The Role of Probiotics in Colorectal Cancer Management

Table 3

Probiotic supplementation and CRC: outcomes of clinical studies on human subjects.

Subjects	Place of study	Intervention	Duration	Key results	References
CRC patients undergoing adjuvant chemotherapy; n = 150 (74 females, 76 males); age = 31 to 75 years	Helsinki University Central Hospital, Finland	Lactobacillus rhamnosus GG (1–2 × 10^10/day) capsules, and guar gum fiber containing nutritional supplement	24 weeks	↑ abdominal comfort level; ↓ stool frequency	[52]
CRC patients undergoing chemotherapy; n = 140; age = 18 years and above	University of Malaya Medical Centre, Malaysia	L. casei, L. acidophilus, L. lactis, B. bifidum, B. longum, B. infantis (30 × 10^9 CFU/sachet; 2 sachets per day) and ω-3 fatty acid (2 g per day)	4 weeks of probiotics and 8 weeks of ω-3 fatty acid	Improved the quality of life and inflammatory status of the CRC patients	[53]
CRC and polypectomized patients; n = 80; age = 40 to 70 years	Mercy University Hospital, Cork, Ireland	L. rhamnosus GG, B. lactis Bb12 (1 × 10^10 CFU of both probiotics in a capsugel), oligofructose-enriched inulin (12 g per sachet per day)	12 weeks	↑ Lactobacillus and Bifidobacterium species; ↓ Clostridium perfringens; ↓ colorectal proliferation; ↑ barrier function and IFN-γ production; ↓ genotoxins exposure and IL-2 secretion	[54]
CRC patients; n = 22 (10 females, 12 males); age = 40 to 75 years, and healthy volunteers; n = 11 (5 females, 6 males); age = 40 to 75 years	Sixth People’s Hospital, Shanghai Jiao Tong University, Shanghai, China	B. longum, L. acidophilus, and Enterococcus faecalis (1 × 10^7 CFU/g; 2 g per capsule; 6 × 10^7 CFU/day)	5 days	↑ density and diversity of mucosal microbiota in CRC patients; ↓ Fusobacterium species in CRC patients	[55]
Human volunteers; n = 380; age = 40 to 65 years	Osaka Medical Centre for Cancer and Cardiovascular Diseases, Osaka, Japan	L. casei strain Shirota (1 × 10^10 CFU/g of powder/after each meal) or wheat bran biscuits (7.5 g wheat bran in 25 g biscuits per day) or both	4 years	The incidence of tumor formation was low in the probiotic group; prevented the atypia of colorectal tumors.	[56]
Healthy human subjects; n = 20 (7 females, 13 males); age = 21 to 75 years		B. lactis (1 × 10^9 CFU/g; 5 g/capsule/day) and/or resistant starch (12.5 g per sachet; 25 g per day)	Each intervention lasts for 4 weeks with no washout period^#	↑ Lachnospiraceae spp. level; No changes in serum biomarkers and epithelial proliferation	[57]
CRC patients; n = 31 (9 females, 22 males); age = 18 to 80 years	Department of Surgery, San Gerardo Hospital, Milano-Bicocca University, Monza, and Department of Surgery, San Raffaele Hospital, Vita e Salute University, Milan, Italy	B. longum and L. johnsonii (2 × 10^7 or 2 × 10^9 CFU per day); the powdered form of probiotics were consumed by mixing in nutritional supplement (100 mL)	3 days before surgery, on the day of surgery, and 2 days after surgery	L. johnsonii was observed in patients’ fecal samples but not B. longum. Adhesion of L. johnsonii was directly correlated with the probiotic dose; ↓ Enterobacteriaceae count in high-dose probiotic group; ↑ CD3, CD4, CD8 and lymphocyte subsets expression; Dendritic cells were not activated and affected	[58]
CRC patients; n = 100 (41 females, 59 males); age = 45 to 75 years	Sixth People’s Hospital, Shanghai Jiao Tong University, Shanghai, China	L. plantarum L. acidophilus B. longum (2 g of encapsulated probiotics containing total 2.6 × 10^14 CFU/day)	6 days before surgery and 10 days after surgery	↑ transepithelial resistance; ↓ lactulose/mannitol ratio; ↓ transmucosal permeability; ↓ bacterial translocation; ↑ tight junction protein expression; ↓ enteropathogenic bacteria load; ↓ incidence of diarrhea and infections	[59]
CRC patients; n = 150 (72 females, 78 males); age = 45 to 75 years	Sixth People’s Hospital, Shanghai Jiao Tong University, Shanghai, and Sixth Affiliated Hospital of Sun Yat-sen University, Guangzhou, China	L. plantarum L. acidophilus B. longum (2 g of encapsulated probiotics containing total 2.6 × 10^14 CFU/day)	6 days before surgery and 10 days after surgery	↓ serum zonulin; ↓ duration of postoperative pyrexia, infection, and antibiotic treatment; ↓ p38 MAPK pathway	[60]
CRC patients; n = 15 (9 females, 6 males); age = 68 to 75 years. Noncancer control group (individuals with normal colonic mucosa); n = 21 (17 females, 4 males); age = 55 to 73 years.		2 tablets containing 1.4 × 10^10 CFU of B. lactis, 7 × 10^9 CFU of L. acidophilus, inulin (630 mg) per day	8–78 days	Improved the diversity and abundance of butyrate-producing bacteria (Clostridiales and Faecalibacterium species) in fecal and mucosal microbiota of CRC patients; Significant reduction of Fusobacterium and Peptostreptococcus species in fecal microbiota of CRC patients	[61]
CRC survivors^##; n = 60 (25 females, 35 males); age = 45 to 70 years	Clinical Trial Centre in Severance hospital, Yonsei University, Republic of Korea	L. rhamnosus R0011, and L. acidophilus R0052 (2 × 10^9 CFU/tablet, twice a day)	12 weeks	↓ irritable bowel symptoms; Improved the overall quality of the life	[62]
CRC patients; n = 156 (65 females, 91 males); age = 45 to 75 years	Fukuoka University Hospital, Fukuoka, Japan	BIO-THREE®(2 mg of E. faecalis T110, 10 mg of Clostridium butyricum TO-A, and 10 mg of Bacillus mesentericus TO-A per tablet); 6 tablets per day	3–15 days before surgery	↓ superficial incisional surgical site infections; Improved the microbiota	[63]
CRC patients; n = 40 (16 females, 24 males); age = 45 to 80 years		L. acidophilus, L. casei, L. lactis, B. infantis. B. bifidum, and B. longum (30 × 10^9 CFU/sachet; twice per day)	7 days before surgery	Improved the gut function, and reduced the duration of hospital stay after surgery	[64]
CRC patients; n = 60 (33 females, 27 males); age = 45 to 80 years	Sixth People’s Hospital, Shanghai Jiao Tong University, Shanghai, China	Probiotic powder containing B. longum (1 × 10^7 CFU/g), L. acidophilus (1 × 10^7 CFU/g) and E. faecalis (1 × 10^7 CFU/g)	5 days before surgery and 7 days after surgery	Improved the bowel function; ↓ incidence of diarrhea	[65]
CRC patients; n = 164 (49 females, 115 males); age = 45 to 80 years	Department of Surgery of the AHEPA University Hospital of Thessaloniki, Greece	1.75 × 10^9 CFU of B. lactis BB-12, 1.75 × 10^9 CFU of L. acidophilus LA-5, 0.5 × 10^9 CFU of L. plantarum, and 1.5 × 10^9 CFU of S. boulardii per capsule; twice per day	16 days (1 day before surgery and 15 days after surgery) and 30 days of follow-up period	↓ anastomotic leakage, pneumonia, and infection in surgical site.; Altered the expression of IL-6, TNF, and SOCS3	[70]
CRC patients; n = 75 (32 females, 43 males); age = 60 to 75 years	First Department of Propaedeutic Surgery of Athens Medical School at Hippocration Hospital, Athens, Greece	Each 12 g of synbiotic sachet contains probiotics (Pediococcus pentosaceus, Leuconostoc mesenteroides, L. paracasei, L. plantarum; each 10 × 10^11 CFU) and prebiotics (inulin, resistant starch, pectin, and b-glucan; each 2.5 g); 1 sachet per day	15 days	↑ gastrointestinal Quality of Life Index; Improved the functional bowel disorder score	[71]

↑: increased; ↓: decreased; IFN-γ: interferon-γ; IL-2: interleukin-2; IL-6: interleukin-6; CRC: colorectal cancer; p38 MAPK: p38 mitogen-activated protein kinase; TNF: tumor necrosis factor; SOCS3: suppressor of cytokine signaling 3. Patients who had surgical elimination of at least 2 colorectal tumors; Patients undergoing colorectal surgery; ^#Intervention of probiotic, prebiotics, and synbiotics in a sequential way, and each intervention last for 4 weeks;^##CRC patients those who have completed their treatment for the disease.