September 17, 2014

Fiber, Bacteria, and Colorectal Cancer

Increasing fiber, gut microbiota may reduce cancer cell growth
In this observational cross-sectional trial matching patients with a diagnosis of advanced colorectal cancer to a healthy control group, the participants (N=5632) completed the food-frequency questionnaire and provided fecal samples. Participants with a high-fiber diet and more gut microbiota had diminished cancer-cell growth.

Reference

Chen HM, Yu YN, Wang JL, et al. Decreased dietary fiber intake and structural alteration of gut microbiota in patients with advanced colorectal adenoma. Am J Clin Nutr. 2013;97:1044-1052.

Design

Observational case control, cross-sectional designed trial matching patients with a diagnosis of advanced colorectal cancer (A-CRA) to a healthy control (HC) group

Participants

Study selected 5632 consecutive patients who had undergone colonoscopy from 5 medical centers in China. Of these subjects, 688 (344 in each of the A-CRA and HC groups) eligible subjects completed the food-frequency questionnaire and provided fecal samples.

Study Parameters

Dietary fiber intake, short-chain fatty acids (SCFAs), and gut microbiota in patients with advanced colorectal cancer were compared to the control group.

Primary Outcome Measures

SCFAs, microbiota, dietary fiber intake as related to A-CRA risk

Key Findings

This study identified several factors that were protective against A-CRA, including intake of vegetables and high amounts of fecal acetic acid and butyric acid. A high-fiber diet increased butyrate and butyrate-producing bacteria. The A-CRA group had significantly lower SCFAs in their stool. The major SCFA production in the HC group was acetate, followed by butyrate and propionate.
 
There was also a significant difference in the gut microbiota between the groups. Participants with A-CRA had higher levels of Enterococcus, Streptococcus, and Bacteroidetes and lower levels of Clostridium, Roseburia, and Eubacterium spp compared to the HC group.

Practice Implications

This study supports what has been reported in several cell culture and epidemiological studies: The right gut bacteria, fiber, and SCFAs may reduce colon cancer cell growth.
 
Fibers that initiate SCFA production from greatest to least are citrus pectin, soy fiber, sugar beet fiber, pea fiber, apple pectin, and oat fiber.1 Some of the possible protective effects of butyrate include its ability to nourish colonocytes, induce apoptosis, and increase glutathione transferases.2,3
Although more research is needed, practitioners might suggest citrus pectin, probiotics containing Lactobacillus and Bifidobacteria, and butyrate to reduce colon cancer risk.
Research has also supported the use of probiotics for reducing colon cancer cell growth in vitro and in vivo. Studies have supported the use of Lactobacillus species to decrease colorectal cell invasion.4 In patients with familial adenomatous polyposis, a 4-week intervention with the probiotic VSL#3, containing both Bifidobacteria and Lactobacillus strains, showed a reduction in cell proliferation and an increase in glutathione S-transferase (GST) enzyme, providing a protective benefit against colon cancer.5
 
Regarding fiber intake, human data supports the use of vegetable fiber in particular for reducing the risk of developing colon polyps. Another fiber that has been studied in animal models is inulin, which induced apoptosis in already transformed cells when used in the diet.
 
Although more research is needed, practitioners might suggest citrus pectin, probiotics containing Lactobacillus and Bifidobacteria, and butyrate to reduce colon cancer risk. I encourage my patients to eat a diet rich in vegetable fiber to increase the Bifidobacterium already present in their gut and thus SCFA production. These lifestyle and supplement interventions may provide the right fiber, gut bacteria, and SCFAs to reduce colon cancer cell growth and promote healthy colonocytes.

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References

  1. Titgemeyer EC, Bourquin LD, Fahey GC Jr, Garleb KA. Fermentability of various fiber sources by human fecal bacteria in vitro. Am J Clin Nutr. 1991;53(6):1418-1424.
  2. Scharlau D, Borowicki A, Habermann N, et al. Mechanisms of primary cancer prevention by butyrate and other products formed during gut flora-mediated fermentation of dietary fibre. Mutat Res. 2009;682(1):39-53.
  3. Hinnebusch BF, Meng S, Wu JT, Archer SY, Hodin RA. The effects of short-chain fatty acids on human colon cancer cell phenotype are associated with histone hyperacetylation. J Nutr. 2002;132(5):1012-1017.
  4. Escamilla J, Lane MA, Maitin V. Cell-free supernatants from probiotic Lactobacillus casei and Lactobacillus rhamnosus GG decrease colon cancer cell invasion in vitro. Nutr Cancer. 2012;64(6):871-878.
  5. Friederich P, Verschuur J, van Heumen BW, et al. Effects of intervention with sulindac and inulin/VSL#3 on mucosal and luminal factors in the pouch of patients with familial adenomatous polyposis. Int J Colorectal Dis. 2011;26(5):575-582.