title: Probiotics and the incidence of colorectal cancer: when evidence is not evident.
abstract: BACKGROUND
  Colorectal cancer (CRC) is the second major cause of death from cancer in Europe and in the USA. Dietary factors and colonic microflora seem to play an important role in colorectal carcinogenesis, making the potential protective role of probiotics of overwhelming interest. METHODS AND AIM: This article analyzes existing data from basic science (animal and in vitro models) and human (epidemiological and interventional) studies to highlight areas for which more evidence is necessary. We interrogated Medline for studies analysing the risk of CRC and the use of probiotics and also screened the references of identified papers.
  
  
  RESULTS
  As far as regards animal models, we identified 29 studies aimed at evaluating the effect of probiotics administration on the incidence of CRC and/or of precursor lesions. All but one study using an animal model with spontaneous tumour growth in the background of colitis employed carcinogens, and most studies employed Lactobacilli or Bifidobacteria. All but 3 studies had positive results, and when prebiotics were evaluated too, the combination led to an important synergistic effect. The protective effect of probiotics seemed more important when they were administered before, and not after the carcinogen, and the putative mechanisms are not fully elucidated. Five papers evaluated the effect of probiotics on CRC cell lines in vitro, with results suggesting the ability of probiotics to modulate important cell functions and in a complex interplay. There are few human epidemiological studies specifically designed to analyze the effect of probiotics on CRC incidence, with important confounding factors, such as role of fibers, other dairy products and vitamin D often present. Overall, these studies fail to detect significant effects of fermented milks against CRC. Interventional studies suggest reduction of surrogate markers for CRC risk. However, one recent study showed no significant difference in the development of new CRC following administration of either fibers or probiotics in patients previously treated for colon neoplasm. A single randomised, double blind, placebo controlled pilot interventional trial aimed to evaluate the reduction in cancer risk biomarkers obtainable with the consumption of a symbiotic has been designed and started but a complete final report is not yet available.
  
  
  CONCLUSIONS
  In our search of the literature few and conflicting epidemiologic data regarding the impact of fermented dairy products consumption in humans have been gathered. There are no positive data from interventional studies so far. Therefore, even though an ample body of evidence supports the potential anticarcinogenic action of probiotics on the basis of the results obtained in both in vitro and in vivo models, further evidence is very much needed.
authors.affiliation: Digestive and Liver Disease Unit, II Medical School, University La Sapienza, Rome, Italy.
authors.forename: Gabriele
authors.initials: G
authors.lastname: Capurso
authors.forename: Massimo
authors.initials: M
authors.lastname: Marignani
authors.forename: Gianfranco
authors.initials: G
authors.lastname: Delle Fave
mesh_terms: D000818:Animals; D015179:Colorectal Neoplasms / Q000382:microbiology*; D004195:Disease Models, Animal; D006801:Humans; D019936:Probiotics / Q000494:pharmacology