Probiotics and postbiotics in colorectal cancer: Prevention and complementary therapy

Table 2 Efficiency of probiotics in colorectal cancer prevention and therapy-clinical trials

Probiotic strain/synbiotics	Dose/length of the study	Trial type/sample size	Microbial changes/key outcomes	Ref.
Lactobacillus rhamnosus GG, Bifidobacterium lactis Bb12 + inulin enriched with oligofructose	1010 CFU and 10 g of prebiotic, 12 wk	Human prevention study-CRC patients (n = 15 placebo, n = 19 synbiotics), polypectomized patients (n =19 placebo, n = 21 synbiotics)	↑Bifidobacterium, ↑Lactobacillus, ↓Clostridium perfringens; ↓proliferation rate of colorectal cells and stimulation of peripheral blood mononuclear cells (↑IFNg, ↓IL-2)	Rafter et al[58]
Bifidobacterium longum BB536, Lactobacillus johnsonii La1	2 × 107 CFU or 2 × 109 CFU, 3 d preoperatively and 3 d postoperatively	CRC patients undergoing elective colorectal resection- Randomized double blind, placebo-controlled study (n = 10 placebo, n = 21 probiotics)	B. longum BB536 did not adhere to colonic mucosa only La1, ↓Enterobacteriaceae ↓Enterococcus, modulation of local immunity (↑CD3+, CD4+, CD8+, activity of dendritic cells); no clinical effect	Gianotti et al[59]
Bifidobacterium longum, Lactobacillus acidophilus, Enterococcus faecalis	3 × 108 CFU, 3 d (from -5 to -3 d) preoperatively	Single-center prospective randomized control study (n = 30 placebo, n = 30 probiotics)	↑Bifidobacterium and ↓Escherichia; ↓endotoxins, D-lactic acid, serum IL-6 and C-reactive protein; ↑serum IgG and IgA; ↓postoperative occurrence of infectious complications of CRC	Zhang et al[60]
Bifidobacterium longum, Lactobacillus acidophilus and Enterococcus faecalis	1:1:1 daily 6 × 107 CFU, 5 d	Perioperative intake of probiotics in CRC patients (n = 11 placebo, n = 11 probiotics)	↑richness and diversity of mucosal microbes, ↓Peptostreptococcus, ↓Comamonas, ↓Fusobacterium, ↑Enterococcus, ↑Proteobacteria; no clinical effect	Gao et al[61]
LactoLevure (Lactobacillus acidophilus LA-5, Lacobacillus plantarum, Bifidobacterium lactis BB-12, Saccharomyces boulardii)	1.75 × 109 CFU, 0.5 × 109 CFU, 1.75 × 109 CFU, 1.5 × 109 CFU, respectively, 1 d preoperatively and 15 d postoperatively	CRC patients undergoing surgery- Randomized, double-blind, placebo-controlled study (n = 80 placebo, n = 84 probiotics)	Reduction of the postoperative pneumonia rate, anastomotic leakage and surgical site infections; ↑gene expression of SOCS3; ↑circulating IL-6, TNF-α	Kotzampassi et al[62] (NCT02313519)
Colon DophilusTM [Bifidobacterium breve HA-129 (25%), Bifidobacterium bifidum HA-132 HA (20%), Bifidobacterium longum HA-135 (14.5%), Lactobacillus rhamnosus HA-111 (8%), Lactobacillus acidophilus HA-122 (8%), Lactobacillus casei HA-108 (8%), Lactobacillus plantarum HA-119 (8%), Streptococcus thermopilus HA-110 (6%), Lactobacillus brevis HA-112 (2%), Bifidobacterium infantis HA-116 (0.5%)]	10 × 109CFU/ daily, 12 wk	Patients with CRC, concomitantly with irinotecan chemotherapy- Randomized, placebo-controlled study (n = 23 placebo, n = 23 probiotics)	Reduction in the incidence and severity of chemotherapy induced diarrhea and incidence of enterocolitis.	Mego et al[63] (NCT01410955)
Saccharomyces boulardii	7 d preoperatively	Randomized study (n = 18 conventional treatment, n = 15 probiotics)	↓mucosal IL-1β, IL-10, and IL-23A mRNA levels; no statistical impact on postoperative infection rates	Consoli et al[64]
ProBion Clinica (Bifidobacterium lactis Bl-04 and Lactobacillus acidophilus NCFM + inulin)	1.4 × 1010 CFU, 7 × 109 CFU and 0.63 g of prebiotic, 8-78 d	Prospective randomized intervention (n = 7 placebo, n = 8 probiotics)	Increased abundance of butyrate producing bacteria ↑Firmicutes, ↑Faecalibacterium, ↑Eubacterium, ↑Roseburia ↑Lachnospira; ↓CRC associated bacteria- Fusobacterium and Peptostreptococcus	Hibberd et al[65](NCT03072641)
Simbio-flora (Lactobacillus acidophilus NCFM, Lactobacillus rhamnosus HN001, Lactobacillus casei LPC-37, Bifidobacterium lactis HN019 and fructooligosaccharide)	109 CFU and 6 g of prebiotic, 7 d preoperatively	Patients with CRC subjected to colorectal resection- Prospective, randomized, double-blind, placebo-controlled study (n = 37 placebo, n = 36 synbiotic)	Reduced inflammatory state (C-reactive protein, IL-6), reductions in morbidity, hospital length of stay, and use of antibiotics. Stimulated bowel function, decreased complications and reduced cumulative duration of antibiotic usage	Polakowski et al[66]
Lactobacillus acidophilus BCMC® 12,130, Lactobacillus lactis BCMC® 12,451, Lactobacillus casei subsp BCMC® 12,313, Bifidobacterium longum BCMC® 02120, Bifidobacterium bifidum BCMC® 02290 and Bifidobacterium infantis BCMC® 02129	30 billion CFU, twice daily for 6 mo	Randomized double-blind placebo-controlled trial (n = 25 placebo, n = 27 probiotics)	Reduction in the levels of pro-inflammatory cytokines, TNF-α, IL-6, IL-10, IL-12, IL-17A, IL-17C and IL-22.	Zaharuddin et al[32] (NCT03782428)

CRC: Colorectal cancer; IFNg: Interferon-gamma; Ig: Immunoglobulin; IL: Interleukin; TNF-α: Tumor necrosis factor-alpha.