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

3D illustration Intestinal villi. Intestine lining. Microscopic capillary. Human intestine. Concept of a healthy or diseased intestinal. Viruses, bacteria, cell infected organism, decreased immunity

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

A quick look at how 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 has 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 dysbiosis2-3

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, like regulating pH inside the intestine, improving nutrient absorption, inhibiting pathogen growth, and feeding certain cells in our body4.  SCFAs 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 SCFAs?

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

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

scfas feed our cells and affect our health

An important function of SCFAs 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 cancers5-7, can decrease levels of adiposity and improve insulin sensitivity8-10 (Figure 1).

butyrate
Figure 1. Selected health aspects influenced by the SFCA butyrate. Arrows represent an increase or decrease, respectively, of the condition after treatment with butyrate.

In contrast, the SCFA 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 SCFAs 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 infants had lower levels of all three SCFAs (acetate, propionate, and butyrate)11.
  • Intestinal permeability – the SCFA 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 help improve the function of intestinal cells12-13
  • Anticancer function – studies using human cancer cells lines have found that butyrate can increase the function of certain genes associated with some cancers14-15.
  • Inflammatory responses – Studies have shown the SCFAs 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 SCFAs in your gut is greatly influenced by the diet you follow as well as other lifestyle factors. Consulting with a physician and testing your gut microbiota is an important first step to elucidate your SCFA profile and create a pathway to improve your health.

References

  1. Valdes AM, Walter J, Segal E, Spector TD. Role of the gut microbiota in nutrition and health. Bmj. 2018 Jun 13;361:k2179. Read it!
  2. Martinez KB, Leone V, Chang EB. Western diets, gut dysbiosis, and metabolic diseases: Are they linked?. Gut microbes. 2017 Mar 4;8(2):130-42. Read it!
  3. Carding S, Verbeke K, Vipond DT, Corfe BM, Owen LJ. Dysbiosis of the gut microbiota in disease. Microbial ecology in health and disease. 2015 Dec 1;26(1):26191. Read it!
  4. Ríos-Covián D, Ruas-Madiedo P, Margolles A, Gueimonde M, de los Reyes-Gavilán CG, Salazar N. Intestinal short chain fatty acids and their link with diet and human health. Frontiers in microbiology. 2016 Feb 17;7:185. Read it!
  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.
  6. Elimrani, I.; Dionne, S.; Saragosti, D.; Qureshi, I.; Levy, E.; Delvin, E.; Seidman, E.G. Acetylcarnitine potentiates the anticarcinogenic effects of butyrate on SW480 colon cancer cells. Int. J. Oncol. 2015, 47, 755–763. Read it!
  7. Bordonaro, M.; Lazarova, D.L.; Sartorelli, A.C. Butyrate and Wnt signaling: A possible solution to the puzzle of dietary fiber and colon cancer risk? Cell Cycle 2008, 7, 1178–1183. Read it!
  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!
  12. Kelly CJ, Zheng L, Campbell EL, Saeedi B, Scholz CC, Bayless AJ, et al. Crosstalk between microbiota-derived short-chain fatty acids and intestinal epithelial HIF augments tissue barrier function. Cell Host Microbe. (2015) 17:662–71. doi: 10.1016/j.chom.2015.03.005. Read it!
  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!
  16. Vinolo MA, Rodrigues HG, Hatanaka E, Sato FT, Sampaio SC, Curi R. Suppressive effect of short-chain fatty acids on production of proinflammatory mediators by neutrophils. The Journal of nutritional biochemistry. 2011 Sep 1;22(9):849-55. Read it!