Whole grains (especially oats and barley)

In addition, there are a few whole plant foods that we can manipulate to increase their resistant starch levels. For example, the glucose units in hot, just-cooked rice have a loose structure, making them easy to absorb in the small intestine. When cooled, the molecules rearrange themselves into very tight bonds that are resistant to digestion. This occurs with potatoes, sweet potatoes, rice, and pasta, which all gain resistant starch as they cool. Cooking these foods in advance and then refrigerating them overnight will alter how they are digested and will allow their starch molecules to travel into the large intestine to be fermented into SCFA by our gut microbes. Reheating the food, does not destroy the resistant starch once it is formed.

Beneficial Actions of Short-Chain Fatty Acids

SCFAs Improve Metabolic Function
SCFAs can help us to maintain a healthy body weight and improve our metabolism. They promote fatty acid oxidation (use of fat for fuel), they reduce the storage of fat in our adipose tissues, they help shrink the size of our adipose cells, and they increase thermogenesis (heat production) leading to higher fat burning (He et al., 2020). In essence, the more we encourage SCFA production by consuming a fiber-rich diet, the better our bodies become at processing our food so that we stay lean and our metabolism is revved and efficient.

SCFAs Reduce Obesity Risk
In addition to improving our metabolic functioning, SCFAs have a protective effect against excess weight gain by regulating appetite, suppressing food intake, inhibiting de novo lipogenesis (creation of fat from carbohydrates), discouraging lipid (fat) synthesis, and decreasing triglycerides in our liver. When we regularly consume high-fiber plant foods, we are less hungry, we stay full longer, cravings are reduced, our circulating blood lipids (cholesterol and triglycerides) more easily fall into the normal range, and creation of additional fat is minimized.

SCFAs are Anti-Diabetic
SCFAs reduce insulin resistance, improve insulin sensitivity, and promote glucose homeostasis by helping to suppress blood sugar spikes (Portincasa et al., 2022). By lowering glucose concentrations in the bloodstream and discouraging insulin resistance, the risk of developing type 2 disabetes is reduced.

Abbreviations: GLP-1 = glucagon-like peptide 1; GPcrs = G protein-coupled receptors;
HDAc = histone acetylation; PYY = peptide YY (Li et al, 2017)

The graphic above illustrates the many ways in which SCFAs are beneficial for metabolic health, weight maintenance, and diabetes prevention. Starting at the lower left, we can see that non-digestible dietary fibers (from plant foods) feed our gut microbes which ferment them into SCFAs. These fuel our colonocytes (a type of epithelial cells that line the large intestine). They also stimulate intestinal gluconeogenesis (formation of glucose in the intestine from proteins and fat). Intestinal gluconeogenesis is important in weight maintenance as it helps us to control our food intake. Following intestinal gluconeogensis, sensors in the intestine relay satiety signals to our brains which signal us to stop eating. Intestinal gluconeogenesis has also been demonstrated to be a primary factor in enhancing insulin sensitivity throughout the body (Mithieux et al., 2009). Insulin sensitivity is critical in diabetes prevention.

In addition, SCFAs stimulate Enteroendocrine L-cells (specialized endocrine cells found within the GI tract, stomach, and pancreas) to release the hormones PYY and GLP-1. These hormones promote satiety and suppress appetite. GLP-1 also stimulates the production of insulin and decreases the creation of glucagon in the pancreas. Both of these actions encourage the uptake of glucose into our muscles and adipose tissues, which results in lower circulating blood glucose levels and reduced diabetes risk. SCFAs can also decrease fatty acid synthesis (less formation of new fat) and promote fatty acid oxidation in the liver (burning of the fat we eat instead of storing it in adipose tissue). SCFAs inhibit lipolysis (the breaking down of triglycerides into fatty acids and glycerol), thereby decreasing free fatty acids and reducing circulating cholesterol. SCFAs also promote the secretion of leptin, the satiety hormone, which further suppresses appetite and promotes weight loss (Li et al, 2017).

SCFA are Cardioprotective
While our scientific understanding of the relationship between cardiovascular disease and SCFAs is still evolving, SCFAs appear to promote heart health through four primary pathways:

• SCFAs Improve Gut Barrier Function
  Gut dysbiosis, proliferation of pathological gut microbes, and poor gut barrier integrity have been linked with heart disease formation and progression. SCFAs nourish our enterocytes (intestinal cells which absorb nutrients, water, and the beneficial substances). They also also increase mucin production (a protein mucus layer which lubricates and protects the GI tract). Mucin helps to maintain the tight junctions in our gut barrier and prevents harmful bacteria from entering our bloodstream. SCFAs also promote anti-microbial peptide, which helps to destroy any pathogens which may have arrived on our food. They also lower the PH of the intestine, causing increased acidity, which further contributes to destruction of unwanted pathogens. Finally, SCFAs help lower levels of bacterial endotoxin lipopolysaccharide (LPS), a harmful bacteria which increases systemic inflammation and can damage blood vessels (Nogal & Valdes, 2021; Katsimichas et al., 2019).

• SCFAs Reduce Systemic Inflammation and Improve Immune Health
  A wide array of disease processes, including cardiovascular disease, are linked with systemic inflammation and poor immune health. In addition to maintaining an intact gut barrier, which is a critical component of our immune system, SCFAs increase the number of T cells in the gut, which provide a first line defense against invading viruses and pathogens. SCFAs also promote anti-inflammatory cytokines interluken (IL), which defend against pro-inflammatory cytosine invaders (Chen et al., 2019; Nogal & Valdes, 2021; Vinolo et al., 2011).

• SCFAs Improve Lipid Profiles and Glucose Homeostasis
  Metabolic syndrome, obesity, high cholesterol, and type 2 diabetes are all significant risk factors for the development of heart disease. In the ways delineated above, SCFAs improve glucose regulation, promote healthy weight maintenance, reduce risk of diabetes, and lower circulating cholesterol. Through their positive impact on metabolic health, SCFAs lower risk of developing heart disease, as well as improving heart healing for those who have already experienced a cardiac event (Chen et al., 2019).

• SCFAs Modulate Blood Pressure
  Although findings on SCFAs and blood pressure are mixed, with some researchers reporting elevations in blood pressure and others demonstrating blood pressure reduction, the general consensus in the literature appears to be that SCFAs have a modulating influence on blood pressure, encouraging it to move into the normal range. Acting through the sympathetic nervous system, SCFAs can stimulate vasoconstriction. This tightening of the blood vessels increases heart rate, augments blood flow to skeletal muscles, and increases blood pressure during times of threat or intense exercise. Working through the parasympathetic nervous system, SCFAs can cause vasodilation, or a relaxation of blood vessels, which leads to a lowering of blood pressure. Researchers are currently exploring SCFA supplementation as a means of reducing hypertension (Wu et al., 2021; Xu et al., 2022).

(Nogal & Valdes, 2021)

(Chen et al., 2019)

SCFA are Anti-Cancer
In addition to improving immune function and reducing systemic inflammation, both of which are critical to decreasing the proliferation of cancer cells, SCFAs have also been shown to suppress tumor growth and cancer cell metastasis (Son et al., 2023). SCFAs, especially butyrate, appear to inhibit cancer growth via their regulation of apoptosis (cellular death), autophagy (cellular clean-up of dysfunctional cells), improved metabolism, EMT processes (disruption of cellular adhesion which lowers the risk of metastasis), and triggering of tumor-suppressing genes in several types of cancers (Son et al., 2023).

Of particular interest, SCFAs have been demonstrated to heighten the efficacy of cancer treatments, providing a synergistic effect wherein traditional treatments are more successful and patients experience less drug resistance. Individuals who respond well to chemotherapy, immunotherapy, and radiotherapy have been show to have a higher abundance of butyrate and a greater number of SCFA-producing bacteria than those who do not show good treatment responses. Use of SCFAs as a supplemental therapy alongside more traditional cancer treatments is an exciting new avenue of research (Al-Qadami et al., 2022; Son et al., 2023).).

(Al-Qadami et al., 2022)

SCFA are Neuroprotective
While research on SCFAs and brain function is in its infancy, there is accumulating evidence that they positively impact the functioning of neurons. SCFAs have been shown to modulate neurotransmitter levels and to promote neurotropic factors, which play an important role in learning and memory. SCFAs are also believed to have anti-aging, neuro-protective effects on brain cells. In mice studies, they have been shown to improve cognitive impairment and suppress neuro-inflammation in animals with Alzheimer's Disease (Qian et al., 2020). They also appear to reinforce the integrity of the blood brain barrier, helping to deter pathogens (Silva et al., 2020). In addition, SCFAs are important mediators of the gut-brain axis, influencing gut-brain communication. There are many exciting clinical implications for use of SCFAs in the treatment of neurodegenerative disorders, dementia, depression, and autism. It will be intriguing to see what clinical benefits can be found as the research progresses in this burgeoning new field (Mirzaei et al., 2021; Müller et al., 2021;Silva et al.,2020).

(Silva et al., 2020)

As we have seen, SCFAs promote optimal health across numerous bodily systems. In addition to those listed above, SCFAs reduce allergies, improve skin conditions, support our kidneys, and help to prevent fatty liver disease. They are particularly integral to gut health, solidifying the integrity of our gut barrier, reducing colon cancer risk, preventing constipation, and helping to maintain microbiome richness and diversity (Blaak et al., 2020; Bulsiewicz, 2020).

Best of all, the fiber-rich foods which are needed for SCFA production are delicious, satiating, and beautifully varied.
To gain the impressive health benefits of SCFAs,
simply eschew the ultra-processed food aisles
and reach instead for a wide array of
whole, unprocessed, fiber-rich, plant foods.

Wishing you abundant good health and happy eating.
🌱💕

References:

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