Chemopreventive effect of a probiotic preparation on the development of preneoplastic and neoplastic colonic lesions: an experimental study.
OBJECTIVE
A number of studies have suggested a key role played by certain resident gut bacteria in the development of large bowel cancer. The aim of the present study was to test the effect of a novel symbiotic preparation, which has been recently shown to beneficially modify gut ecosystem and systemic immunity, on either preneoplastic and neoplastic changes in a colon carcinogenesis model.


METHODS
Sprague-Dawley rats were fed a standard diet for 1 week and then were randomly assigned to three groups. The control diet was given to groups A and B, whereas in group C, the same diet plus 2 mL of a probiotic mixture was given throughout the experiment. Thirty rats (groups B, C) each received a weekly subcutaneous injection of azoxymethane at a dose of 15 mg/kg of body weight for 10 weeks. Group A served as a control group and received a subcutaneous injection of saline for 10 weeks. Forty-five rats were sacrificed at 3-week observation and 60 rats at 20-week observation for assessing metaphase index together with aberrant crypt foci and intestinal immune system markers from one hand and tumor occurrence from the other, respectively.


RESULTS
Group A showed a significantly increased metaphase index either in aberrant crypt foci or in "normal appearing" crypts when compared to group A (p < 0.01). Group B rats caused a significant decrease at both sites (p < 0.05). The numbers of lymphocytes derived from the mesenteric lymph nodes in group B rats were significantly decreased (p < 0.01) as compared to either control and to group C. The percentage of CD8 lymphocytes in group C was significantly higher than that in group B. Group C showed a significantly reduced ratio of aberrant crypt foci/colon and of aberrant crypt per colon and per each single focus (p < 0.05). A total of 18 (90%) group B and 10 (50%) group C rats had colon tumors, this difference was significant. The mean number of colon tumors per rat was 2.2 and 1.0 in group B and C, respectively.


CONCLUSIONS
Effective probiotics treatment, through mechanisms still to be fully elucidated (decreased fecal pH, specific reduction of carcinogenetic bacterial enzymes, modulation of gut-associated and systemic immune system etc.) has the potential to exert significant antimutagenic properties against colon cancer.
Marotta
F
F
Hepato-Gastroenterology Unit, Medical Science Department S. Giuseppe Hospital, Traditional Medicine-WHO Center, University of Milan, Milan, Italy. fmarchimede@libero.it
Naito
Y
Y
Minelli
E
E
Tajiri
H
H
Bertuccelli
J
J
Wu
C C
CC
Min
C H
CH
Hotten
P
P
Fesce
E
E
D000818:Animals; D001397:Azoxymethane; D001644:Bifidobacterium; D018414:CD8-Positive T-Lymphocytes / Q000187:drug effects / Q000276:immunology; D002471:Cell Transformation, Neoplastic / Q000187:drug effects* / Q000473:pathology; D003110:Colonic Neoplasms / Q000139:chemically induced / Q000276:immunology / Q000473:pathology*; D007279:Injections, Subcutaneous; D007413:Intestinal Mucosa / Q000187:drug effects / Q000276:immunology / Q000473:pathology; D019266:Iron, Dietary; D007778:Lactobacillus; D007779:Lactobacillus acidophilus; D008198:Lymph Nodes / Q000187:drug effects / Q000473:pathology; D018655:Lymphocyte Count; D008297:Male; D008940:Mitotic Index; D011230:Precancerous Conditions / Q000139:chemically induced / Q000276:immunology / Q000473:pathology*; D019936:Probiotics / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D014815:Vitamins
D019266:Iron, Dietary; D014815:Vitamins; D001397:Azoxymethane