British Journal of Nutrition

Full Papers

Increased induction of apoptosis by Propionibacterium freudenreichii TL133 in colonic mucosal crypts of human microbiota-associated rats treated with 1,2-dimethylhydrazine

Annaïg Lana1a2, Aurélia Bruneaua3, Martine Bensaadaa3, Catherine Philippea3, Pascale Bellauda4, Sylvie Rabota3 and Gwénaël Jana1 c1

a1 INRA, Agrocampus Rennes, UMR1253 Science et Technologie du Lait et de l'Oeuf, Rennes F-35000, France

a2 Laboratoires Standa, Caen F-14050, France

a3 INRA, UR910 Ecologie et Physiologie du Système Digestif, Jouy-en-Josas F-78350, France

a4 Laboratoire d'Anatomie Pathologique, Faculté de Médecine, Université de Rennes 1, Rennes F-35000, France


Propionibacterium freudenreichii, a food-grade bacterium able to kill colon cancer cell lines in vitro by apoptosis, may exert an anticarcinogenic effect in vivo. To assess this hypothesis, we administered daily 2 × 1010 colony-forming units (CFU) of P. freudenreichii TL133 to human microbiota-associated (HMA) rats for 18 d. Either saline or 1,2-dimethylhydrazine (DMH) was also administered on days 13 and 17 and rats were killed on day 19. The levels of apoptosis and proliferation in the mid and distal colon were assessed by terminal deoxynucleotide transferase-mediated deoxyuridine triphosphate nick end labelling (TUNEL) and proliferating cell nuclear antigen (PCNA) immunolabelling, respectively. The administration of P. freudenreichii TL133 significantly increased the number of apoptotic cells in DMH-treated rats compared to those given DMH only (P < 0·01). Furthermore, propionibacteria were able to decrease the proliferation index in the distal colon after treatment with DMH (P < 0·01). Conversely, propionibacteria alone did not exert such an effect on healthy colonic mucosa. P. freudenreichii TL133 thus facilitated the elimination of damaged cells by apoptosis in the rat colon after genotoxic insult and may play a protective role against colon cancer.

(Received November 13 2007)

(Revised March 10 2008)

(Accepted March 11 2008)

(Online publication May 09 2008)


c1 Corresponding author: Dr Gwénaël Jan, fax +33 2 23 48 53 50, email


Abbreviations: CFU, colony-forming units; DMH, 1,2-dimethylhydrazine; HMA, human microbiota-associated; PAB, propionic acid bacteria/propionibacteria; PCNA, proliferating cell nuclear antigen; TUNEL, terminal deoxynucleotide transferase-mediated deoxyuridine triphosphate nick end labelling