Probiotics and postbiotics in colorectal cancer: Prevention and complementary therapy

Table 3 Efficiency of next-generation probiotics in colorectal cancer in vivo

NGP strain	Application	Study/ cohort	Mechanism/effect(s)	Ref.
Akkermansia muciniphila MucT ATCC BAA-835	pasteurized culture 1.5 × 108 CFU/100 μL or recombinant Amuc_1100 3 μg (specific outer membrane protein)/2 wk before AOM injection until sacrifice	23-wk in vivo animal study, acute colitis was induced by AOM (10 mg/kg) (intraperitoneally) + 2% DSS (in water)-male C57BL/6J mice	Prevention of AOM/DSS-induced tumorigenesis by DNA damage attenuation, cell apoptosis and abnormal proliferation. Significant amelioration of acute colitis, relieved colon shortening and splenomegaly, delayed tumor formation and reduced expression of γH2AX, cleaved caspase 3 and Ki67. Blunted CAC through the expansion and activation of cytotoxic T lymphocytes, indicated by TNF-α induction and PD-1 downregulation	Wang et al[67]
Akkermansia muciniphila ATCC BAA-835	1 × 108 CFU/mouse every other day (day 7-12), gavage administration	4-wk in vivo animal study, CRC induced by mice colon cancer cells CT-26 (1 × 106) (subcutaneously)-n = 70, male BALB/c mice	A. muciniphila colonization significantly increased inhibition rate/anti-cancer effect of FOLFOX (from 48% to 76%) and significantly decreased marker of proliferation-Ki67 (% of positively stained cells)	Hou et al[68]
Clostridium butyricum (powder by Kexing Biopharm CO., LTD)	2 × 108 CFU/0.2 mL/3 times per week, gavage administration	78 d in vivo animal study, CAC induced by intraperitoneal AOM (12.5 mg/kg) + 2.5% DSS (in water)-n = 30, C57BL/6 mice	Inhibition of NF-κB pathway and apoptosis promotion. Change in the microbiome composition-reduction of Firmicutes to Bacteroidetes ratio. Reduction of incidence and size of CRC and increase of tumor cells apoptosis. Reduction in cytokines including TNF-α, IL-6 and level of COX-2. Decrease in phosphorylation of NF-κB and level of Bcl-2. Increase in Bax expression	Liu et al[69]
Clostridium butyricum ATCC 19398 or Bacillus subtilis ATCC 23857	2.5 × 108 CFU/0.3 mL/3 times per week for 28 wk, oral administration	28 wk in vivo animal study. CRC induced with DMH (20 mg/kg body weight)/weekly (intraperitoneally)-n = 72, male C57BL/6 mice	Inhibition of intestinal tumorigenesis and modulation of immunity and inflammation. Reduction in tumor size and incidence. After supplementation with probiotics, mice showed decreased Th2 and Th17 expression and increased CD4/CD8 expression compared to DMH-treated mice. Reduced gene expression of TLR4–MYD88–NF-κB, IL-22 and increase of P21waf1 and Tlr3 mRNA levels in intestinal mucosa	Chen et al[31]

AOM: Azoxymethane; CAC: Colitis-associated cancer; CRC: Colorectal cancer; DMH: 1,2-dimethylhydrazine; DSS: Dextran sulfate sodium; FOLFOX: Oxaliplatin, fluorouracil and calcium folinate; IL: Interleukin; NF-κB: Nuclear factor-kappa B; TNF-α: Tumor necrosis factor-alpha.