House of Carbs

Project Background

Colon Cancer

Colon (colorectal) cancer is the second most common cause of cancer death in the UK with 30,000 new cases being diagnosed every year₁. Epidemiological studies have shown that 90% of the risk factors for colon cancer are environmental rather than genetic, with diet have the biggest effect (see Figure 1). According to the US Food and Drug Administration, diets that are high in red meat and fat correlate to an increased risk of colon cancer, whilst the consumption of dietary fibre reduces the risk₂.

Resistant Starches

Resistant starches are carbohydrate molecules that, because of their structure, are not able to be fully digested by the carbohydrate degradation enzymes produced by the upper digestive system₃. These starches pass through the small intestine and are fermented by the colonic microbiome.

Figure 1: Lifestyle choices such as excessive consumption of alcohol, smoking tobacco, insufficient exercise, and a diet rich in meat and low in dietary fibre have been shown to be the major contributing factors for colonic cancers.

Short Chain Fatty Acids

Certain species of colonic bacteria produce short chain fatty acids (SCFAs) such as butyric acid during fermentation.
Butyrate, the conjugate base of butyric acid, has been shown to have many beneficial effects in health₄. For example:

In the intestine, butyrate;

• Is the major metabolic substrate for colonocytes. Without butyrate for energy, colon cells undergo autophagy.
• Maintains an acidic luminal pH, which prevents the production and absorption of carcinogenic factors.
• Boosts the mucosa of the gut and the immune system.

It also has several wider health benefits including;

• Inducing expression of fetal globin genes preventing β-haemoglobinopathies.
• Inhibiting cholesterol production and preventing hypercholesterolemia.
• Reducing insulin resistance and preventing type II diabetes.

The relationship between butyrate and colon cancer

Butyrate has been shown to inhibit cell proliferation and induce apoptosis in carcinoma cell lines by hyper-acetylating histones through inhibition of histone deacetylases (HDAC) and inducing gene silencing, leading to apoptosis ₅(see Figure 2). Studies in rats have shown that increasing the amount of butyrate in the gut resulted in a significant reduction in smooth muscle cell contractility, which lowers the risk of colon cancer ₆. Another study confirmed the direct correlation of increased butyrate in the colon with a reduced tumour mass formation ₇.

People consuming typical western diets do not consume enough dietary fibre. For example, the average American only consumes 8 g of dietary fibre a day; far less than the recommended 20 to 30 g per day ₈. In addition, the species that comprise the microbiome differ between individuals with some individuals having fewer bacteria that contain the butyrate biosynthetic pathway than others. The most abundant butyrate-producing bacterial species are Eubacterium rectale and E. hallii ₉.

The overall quantity of SCFAs produced in the colon is dependent on two factors:
1. The amount of resistant carbohydrate molecules that pass to the colon for fermentation by colonic bacteria.
2. Bacteria with SCFA biosynthetic pathways being present in the microbiome.

Figure 2: As well as supplying healthy colonic epithelial cells with energy, butyrate has been shown to inhibit histone deacetylases (HDAC) in carcinoma cell lines. This leads to hyper-acetylation of histones inducing silencing and triggering apoptosis.

Read about the two approaches House of Carbs is taking to increase the levels of butyrate in the colon by clicking here.

References

1. Haggar F., and Boushey R., 2009, Colorectal Cancer Epidemiology: Incidence, Mortality, Survival, and Risk Factors , 22(4), p. 191-197.

2. The United States Food and Drug Administration, 2015, https://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfcfr/CFRSearch.cfm?fr=101.76 [Accessed August 24 2015]

3. Elmståhl H.L., 2002, Resistant starch content in a selection of starchy foods on the Swedish market , European Journal Of Clinical Nutrition, 56(6), p. 500-505

4. Zeng H., Lazarova D.L., and Bordonaro M., 2014, Mechanisms linking dietary fiber, gut microbiota and colon cancer prevention , World Journal of Gastrointestinal Oncology, 6(2), p. 41-51.

5. Canani R.B., Di Costanzo M., Leone L., Pedata M., Meli R., and Calignano A., 2011, Potential beneficial effects of butyrate in intestinal and extraintestinal diseases , World Journal of Gastroenterology, 17(12), p. 1519-1528.

6. Bajkaa B.H., Clarkea J.M., Toppinga D.L., Cobiacc L., Abeywardenaa M.Y., and Patten G.S., 2010, Butyrylated starch increases large bowel butyrate levels and lowers colonic smooth muscle contractility in rats , Nutrition Research, 30, p. 427-424.

7. McIntyre A., Gibson P.R., and Young G.P., 1993, Butyrate production from dietary fibre and protection against large bowel cancer in a rat model , Gut., 34, p. 386-391.

8. Murphy M.M., Douglass J.S., and Birkett A., 2008, Resistant starch intakes in the United States , J Am Diet Assoc., 108(1), p 67–78.

9. Louis P., Young P., Holtrop G., and Flint H.J., 2010, Diversity of human colonic butyrate-producing bacteria revealed by analysis of the butyryl-CoA:acetate CoA-transferase gene , Environ Microbiol., 12(2), p. 304–14.