Pre and probiotics in colorectal cancer Prevention By Dalia Khamis El-Deeb

Pre and Probiotics in the prevention of colon-rectal cancer

Dalia Khamis El-DeebLecturer of Public Health

Community Medicine Department Alexandria Faculty of Medicine

ESPEN European Diploma of clinical nutrition

Points to be discussed

•History of pre and probiotics• Important definitions • Importance of pre and probiotics •Pre and probiotics in cancer colon prevention•Can synbiotics have a role in colon cancer

management as well ?

Death sits in the bowels; a bad digestion is the root of all evil” Hippocrates, 400 BC

• They were first identified and named by Professor Marcel B Roberfroid was a director at The Institute Of Food Research in 1995

History of Prebiotic

History of Probiotics

• At the start of the 20th century, Russian Nobel prize winner and father of modern immunology, Elie Metchnikoff, a scientist at the Pasteur Institute, was the first to conceptualize “Probiotics”

What are prebiotics and probiotics ?

Important definitions

• Prebiotic (Pre= Before and Biotic=life) Roberfroid offered a refined definition in the March 2007 stating "A prebiotic is a selectively fermented ingredient that allows specific changes, both in the composition and/or activity in the gastrointestinal microflora that confers benefits upon host well-being and health."


• Roberfroid stated that only two particular prebiotics then fully met this definition: • Trans-galacto-oligosaccharide• Inulin

Probiotics (Pro= Promoting and Biotic=life) • The Food and Agriculture Organization of the United Nation (FAO)

defines probiotics as“ live micro-organisms, which, when administered in adequate amount produce beneficial effect to the host when taken orally”.



• Synbiotic (Syn=Plus and Biotic=life a substance containing both a prebiotic and probiotic.

• Limited hydrolysis and absorption in the upper GIT(gastro-intestinal tract).• Selective growth stimulation of beneficial bacteria in the colon.• Immuno stimulation.• Stimulation of beneficial flora that promotes colonization

resistance.

Prebiotics

Preliminary research has demonstrated potential effects • On calcium and other mineral absorption• Immune system effectiveness bowel acidity • Reduction of colorectal cancer risk

and inflammatory bowel disease (Crohn's disease or ulcerative colitis • Hypertension and defecation frequency • Prebiotics may be effective in decreasing the

number of infectious episodes needing antibiotics and the total number of infections in children aged 0–24 months

Prebiotics

Probiotics

Probiotic microorganisms are:• Able to survive the passage through the digestive

system• Able to attach to the intestinal epithelia and colonize• Able to Maintain good viability• Able to utilize the nutrients and substrates in a

normal diet• Non-pathogenic and non-toxic• Capable of exerting a beneficial effect on the host

• "Lactic acid bacteria (LAB) and bifidobacteria are the most common types of microbes used as probiotics; but certain yeasts and bacilli may also be used. • The normal human digestive tract contains about 400 types of

probiotic bacteria that reduce the growth of harmful bacteria and promote a healthy digestive system.

Probiotics

Probiotics rich food



• Lactobacillus acidophilus• Lactobacillus ramnosus• Lactobacillus paracasei• Lactobacillus plantarum• Lactobacillus bulgaricus• Bifidobacterium infantis• Bifidobacterium longum• Bifidobacterium breve• Streptococcus Thermophilus

Common probiotic agents used as therapeutic options

Pre and probiotics in cancer colon prevention

Gut microbiota contribution

• Intestine is composed of over 1000 different bacterial species and the microbial population is heterogeneous in nature. • The microbial density within large

intestine is 12-fold beyond that in the small intestine. • So there is an estimated 12-fold increase

in cancer risk in the large intestine compared with the small intestine


• It has been revealed that microflora resident in colonic region are able to convert harmless compounds into metabolites that causes inflammation or tumourigenisis .• The microflora in intesitinal region can contribute to

carcinogenesis by producing enzymes like β-glucosidase, β-glucuronidase,nitroreductase and azoreductase .


• The most common pathogens associated with the production of β-glucuronidase are E.coli and Clostridium perfringens .• These faecal enzymes may hydrolyse glucuronide, a compound that

is needed to detoxify foreign compounds and produces cancer causing substances in intestinal lumen

Role of Probiotics in Colon Cancer Prevention

• Research has been conducted to explore the role of probiotics in colon cancer prevention. • How gut microbiota influence the development of colon cancer is unclear but the

gut micro biome contributes colon cancer through initiation of inflammation• Researchers suggested that the prevention of colon cancer might occur through

intervention of synbiotics (prebiotic+probiotic) that allow certain substantial changes in the gut micro biota .


• Upon fermentation of these prebiotics by beneficial microorganisms under anaerobic conditions they produce Short Chain Fatty-acids (SCFA) like butyrate, acetate, propionate of varying quantities. • It results in a decrease in pH and

thereby preventing overgrowth of pathogenic bacteria, which are pH sensitive in nature and it was based broadly on in vitro studies.


• These short chain fatty acids usually act as a source of carbon for colonocytes and they carry out important metabolic activities like • Modulation of bioactive food components, • Vitamin synthesis by intestinal microbiota. • Its function shapes the host intestinal

anatomy and also gut mucosal immune system


• Among these short-chain fatty acids, butyrate is found to play a defensive role in DNA oxidative damage induced by H2O2. • It may also decrease the altered cell proliferation and

induce programmed cell death process in altered cells


• Evidences have shown that some probiotic microorganisms Lactobacillus salivarius (L.salivarius) FP25, L. salivarius FP35, Pediococcus pentosaceus FP3 and Enterococcus faecium FP51 exhibited anti proliferative properties.• The proposed mechanism was given to the synergic induction by

directly adhering to colon cancer cells and triggering bio production of butyric and propionic short chain fatty acids.

Conclusion

• In conclusion, colon cancer, which in a high proportion of the population is due to somatic mutations occurring during the lifetime of an individual, could be retarded or prevented by preventing these mutations. • LAB and prebiotics that enhance LAB have been shown to deactivate

genotoxic carcinogens.

Conclusion

• In model systems in vitro they have been shown to prevent mutations. DNA damage has been prevented and chemopreventive systems may be stimulated in vivo in colon tissues. • From a mechanistic point of view, LAB offer potential as chemoprotective

agents and thus further research is clearly needed to quantify the beneficial effects for prevention of human colon cancer.

• The use of probiotics and prebiotics to prevent colon cancer has gained much attention due to positive outcomes from in-vivo and molecular studies. Various mechanisms have been proposed including its anticarcinogenic effects, antimutagenic properties, modification of differentiation processes in tumor cells, production of short chain fatty acids, and alteration of tumor gene expressions.

Conclusion

• Despite all the positive findings, other researches have also reported insignificant colon cancer protective effects. However, the increased interest in these areas demonstrated the need for further evaluation to better understand the exact mechanisms involved, and to generate uncontroversial experimental evidence.

Conclusion

Can synbiotics have a role in colon cancer management as well ?


• In one clinical trial, that underwent a 12 week double-blind placebo-controlled, randomized test with 37 colon cancer patients and 43 polypectomized patients, a synbiotic composition of (Lactobacillus rhamnosus GG, Bifidobacterium lactis Bb12+oligofructose enriched inulin) resulted in an increase of Lactobacilli & Bifidobacteria and decrease of C. perfringens in the gut microbiota. • Further, the production of interferon (IFN) -γ was increased by peripheral blood

mononuclear cells (PBMC) and reduced colorectal proliferation was observed in the cancer patients.

Still we need more evidence based research as it maybe A new field of Hope

Science

Pre and probiotics in colorectal cancer Prevention By Dalia Khamis El-Deeb