Lactobacillus gasseri TMC0356 (TMC0356), a probiotic strain originally isolated from the human intestine, was tested for its anti-tumor activities in vivo in murine tumor models. Oral administration of TMC0356 characteristically inhibited the growth of sarcoma S-180 (S-180) and hepatoma H22 (H22) cells, which had been implanted in mice. Serum gamma interferon was significantly enhanced during TMC0356 administration of 1,000 mg/kg in S-180-bearing mice (p<0.01). Serum levels of tumor necrosis factor- α and interleukin-18 were also altered, though these changes were not statistically significant. These results indicate that the anti-tumor effects of TMC0356 might, at least in part, arise from the impact of this bacterium on cell-mediated immunity in host animals.
We examined the immunomodulation capability of Bifidobacterium longum strains via a Transwell co-culture system using human colonic epithelial cells, Caco-2, in the upper chamber, and human macrophage-like cells, THP1, in the lower chamber of the culture. Heat-treated cells of three B. longum strains, JCM1217T, KT237 or H7-115, were added to the upper chamber to allow direct contact with Caco-2 cells and the culture was incubated for 24 hr. After incubation, THP-1 cells in the lower chamber were placed in a separate well containing fresh medium with LPS and incubated for 6 hr. After incubation, we found that TNF-α secretion from THP-1 cells, that had been co-cultured with Caco-2 directly contacting heat-treated cells of B. longum strains, especially H7-115, was suppressed. This was, however, not the case in an the almost identical experiment using B. longum cells killed under ultra-violet light (not heat-treated). We then blocked Caco-2 TLR2 with anti-TLR 2 antibodies in another co-culture experiment and found that blocking TLR2 canceled the indirect anti-inflammatory effect of B. longum H7-115. The evidence suggests that some heat-resistant somatic structures of B. longum can modulate a host's immune response at least via TLR2 expressed on intestinal epithelial cells.