Table 2.
Effect of probiotic supplementation in CRC experimental animals.
| Experimental model | Intervention | Duration of treatment | Key results | References |
|---|---|---|---|---|
| ApcMin/+ CRC mouse model | L. acidophilus ATCC 314, L. fermentum NCIMB 5221 (each 0.5 × 1010 CFU; total 1 × 1010 CFU/day) | 12 weeks | ↓ multiplicity of tumors ↓ β-catenin and Ki-67 |
[29] |
|
| ||||
| Azoxymethane-mediated colonic neoplasm induced Sprague-Dawley rats | B. lactis (1 × 1011 CFU/g), and/or resistant starch (∗Hi-maize® 958 or Hi-maize® 260; 100 g/kg diet) | ∼22 weeks | ↓ incidence and development of colonic neoplasms The protective effects were observed to be higher in the synbiotic supplemented group |
[33] |
|
| ||||
| Trinitrobenzene sulfonic acid-mediated chronic colitis induced Sprague-Dawley rats | VSL#3 (B. breve, B. infantis, B. longum, L. acidophilus, L. bulgaricus, L. casei, L. plantarum, and Streptococcus salivarius subsp. thermophilus), 5 × 109 CFU/100 g of body weight | Differs∗∗ | No carcinoma development No high-grade dysplasia ↓ colon damage ↑ expression of antiangiogenic factor angiostatin, alkaline sphingomyelinase, and vitamin D receptor. |
[34] |
|
| ||||
| Azoxymethane/dextran sodium sulfate-mediated colitis-associated CRC induced mouse model | VSL#3 (1.3 × 106 CFU/day), and/or Balsalazide (300 mg/kg body weight/day) | 2 weeks before azoxymethane exposure and continued for 9 weeks until sacrification | ↓ number of tumors ↓ F4/80-positive macrophages ↓ p-STAT3 expression ↓ BCL-2 expression ↓ MIP-1β, MCP-1, IL-6, IL-10 level ↑ BAX expression |
[35] |
|
| ||||
| Azoxymethane-mediated colitis-associated CRC induced mouse model | VSL#3 (1 × 109 CFU/day) | 19 weeks (from 6th week to 24th week) | ↓ Clostridium species No reduction in tumorigenesis |
[36] |
|
| ||||
| 1,2-Dimethyl hydrazine (DMH)-mediated CRC induced Sprague Dawley rats | L. rhamnosus GG, or L. casei, L. plantarum, or L. acidophilus, or B. bifidum. (probiotic dose: 1 × 109 CFU/day) | Seven weeks (1 week before starting DMH exposure and continued for 6 weeks) | ↓ percentage of Aberrant crypt foci (ACF) ↓ nitroreductase activity, β-glucuronidase activity, β-glucosidase activity |
[37] |
|
| ||||
| DMH-mediated CRC-induced Sprague Dawley rats | Synbiotic (L. rhamnosus GG, L. acidophilus, and inulin; 1 × 109 CFU probiotic +5 mg inulin/day) or probiotic (L. rhamnosus GG, and/or L. acidophilus; 1 × 109 CFU probiotic/day) or prebiotic (inulin; 5 mg/day) | 19 weeks (1 week before starting DMH exposure and continued for 18 weeks) | ↓ MDA level ↑ GSH, SOD, and GPx Improved the histopathological score |
[38] |
|
| ||||
| DMH-mediated CRC-induced rats | L. acidophilus LaVK2 and B. bifidum BbVK3 or both probiotic + piroxicam; 2 × 109 CFU/g of each probiotic | 32 weeks | ↓ number of ACF, mucin-depleted foci, and proliferating cell nuclear antigen | [39] |
|
| ||||
| DMH-mediated CRC-induced rats | L. plantarum AS1 (1 × 109 CFU/day) | 5–21 weeks | ↑ antioxidant system of the host ↓ tumor diameter and number of tumors |
[40] |
|
| ||||
| DMH-mediated CRC-induced rats | L. salivarius (5 × 108 or 1 × 1010 CFU/kg body weight/day) | 15 weeks (2 week before starting DMH exposure and continued until 15 weeks) | Improved the colonic microflora and luminal metabolisms. ↓ number and multiplicity of ACF, azoreductase activity ↑ short-chain fatty acid levels |
[41] |
|
| ||||
| CT26 tumor-bearing mice | L. plantarum or L. rhamnosus; 1 × 109 CFU/day | Pre-exposure for 14 days | ↓ CT26 growth ↑ lifespan of tumor-bearing mice ↑ IFN-γ, Th1-type CD4+ T differentiation ↑ CD8+ function ↑ NK cell infiltration |
[42] |
|
| ||||
| DMH-mediated CRC-induced rats | L. salivarius Ren (5 × 1010 CFU/kg body weight/day) | 32 weeks | Reversed the DMH-induced altered microbiota | [43] |
| DMH-mediated CRC-induced rats | L. rhamnosus GG CGMCC 1.2134 (1 × 109 CFU/day) | 25 weeks | ↓ incidence, multiplicity, and volume of tumor ↓expression of inflammatory proteins, and antiapoptotic protein ↑ proapoptotic proteins |
[44] |
|
| ||||
| DMH-mediated CRC-induced mice | L. casei BL23 (10 µl; 1 × 108 CFU/µl) | 3 days (on days 0, 14, 28) | ↓ incidence of tumor ↓ multiple plaque lesions Regulates the Treg and Th17 T cells Altered the expression of IL-6, IL-10, IL-17, and TGF-β |
[45] |
|
| ||||
| DMH and SW480 cell-mediated CRC-induced rat | B. infantis (1 × 109 CFU/day) and/or 5-FU + oxaliplatin | 11 days | ↑ body weight and intestinal villus height ↓ IL-6, IL-1β, TNF-α levels, and Th17 and Th1 cell-associated cytokines ↑ CD4+, CD25+, Foxp3+, Tregs expressions |
[46] |
|
| ||||
| Azoxymethane/dextran sodium sulfate-mediated colitis-associated cancer-induced mice model | B. longum, L. acidophilus, and E. faecalis (1.2 × 107 CFU/day) | Pretreatment for 2 weeks and continued till the end of the experiment | ↓ intestinal inflammation and tumor formation. ↓ Desulfovibrio, Mucispirillum, and Odoribacter species ↑ Lactobacillus species Altered the expression of CXCR2 ligand genes |
[47] |
|
| ||||
| Azoxymethane-mediated CRC-induced mice | L. acidophilus (1 × 109 CFU/day) and B. bifidum (1 × 109 CFU/day) | 5 months | ↓ miR-135b, miR-155, and KRAS ↑ miR-26b, miR-18a, APC, PU.1, and PTEN | [48] |
|
| ||||
| Azoxymethane/dextran sodium sulfate-mediated CRC-induced rat model | L. acidophilus LA5 and/or B. animalis subsp. Lactis BB-12, and GBR; 5 × 107 CFU of single probiotic strain/day or 2.5 × 107 CFU each strain/day | 10 weeks | ↓ mucin-depleted foci formation ↑ expression of p53, Bax, caspase-3, and Bax/Bcl-2 ratio ↓ Bcl-2 expression ↑ SOD activity ↓ aberrant crypt foci (ACF)-producing sialomucin |
[49] |
|
| ||||
| DMH-mediated CRC-induced rats | L. rhamnosus GG MTCC #1408, and/or L. acidophilus NCDC #15 (1 × 109 CFU/day), and/or celecoxib (6 mg/kg body weight) | 18 weeks | ↓ multiplicity and tumor burden ↓ Bcl-2, K-ras expression ↑ Bax, p53 expression |
[50] |
|
| ||||
| DMH-mediated CRC-induced rats | L. rhamnosus GG MTCC #1408, and/or L. acidophilus NCDC #15 (1 × 109 CFU/day), and/or celecoxib (6 mg/kg body weight) | 6 weeks | ↓ ACF formation ↓ β-catenin, COX-2, and NF-κB expression |
[51] |
↑: increased; ↓: decreased; MDA: malondialdehyde; GSH: glutathione; SOD: superoxide dismutase; GPx: glutathione peroxidase; NK: natural killer; IFN-γ: interferon-γ; p-STAT3: phospho-signal transducer and activator of transcription 3; BCL-2: B-cell lymphoma 2; BAX: BCL2-associated X protein; MIP-1β: macrophage inflammatory protein 1 beta; MCP-1: monocyte chemoattractant protein-1; IL-6: interleukin-6; IL-10: interleukin-10; KRAS: Kirsten rat sarcoma 2 viral oncogene homolog; GBR: germinated brown rice; ∗Hi-maize® (high-amylose maize starch was used as a source of resistant starch); ∗∗From one week before colitis induction to death of the experimental animal.