Table 2.
Summary of reviewed studies on the relationship probiotics and mucositis in cancer patients.
| Author, Year | Design | Country | Patients | Pathology | Monitoring | Intervention | Results |
|---|---|---|---|---|---|---|---|
| Jiang 2008 [20] |
Randomized, double-blind, placebo-controlled trial monocentric | China | 99 M/F = 58/35 Median age = 51 years | Advanced NC and undergoing CCRT |
seven weeks | CCRT and B.longum, L.lactis, E.faecium. (six capsules/day) OM incidence, the short-term curative effect, the immune index, and fecal flora changes. | Probiotic combination reduced the incidence of grade 3 OM and had significantly enhanced the immunity of patients and was beneficial for restoring microbial diversity after the end of CCRT. |
| Gao 2015 [21] |
Randomized prospective placebo-controlled trial. | China | 22 M/F = 12/10 Median age = 70 years |
CRC | five days perioperative surgery | B.longum L.acidophyllus, Efaecalis (1:1:1). 6 × 107 CFU/day. Oral probiotics were able to alter the microbial composition and improve gut microbiota in patients with CRC. | Probiotic supplements can effectively alter the composition, richness, and diversity of the gut microbiota |
| Liu 2010 [22] |
Randomized, double-blind, placebo-controlled, prospective trial | China | 100 M/F = 59/41 Median age = 65 years |
CRC | 16 days (six days pre-and 10 days post-operative) | L.acidophillus, L.plantarum, B.longum (1 × 1014 CFU/day). Preoperative administration could prevent post-operative alterations in intestinal permeability, integrity and microbiota. | Probiotics can improve the integrity of the gut mucosal barrier and balance of the gut microbiota, and they play a role in decreasing the infectious rate. |
| Gianotti 2010 [23] |
Prospective, randomized, double-blind, clinical trial | Italia | 31 M/F = 22/11 Median age = 64 years |
CRC | six days (three pre- and three post-operative) | B.longum and L.johnsonii (2 × 107 and 2 × 109 CFU/day). Assess adhesion to the colonic mucosa, reduce concentration of pathogens in stools, and modulate local immune function. | L.johnsonii but not B.longum, adhere to the colonic mucosa, affect intestinal microbiota by reducing the concentration of pathogens, and modulate local immunity. |
| Worthley 2009 [24] |
Randomized, double-blind, placebo-controlled crossover trial | Australian | 20 M/F = 13/7 Median age = 65.5 years |
Healthy | 16 weeks | (B.animalis sub.lactis 5 × 109 CFU/day + 25 g/day HAMS), Synbiotic. Characterized the luminal and biological consequences of these supplements and placed them in the context of colorectal carcinogenesis. | Synbiotic generated a significantly different fecal bacteria profile when compared with either HAMS or B.animalis sub.lactis supplementation alone. |
| Friederich 2011 [25] |
Randomized pilot study | Netherlands | 31 M/F = 20/11 Median age = 37 years |
FAP and IPAA | six weeks | Sulindac (300 mg/day), VSL#3 (9 × 1011 CFU/day) + Inulin (12g/day). Endpoints: Risk parameters cell proliferation and GST detoxification capacity in the pouch mucosa. SCFA contents, pH, and cytotoxicity of fecal water. | Study revealed non-significant decreased cell proliferation and increased detoxification capacity after treatment with sulindac or VSL#3/inulin (prebiotic). |
| Lacouture 2016 [26] |
Multicenter, double cohort placebo-controlled randomized phase II trial | USA and Republic. of Korea | 173 M/F = 98/75 Median age = 66 years | Advanced NSCLC | four to eight weeks according to treatment | Dacomitinib all cohorts Cohort I: Doxycycline + placebo. Cohort II: AD+ VSL#3. Cohorts I and II assessment incidence of all grade and grade ≥ 2 SDAEI and QoL. Cohort II assessment incidence of all grade and grade ≥ 2 diarrhea and mucositis | Doxycycline was effective as a prophylactic treatment for dacomitinib-induced grade ≥ 2 SDAEI. Both doxycycline and AD reduced the negative impact in patient-reported dermatologic AEs. The probiotic was not effective for preventing diarrhea or mucositis |
| Hegazy 2010 [27] |
Multicenter, placebo-controlled randomized | Egypt | 40 M/F = 29/11 Median age = 47 years | UC | eight weeks | L.delbruekii and L.fermentum 1 × 1010 CFU/day. Effect in patients with ulcerative colitis (UC), and their effect on inflammatory mediators and NF-κB activation | Oral supplementation with probiotics could be helpful in maintaining remission and preventing relapse of UC |
| Groeger 2013 [28] |
Randomized, double-blind, placebo-controlled | Ireland | 118 M and F = 48 (UC and Psoriasis) F = 83 (CFS and healthy) |
UC. Psoriasis. CFS. Healthy. | six - eight weeks | B. infantis strain 35,624 1 × 1010 CFU/day Assessed the impact on inflammatory biomarker and plasma cytokine levels in UC, CFS, and psoriasis | B.infantis strain 35,624, was enough to reduce systemic inflammatory biomarkers in both gastrointestinal and extra-intestinal inflammatory disorders. |
| Sharma 2012 [29] |
Randomized, double-blind, single center, placebo controlled | India | 200 M/F = 188/12 Median age = 51 years | HNSCC stage II–IVA | 25 months | L.brevis strain CD2 2 × 109 efficacy in preventing oral mucositis in patients receiving CRT for HNSCC. | L.brevis strain CD2 proved to be safe and efficacious in reducing the incidence of severe oral mucositis in patients with HNSCC undergoing combination radiation and chemotherapy |
| D Sanctis 2019 [30] |
Multicentric, phase III, open label, randomized controlled | Italy | 68 M/F = 53/15 Median age = 60 years | HNC | 39 months | L.brevis strain CD2 2 × 109 primary endpoint was the incidence of grade 3 or 4 oropharyngeal mucositis during radiotherapy treatment | L.brevis strain CD2 not able to confirm the beneficial effects in reducing the rate of grade 3–4 RT-induced OM in patients with HNC. |
| Consoli 2015 [31] |
Randomized controlled | Brazil | 33 M/F = 15/18 Median age = 55 years | RC | seven days before surgery and was interrupted on the operation day. | S.boulardii 0.5 × 109 CFU to assess the role of preoperative treatment on mRNA levels for immunomodulatory cytokines in the colonic mucosa of patients. | S.boulardii downregulates both pro- and anti-inflammatory cytokines in the intestinal colonic mucosa with no statistical impact on postoperative infection rates. |
| Wada 2009 [32] |
Randomized, placebo-controlled single-blinded | Japan | 40 M/F = 16/24Median age = 6.5 years | IC | one to five weeks | B.breve strain Yakult 109 CFU, on its ability to prevent infection, fecal micro flora, and intestinal environments in cancer patients on chemotherapy. | B.breve strain Yakult could be an effective approach for achieving clinical benefits in immunocompromised hosts by improving their intestinal environments (mucositis, fever, diarrhea and bacteremia). |
| Mangell 2012 [33] |
Randomized double-blinded, placebo-controlled | Sweden | 64 M/F = 36/28Median age = 72 years | RC | six months | L.plantarum strain 299v 1011 CFU on the intestinal load of potentially pathogenic bacteria, bacterial translocation, and cell proliferation in elective colon surgery. | L.plantarum strain 299v was established in the intestine, but no inhibitory effect on enteric bacteria, bacterial translocation, or postoperative complications was found |
| Ouwehan. 2008 [34] |
Randomized double-blinded, placebo-controlled | Finland | 47 M/F = 12/35Median age = 71 years | Healthy and regular use of NSAID | six weeks | Synbiotic (lactitol + 2 × 109 CFU L.acidophyllus strain NCFM) on improve bowel function and immune function. | Synbiotic twice daily was associated with modest improvement in stool frequency without any side-effects and improved microbiota composition and mucosal. |
M/F: Number males and females. NC: Nasopharyngeal Carcinoma. CCRT: Concurrent Chemoradiotherapy. OM: Oral mucositis. CRC: Colorectal cancer. B: Bifidobacterium. L: Lactobacillus. E: Enterobacteria. CFU: Colony-forming units. HMAS (prebiotic): High-Amylose Maize Starch. FAP: Familial adenomatous polyposis. IPAA: Ileal pouch anal anastomosis. Sulindac: Non-steroidal anti-inflammatory drug. VSL#3: Mix probiotic. SCFA: Short chain fatty acid. GST: Glutathione S-transferase. NSCLC: Non-small cell lung cancer. QoL: Quality of life. SDAEI: Select dermatologic adverse events of interest. AD: Alclometasone dipropionate. Dacomitinib: Inhibitor of the human epidermal growth factor receptor (HER). AEs: Adverse events. Doxycycline: Broad-spectrum antibiotic. UC: Ulcerative colitis. CFS: Chronic fatigue syndrome. HNSCC: Head and neck squamous cell carcinoma CRT: Chemo-radiotherapy. HNC: Head and neck carcinoma. RT: Radiation therapy. NF κB: Nuclear factor kappa-light-chain-enhancer of activated B cells. mRNA: Messenger RNA. RC: Resection colon. IC: Immunocompromised. NSAID: Non-steroidal anti-inflammatory. S: Saccharomyces. Lactitol (prebiotic): Disaccharide.