The Human Colon in Evolution: Part 4, The Secrets of Butyrate


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 Another hypothesis is that lack of SCFAs is behind such diseases of civilization. A SCFA called butyrate provides some insight into this. Butyrate is the preferred fuel of the colonic epithelial cells and also plays a major role in the regulation of cell proliferation and differentiation (Wong, de Souza, Kendall, Emam, & D. J. a Jenkins, 2006). Lower than normal levels have been found in patients with several diseases, notably types of colitis and inflammatory bowel disorder. Studies show such diseases can be treated through application of butyrate in the colon. That and the fact that some studies show complete remission through bacteriotherapy transplants point to these diseases being caused by disturbed populations of gut bacteria. Interestingly, these diseases are common in captive populations of apes and unheard of in wild apes (McKenna et al., 2008).

Bacteria affect butyrate production, but so do dietary inputs. Certain fibers produce more butyrate than others in humans, whether or not this differs between primates would be an interesting avenue of research (Smith, Yokoyama, & German, 1998).

Figure 1: Butyrate production in response to fiber

Interestingly, one of the top producers is something known as “resistant starch.” Resistant starch represents the growing nuance in understanding of fiber, since it is a starch that acts like a fiber in terms of acting as a bacterial substrate. It first showed up on the scientific radar when scientists found that low rates of colon cancer were not just found in populations with high-fiber diets, but those with high-starch diets (O'Keefe, Kidd, Espitalier-Noel, & Owira, 1999)1. Researchers found that a particular starch resisted digestion and ended up being fermented by colonic flora. They called this resistant starch and it is found mostly in cooked starches, some raw starches like green bananas, and some rough unprocessed grains and seeds. The former is termed type III and is a major part of the diets of many foraging populations who consume pounded and cooked starches like cassava, taro, true yam, and sago palm.

Whether or not humans are better adapted to certain types of resistant starch remains unexplored, but could account from some inconsistent results in studies that used type I resistant starch, mostly found in grains and seeds that would have probably been relatively uncommon in our ancestral diet. These studies have shown poor results and others with promising results are marred by high drop out rates due to unpleasant gastrointestinal side effects (Rinne et al., 2005; de Vrese & Marteau, 2007; Vuksan et al., 2007). Whether some populations would do better on this type of starch versus others would be an interesting investigation, but very few cultures consume large amounts of unmilled seeds and grains.

What type of starch we are best adapted to is interesting because the role of starch in human evolution is so controversial. Richard Wrangham has suggested that utilization of cooked starches was one of the dietary quality innovations that fed our rapidly expanding expensive brain tissue as it evolved towards hominid size (Wrangham, 2003). Recent analysis throws a wrench in that theory because it suggests habitual use of fire came after encephalization, about 300,000 years ago (Roebroeks & Villa, 2011). However, this does not mean that such cooked starches did not change humans, even if it reduces their significance in human evolution.

The burgeoning field of archeological starch grain analysis has transformed our view of hominids once thought to be mostly carnivorous. Microfossils on Neanderthal teeth from around 44,000 years ago show evidence of the consumption of many roots and tubers, some of which show evidence of cooking (Henry, Brooks, & Piperno, 2010). The full impact of the adoption of cooked starches on the human body has not been fully elucidated. One promising adaptation is the starch-digesting salivary amalyse gene, AMY 1 (Perry et al., 2007). Chimpanzees and bonobos have only two copies of this gene, humans have as many as 10 copies, though it varies quite heavily by population from 2 to 10 correlated with the importance of starch in the diet. Molecular genetic evidence places the origin of divergence on this gene at about 200,000 years, about the time when habitual fire use became common. Further genetic analysis shows that adaptations to root and tuber starch as a major source of calories may account for variation in human folic acid metabolism, since folic acid is usually low in starchy vegetables (Hancock et al., 2010).

Another relatively unexplored avenue of research would be whether butyrate in the diet itself has led to decreased reliance on butyrate for colonic fermentation in some cultures that consume large amounts of dietary butyrate. The major source of butyrate in food is from the milk fats of grazing animals (Smith et al., 1998).

It is most common in the modern diet in butter at 3%. It is possible that pastoral cultures consume substantial amounts of exogenous butyrate. Currently there have been few studies on oral consumption of butyrate in humans. Animal studies have been inconclusive, with some showing positive effects and some showing negative effects, which is complicated by the fact that if ingested orally it is also present in the small intestine, where it may play different roles (Sengupta, Muir, & Gibson, 2006; Wächtershäuser & Stein, 2000). A small study found orally-administered butyrate had a positive effect on symptoms of Crohn’s disease, but the method of administration was through pills rather than food (Di Sabatino et al., 2005).

Another potential source of butyrate is fermented foods. Some fermented foods like ogi, a pounded fermented starch, contain measurable levels (Hesseltine, 1979). Fermented foods are worth examining evolutionarily because they represent another human dietary innovation in improving food quality. Fermentation increases the bioavailability of nutrients, breaks down starches, and reduces levels of anti-nutritional factors and toxins (Mugula, 2003). It is unknown how long humans have been purposefully fermenting food. Fermentation naturally occurs in the wild and many wild animals are known to indulge in such foods to the point of drunkenness (Dudley, 2002). Spontaneous fermentation and consumption of such foods by wild primates is unfortunately not well studied. However, fermentation is practiced by almost every known culture to some extent, with the largest diversity in fermented foods among African farmers (Dirar, 1993) It is estimated that fermented foods make up 1/3 of the diet of humans worldwide (van Hylckama Vlieg, Veiga, Zhang, Derrien, & Zhao, 2011). Exogenous fermentation may substitute for the reduced fermentative ability of the human gut.

1. The researchers concluded that colon cancer risk was increased with meat consumption. I will remain skeptical until they do studies on other cultures that eat relatively low-fiber and high-meat diets like the Masai and Siberian cultures for example.

Di Sabatino, A., Morera, R., Ciccocioppo, R., Cazzola, P., Gotti, S., Tinozzi, F. P., et al. (2005). Oral butyrate for mildly to moderately active Crohnʼs disease. Alimentary pharmacology & therapeutics, 22(9), 789-94. doi: 10.1111/j.1365-2036.2005.02639.x.

Dirar, H. A. (1993). The indigenous fermented foods of the Sudan: a study in African food and ... (p. 552). CAB International. Retrieved May 9, 2011, from

Dudley, R. (2002). Fermenting fruit and the historical ecology of ethanol ingestion: is alcoholism in modern humans an evolutionary hangover? Addiction (Abingdon, England), 97(4), 381-8. Retrieved from

Hancock, A. M., Witonsky, D. B., Ehler, E., Alkorta-Aranburu, G., Beall, C., Gebremedhin, A., et al. (2010). In Light of Evolution IV: The Human Conditions Sackler Colloquium: Human adaptations to diet, subsistence, and ecoregion are due to subtle shifts in allele frequency. Proceedings of the National Academy of Sciences of the United States of America, 107(Supplement_2), 8924-8930. doi: 10.1073/pnas.0914625107.

Henry, A. G., Brooks, A. S., & Piperno, D. R. (2010). Microfossils in calculus demonstrate consumption of plants and cooked foods in Neanderthal diets (Shanidar III, Iraq; Spy I and II, Belgium). Proceedings of the National Academy of Sciences of the United States of America, 1-6. doi: 10.1073/pnas.1016868108.
Hesseltine, C. W. (1979). Some important fermented foods of Mid-Asia, the Middle East, and Africa. Journal of the American Oil Chemists’ Society, 56(3), 367-374. Springer Berlin / Heidelberg. doi: 10.1007/BF02671501.

Hylckama Vlieg, J. E. van, Veiga, P., Zhang, C., Derrien, M., & Zhao, L. (2011). Impact of microbial transformation of food on health-from fermented foods to fermentation in the gastro-intestinal tract. Current opinion in biotechnology, 22(2), 219-211. doi: 10.1016/j.copbio.2010.12.004.

McKenna, P., Hoffmann, C., Minkah, N., Aye, P. P., Lackner, A., Liu, Z., et al. (2008). The macaque gut microbiome in health, lentiviral infection, and chronic enterocolitis. PLoS pathogens, 4(2), e20. doi: 10.1371/journal.ppat.0040020.

Mugula, J. (2003). Microbiological and fermentation characteristics of togwa, a Tanzanian fermented food. International Journal of Food Microbiology, 80(3), 187-199. doi: 10.1016/S0168-1605(02)00141-1.

OʼKeefe, S. J., Kidd, M., Espitalier-Noel, G., & Owira, P. (1999). Rarity of colon cancer in Africans is associated with low animal product consumption, not fiber. The American journal of gastroenterology, 94(5), 1373-80. doi: 10.1111/j.1572-0241.1999.01089.x.

Perry, G. H., Dominy, N. J., Claw, K. G., Lee, A. S., Fiegler, H., Redon, R., et al. (2007). Diet and the evolution of human amylase gene copy number variation. Nature genetics, 39(10), 1256-60. doi: 10.1038/ng2123.

Rinne, M. M., Gueimonde, M., Kalliomäki, M., Hoppu, U., Salminen, S. J., & Isolauri, E. (2005). Similar bifidogenic effects of prebiotic-supplemented partially hydrolyzed infant formula and breastfeeding on infant gut microbiota. FEMS immunology and medical microbiology, 43(1), 59-65. doi: 10.1016/j.femsim.2004.07.005.

Roebroeks, W., & Villa, P. (2011). On the earliest evidence for habitual use of fire in Europe. Proceedings of the National Academy of Sciences of the United States of America, 1018116108-. doi: 10.1073/pnas.1018116108.

Sengupta, S., Muir, J. G., & Gibson, P. R. (2006). Does butyrate protect from colorectal cancer? Journal of gastroenterology and hepatology, 21(1 Pt 2), 209-18. doi: 10.1111/j.1440-1746.2006.04213.x.

Smith, J., Yokoyama, W., & German, J. B. (1998). Butyric Acid from the Diet: Actions at the Level of Gene Expression. Critical Reviews in Food Science and Nutrition, 38(4), 259-297. doi: 10.1080/10408699891274200.

Vrese, M. de, & Marteau, P. R. (2007). Probiotics and Prebiotics: Effects on Diarrhea. J. Nutr., 137(3), 803S-811. Retrieved May 9, 2011, from

Vuksan, V., Whitham, D., Sievenpiper, J. L., Jenkins, A. L., Rogovik, A. L., Bazinet, R. P., et al. (2007). Supplementation of conventional therapy with the novel grain Salba (Salvia hispanica L.) improves major and emerging cardiovascular risk factors in type 2 diabetes: results of a randomized controlled trial. Diabetes care, 30(11), 2804-10. doi: 10.2337/dc07-1144.

Wong, J. M. W., Souza, R. de, Kendall, C. W. C., Emam, A., & Jenkins, D. J. a. (2006). Colonic health: fermentation and short chain fatty acids. Journal of clinical gastroenterology, 40(3), 235-43. Retrieved from

Wrangham, R. (2003). “Cooking as a biological trait.” Comparative Biochemistry and Physiology - Part A: Molecular & Integrative Physiology, 136(1), 35-46. doi: 10.1016/S1095-6433(03)00020-5.

Wächtershäuser, a, & Stein, J. (2000). Rationale for the luminal provision of butyrate in intestinal diseases. European journal of nutrition, 39(4), 164-71. Retrieved from


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