Chronic
inflammation is a risk factor for
colorectal cancer, and inflammatory
cytokines secreted from inflammatory cells and
active oxygen facilitate
tumorigenesis. Intestinal bacteria are thought to regulate
tumorigenesis. The longer the breastfeeding period, the lower is the risk of
inflammatory bowel disease. Here, we investigated preventive effects of the probiotic Lactobacillus rhamnosus M9 (Probio-M9) on
colitis-associated
tumorigenesis. An inflammatory
colorectal tumor model was established using a 6-week-old male C57BL/6NCrSlc mouse, which was intraperitoneally administered with
azoxymethane (AOM: 12 mg/kg
body weight). On weeks 2 and 4, 2%
dextran sulfate sodium (DSS) was administered to mice for 7 days through
drinking water. On weeks 8 and 10, Probio-M9 (2 × 109/day) was orally administered for 7 days. Animals were sacrificed at 20 weeks after AOM administration and immunohistochemical staining and Western blotting was performed. The α-diversity of microflora (Shannon index), principal coordinate analysis, and distribution of intestinal bacterium genera and metabolic pathways were compared. The AOM/DSS group showed
weight loss,
diarrhea, intestinal shortening, increased number of colon
tumors, proliferating
tumorigenesis, increased
inflammation score,
fibrosis, increased CD68+, or CD163+ macrophage cells in the subserosal layer of non-
tumor areas.
Inflammation and
tumorigenesis ameliorated after Probio-M9 treatment. Fecal microbial functions were altered by AOM/DSS treatment. Probio-M9 significantly upregulated the fecal microbial diversity and reversed fecal microbial functions. Thus, Probio-M9 could suppress
tumor formation in the large intestine by regulating the intestinal environment and ameliorating
inflammation, suggesting its therapeutic potential for treatment of
inflammation and
colitis-associated
tumorigenesis.