Short Chain Fatty Acids: the chemical language of the gut microbiota

A quick look at how short chain fatty acids and gut microbes communicate with our body.

There are trillions of microbes living in our intestines, including multiple species of bacteria, fungi, archaea, viruses, and protozoans. Collectively known as the gut microbiota, these microorganisms form a complex microenvironment, mostly dominated by bacteria.

Gut bacteria have been intensively studied over the past decades and it is now well established that these tiny inhabitants influence multiple aspects of human health and disease¹.

For example, imbalances in the number and diversity of gut bacteria, known as dysbiosis, have been linked to immunological malfunctions, inflammation, higher rates of infections, production of uremic toxins, and insulin resistance, among other problems. Diseases affecting the heart and kidney, diabetes, obesity, inflammatory bowel disease, and many other conditions also seem to be commonly associated with gut dysbiosis^2-3.

In recent years scientists have identified a group of chemicals known as Short Chain Fatty Acids or SCFAs that are produced by gut bacteria and have important roles in the functioning of our body. For example they are involved with regulating pH inside the intestine, improving nutrient absorption, inhibiting pathogen growth, and feeding certain cells in our body⁴. Short Chain Fatty Acids are produced by gut bacteria when they ferment certain types of fibre, like resistant starch, which cannot be digested in the stomach or small intestine. Instead, this type of fibre is digested in the large intestine, by trillions of gut bacteria.

WHAT ARE Short Chain Fatty Acids?

Short Chain Fatty Acids are technically defined as a short-chained carboxylic acid – a type of chemical structure that contains between 2 and 6 carbon molecules.

While Short Chain Fatty Acids are produced in some parts of the body, like in the liver, they are mostly produced in the large intestine, where gut bacteria generate them at high concentrations as a by-product of fibre fermentation.

The most abundant Short Chain Fatty Acids released in the colon are acetate, propionate, and butyrate. The proportion of these Short Chain Fatty Acids varies depending on different factors, such as which bacterial group is the most abundant, and external factors like diet and genetics of the human host where the gut bacteria live.

Short Chain Fatty Acids feed our cells and affect our health

An important function of Short Chain Fatty Acids is to provide energy to specific cells in our body. For example, butyrate is the main source of energy for colonocytes, cells that make up the colon wall, directly affecting their growth and differentiation. Furthermore, studies have suggested that butyrate has protective effects against colonic cancers^5-7, can decrease levels of adiposity and improve insulin sensitivity^8-10 (Figure 1).

In contrast, the Short Chain Fatty Acids propionate is metabolized and used by hepatocytes, cells found in the liver, whereas acetate is found not only in the liver but also in circulating blood.

Beyond the metabolic functions of Short Chain Fatty Acids in the body, these chemicals have also been associated with different diseases and conditions, including:

• Allergies – A study comparing allergic and non-allergic children found that allergic children had lower levels of all three Short Chain Fatty Acids (acetate, propionate, and butyrate)¹¹.
• Intestinal permeability – the Short Chain Fatty Acids butyrate has been shown to help promote the barrier function of epithelial cells in the intestine through various mechanisms. For example, butyrate can promote the expression of certain genes that improve the function of intestinal cells^12-13.
• Anticancer function – studies using human cancer cells lines have found that butyrate can increase the function of certain tumor-suppressor genes associated with some cancers^14-15.
• Inflammatory responses – Studies have shown the Short Chain Fatty Acids butyrate and acetate can inhibit inflammatory responses through their effect on specific genes that regulate the function of a special type of immune cells, called neutrophils¹⁶.

Regulation of the amount and diversity of Short Chain Fatty Acids in your gut is greatly influenced by the diet you follow as well as by other lifestyle factors. Consulting with a clinician and testing your gut microbiota is an important first step to elucidate your SCFA profile and create a pathway to improve your health.

References

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5. Encarnacao, J.C.; Abrantes, A.M.; Pires, A.S.; Botelho, M.F. Revisit dietary fiber on colorectal cancer: Butyrate and its role on prevention and treatment. Cancer Metastasis Rev. 2015, 34, 465–478.
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8. Gao, Z.; Yin, J.; Zhang, J.; Ward, R.E.; Martin, R.J.; Lefevre, M.; Cefalu, W.T.; Ye, J. Butyrate improves insulin sensitivity and increases energy expenditure in mice. Diabetes 2009, 58, 1509–1517. Read it!
9. Henagan, T.M.; Stefanska, B.; Fang, Z.; Navard, A.M.; Ye, J.; Lenard, N.R.; Devarshi, P.P. Sodium butyrate epigenetically modulates high-fat diet-induced skeletal muscle mitochondrial adaptation, obesity and insulin resistance through nucleosome positioning Br. J. Pharmacol. 2015, 172, 2782–2798. Read it!
10. Donohoe, D.R.; Garge, N.; Zhang, X.; Sun, W.; O’Connell, T.M.; Bunger, M.K.; Bultman, S.J. The microbiome and butyrate regulate energy metabolism and autophagy in the mammalian colon. Cell Metab. 2011, 13, 517–526. Read it!
11. Bottcher, M. F., Nordin, E. K., Sandin, A., Midtvedt, T., & Bjo¨ rkste´n, B. (2000). Microflora-associated characteristics in faeces from allergic and nonallergic infants. Clinical & Experimental Allergy, 30, 1591. Read it!
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13. Peng L, Li Z-R, Green RS, Holzman IR, Lin J. Butyrate enhances the intestinal barrier by facilitating tight junction assembly via activation of AMP-activated protein kinase in Caco-2 cell monolayers. J Nutr. (2009) 139:1619–25. doi: 10.3945/jn.109.104638. Read it!
14. Gupta N, Martin PM, Prasad PD, Ganapathy V. SLC5A8 (SMCT1)-mediated transport of butyrate forms the basis for the tumor suppressive function of the transporter. Life sciences. 2006 Apr 18;78(21):2419-25. Read it!
15. Miyauchi S, Gopal E, Fei YJ, Ganapathy V. Functional identification of SLC5A8, a tumor suppressor down-regulated in colon cancer, as a Na+-coupled transporter for short-chain fatty acids. Journal of Biological Chemistry. 2004 Apr 2;279(14):13293-6. Read it!
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