Project Background

Colorectal Cancer

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

Short Chain Fatty Acids (SCFAs)

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
• Maintain an acidic luminal pH, which prevents the production and absorption of carcinogenic factors
• Boost 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-heamoglobinopathies
• Inhibiting cholesterol production, preventing hypercholesterolemia
• Reducing insulin resistance, preventing type II diabetes

The relationship between butyrate and colorectal cancer

Butyrate has been shown to inhibit cell proliferation and induce apoptosis in carcinoma cell lines by hyper-acetylating histones through inhibition of histone deacetylase (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 tumor mass formation ₇.

People consuming typical Western diets do not consume enough dietary fibre. For example, the average American only consumes 8 g a day; far less than the recommended 20 to 30 g per day ₈. In addition, the species that comprise the the microbiome differs between individuals; some individuals have fewer bacteria that contain the butyrate biosynthetic pathway. The most abundant butyrate-producing bacterial species were are Eubacterium rectum and E. halliii 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.

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, Boushey R 2009 Colorectal Cancer Epidemiology: Incidence, Mortality, Survival, and Risk Factors. Clinics in Colon and Rectal Surgery. 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 HL. Resistant starch content in a selection of starchy foods on the Swedish market. European Journal Of Clinical Nutrition. 2002 June; 56(6): p. 500-505

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

5. Canani RB, Di Costanzo M, Leone L, Pedata M, Meli R, Calignano A. Potential beneficial effects of butyrate in intestinal and extraintestinal diseases. World Journal of Gastroenterology. 2011 March 28; 17(12): p. 1519-1528.

6. Bajkaa BH, Clarkea JM, Toppinga DL, Cobiacc L, Abeywardenaa MY, Patten GS. Butyrylated starch increases large bowel butyrate levels and lowers colonic smooth muscle contractility in rats. Nutrition Research. 2010; 30: p. 427-424.

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

8. Murphy MM, Douglass JS, Birkett A. Resistant starch intakes in the United States. J Am Diet Assoc. 2008 Jan;108(1):67–78.

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