Double blind, placebo controlled trial of two probiotic strains in interleukin 10 knockout mice and mechanistic link with cytokine balance.
BACKGROUND
Prophylactic efficacy against colitis following lactobacillus consumption in interleukin 10 (IL-10) knockout (KO) mice has been reported. Whether this applies equally to other probiotic strains is unknown, and the mechanism is unclear.


OBJECTIVE
(1) To compare the effect of feeding Lactobacillus salivarius subspecies salivarius 433118 and Bifidobacterium infantis 35624 against placebo on enterocolitis, the intestinal microflora, and (2) to compare the systemic immunological response to in vitro microbial challenge in probiotic fed and control IL-10 KO mice.


METHODS
Three groups of 10 IL-10 KO mice were fed fermented milk products containing Lb salivarius 433118 at 10(9) CFU/ml, B infantis 35624 at 10(8) CFU/ml, and unmodified milk, respectively, for 19 weeks. Faecal samples were taken at regular intervals to confirm gut transit, recovery of fed probiotics, and to assess the impact on the microflora. At sacrifice, the bowels were histologically scored. Cytokine production from Peyers' patches and splenocytes was measured in vitro by ELISA.


RESULTS
Faecal recovery of probiotics was confirmed in all probiotic fed mice but not in controls. Colonic and caecal inflammatory scores were significantly decreased in both groups of probiotic fed mice (p<0.05). Proinflammatory cytokine production by Peyers' patches and splenocytes was significantly reduced in probiotic fed animals whereas transforming growth factor beta (TGF-beta) levels were maintained.


CONCLUSIONS
Both Lactobacillus salivarius 433118 and Bifidobacterium infantis 35624 significantly attenuate colitis in this murine model. Attenuation of colitis is associated with a reduced ability to produce Th1-type cytokines systemically and mucosally, while levels of TGF-beta are maintained.
McCarthy
J
J
Department of Medicine, University College Cork, National University of Ireland, Cork, Ireland.
O'Mahony
L
L
O'Callaghan
L
L
Sheil
B
B
Vaughan
E E
EE
Fitzsimons
N
N
Fitzgibbon
J
J
O'Sullivan
G C
GC
Kiely
B
B
Collins
J K
JK
Shanahan
F
F
D000818:Animals; D001644:Bifidobacterium / Q000302:isolation & purification; D015169:Colony Count, Microbial; D003424:Crohn Disease / Q000382:microbiology* / Q000517:prevention & control; D016207:Cytokines / Q000096:biosynthesis; D004195:Disease Models, Animal; D004311:Double-Blind Method; D004797:Enzyme-Linked Immunosorbent Assay; D005243:Feces / Q000382:microbiology; D005260:Female; D005772:Gastrointestinal Transit / Q000502:physiology; D016753:Interleukin-10 / Q000235:genetics; D007422:Intestines / Q000382:microbiology; D007778:Lactobacillus / Q000302:isolation & purification; D051379:Mice; D018345:Mice, Knockout; D008892:Milk; D010581:Peyer's Patches / Q000378:metabolism; D019936:Probiotics / Q000627:therapeutic use*; D011897:Random Allocation; D013154:Spleen / Q000378:metabolism
D016207:Cytokines; D016753:Interleukin-10