Table 1.

Characteristics of Included Studies.

Reference	Sample	Study design	Intervention	Measures	Key findings and conclusions
De Loera-Rodriguez et al, 37 Mexico	70 patients with cervical cancer, on pelvic radiotherapy and chemotherapy, mean age 49 years, 100% female	Randomized, double-blind controlled trial	Treatment: Synbiotic biogel with 1 × 107 CFU/g Lactobacillus acidophilus NCFM, Bifidobacterium lactis Bi-07, 1 × 106 CFU/g biogel, and blue agave inulin 3× daily, or placebo Duration: 7 weeks	(i) Bristol stool form scale (BSFS) (ii) National Institute of Cancerology (INC) of the United States scale for nausea and vomiting	• Significant decrease in vomiting frequency and intensity in treatment group vs controls (P < .001). • No significant effects on stool consistency or nausea. • In patients with cervical cancer, synbiotic treatment significantly decreased vomiting frequency and intensity.
Demers et al, 38 Canada	229 patients with prostate, endometrial, cervical, or rectal cancer, on pelvic radiotherapy treatment, mean age 61 years, 96.7% male	Randomized, double-blind controlled trial	Treatment: Probiotic “Bifilact” Lactobacillus acidophilus LAC-361 and Bifidobacterium longum BB-536 at doses of either (i) 1.3 billion CFU, 2× daily, or (ii) 10 billion CFU, 3× daily, or (iii) placebo Duration: 11 weeks	(i) European Organization for Research and Treatment of Cancer (EORTC-QLQ-C30); (ii) World Health Organization (WHO) toxicity criteria for diarrhea severity; (iii) National Cancer Institute (NCI) scale V3.0 for Abdominal Pain	• Patients operated on and treated with the standard dose of Bifilact had less grade 4 diarrhea (97%) vs placebo group (P = .03). • In Bifilact standard-dose group, 35% of patients were without moderate to severe diarrheal symptoms vs. placebo (17%) after 60 days (P = .04). • For patients who had surgery the standard-dose probiotics reduced incidence of diarrhea of all grades (P = .05). • Probiotic intake did not affect patient QoL. • No significant effects on abdominal pain. • At the end of treatment, Radiation induced diarrhea grades 2-4 was significantly reduced by the standard dose of Bifilact.
Lee et al, 39 Korea	60 survivors of colorectal cancer who completed radiotherapy and chemotherapy within the last 2 years, mean age 56 years, 58.3% male	Randomized, double-blind controlled trial	Treatment: Probiotic “Lacidofil” L. rhamnosus R0011, L. acidophilus R0052, 2 × 109 CFU, 2× daily, or placebo Duration: 12 weeks	(i) ROME III criteria for bowel symptoms (ii) Functional Assessment of Cancer Therapy (FACT-V4) for cancer-related QoL; subscales: FACT-G, FACT-C, FACT-F, FACT-NTX scales (iii) Patient Health Questionnaire (PHQ)-9 for mental health, anxiety and depression domains	• Probiotics significantly decreased the proportion of patients with irritable bowel symptoms (P = .03) • Probiotics significantly improved colorectal cancer-related QoL (FACT-C) (P = .04), cancer-related fatigue (FACT-F) (P = .02), and anxiety and depression (PHQ-9) (P = .01) after 12 weeks • In colorectal cancer survivors, probiotics improved bowel symptoms and quality of life
Linn et al, 40 Myanmar	54 cervical cancer patients completing pelvic radiotherapy and chemotherapy (76%), mean age 55 years, 100% female	Randomized, double-blind controlled trial	Treatment: Probiotic “Biogurt” capsule with 300 g functional yogurt containing 1.75 billion lyophilized live L. acidophilus LA-5 and B. animalis subsp. Lactis BB-12, 3× daily, or placebo Duration: 5 weeks	(i) Common Terminology Criteria for Adverse Events (CTCAE V-4.0) for radiation induced diarrhea and abdominal pain severity	• Significant reduction in radiation induced diarrhea for probiotic group vs. controls (P = .025) • Probiotics significantly attenuated mild-to-moderate (P = .025) and severe (P = .05) diarrhea • Probiotics significantly reduced grade 2 abdominal pain severity and duration of abdominal pain episodes (P’s = .000) • In cervical cancer patients, probiotics significantly reduced the incidence and severity of radiation induced diarrhea and abdominal pain
Liu and Huang, 46 China	100 patients with gastric, colorectal, lymphoma, lung, or other unspecified types of cancer, all receiving chemotherapy, mean age 61 years, 68% male	Single group, pre-post trial	Treatment: Probiotic “Siliankang” Bifidobacterium tetragenous tablets with Bifidobacterium infantis, Lactobacillus acidophilus, Enterococcus faecalis and Bacillus cereus, 3× daily or standard care chemotherapy with no probiotics Duration: 4 weeks	(i) Rome II Chronic functional constipation scale (ii) Wexner constipation scale	• Significant improvement in constipation for 96% of patients in probiotic group, vs 32% in control group (P < .05)
Ohigashi et al, 41 Japan	63 survivors of colon and rectal cancers treated with surgery and pelvic radiotherapy, mean time off treatment 6.5 years, mean age 65 years, 57% male	Single group, pre-post trial	Treatment: Probiotic “The Guard” tablets containing Bacillus natto, Lactobacillus acidophilus, 3 tablets, 3× daily. Total daily dose was 10 mg of B. natto and 30 mg of L. acidophilus Duration: 12 weeks	(i) Medical Outcomes Study Short-Form 36-Item Health Survey (SF-36, V2) for QoL (ii) European Organization for Research and Treatment of Cancer Quality of Life Questionnaire C30 (QLQ-C30, V3) for QoL (iii) Wexner Incontinence scale for functional outcomes	• In the left-side colon cancer group, probiotics significantly improved emotional function (P < .01) • Probiotics significantly improved global QoL for the right-side colon and rectal cancer groups (P’s < .05) • Probiotics significantly improved constipation for the left-side colon and rectal group (P’s < .01) • Probiotics significantly reduced diarrhea in rectal cancer group (P = .01) • In left-side colon group, probiotics significantly attenuated defecation frequency (P < .05) • In right-side colon group, probiotics significantly reduced defecation frequency and frequency of incomplete defecation (P < .05) • For patients who receive rectal resection or right-side colectomy, probiotics may help improve QoL and functional outcomes
Osterlund et al, 47 Finland	150 colorectal cancer patients on chemotherapy (100%), plus radiotherapy (37%), median age 60 years, 51% male	Randomized, controlled trial	Treatment: Synbiotic “Gefilus” Lactobacillus rhamnosus GG 1-2 1010 CFU 2× daily, Gaur gum (prebiotic) 11×g, 1× daily, on chemotherapy cycle days 7-14, for 8 days per month, or no supplement Duration: 24 weeks	(i) Common Toxicity Criteria of the NCI of Canada scale (V2)	• Grade 3-4 diarrhea significantly lower in patients receiving probiotics (P = .027) • Probiotic treatment significantly reduced abdominal pain (P = .025) • 21% of patients receiving probiotics had chemotherapy-dose reductions due to bowel toxicity vs 47% in control patients (P < .00) • No significant effect on overall chemotherapy toxicity, frequency of stomatitis, or neutropenia • No significant effects of gaur gum fiber supplementation • Probiotics significantly improved diarrhea, abdominal pain, and the need for chemotherapy dose reductions
Rosli et al, 42 Malaysia	30 patients with endometrial, cervical, colon, rectal, or prostate cancer receiving pelvic radiotherapy, mean age 57 years, 27% male	Randomized, double-blind controlled trial	Treatment: Prebiotic Partially hydrolyzed guar gum (PHGG; natural water-soluble fiber source) 2× daily, or placebo Duration: 4 weeks	(i) Bristol Stool chart for diarrhea incidence (ii) The European Organization for Research and Treatment of Cancer Care Quality of Life Questionnaire (EORTC-QLQ-C30; V 3.0) for QoL	• Intervention significantly reduced diarrhea frequency by day 45 (P < .05) • No significant difference for QoL scores • Prebiotic PHGG supplementation reduced the frequency of diarrhea following pelvic radiation treatments
Sasidharan et al, 43 India	104 cervical cancer patients receiving pelvic radiation and chemotherapy, mean age 49, 100% female	Randomized, placebo controlled trial	Treatment: Prebiotic 30 g of HAMS Hylon VII resistant starch 2× daily, or placebo Duration: 6 weeks	(i) Common Toxicity Criteria (V3.0), and (ii) Radiation Therapy Oncology Group toxicity scale for diarrhea and proctitis severity	• No significant effects of the intervention on diarrhea or proctitis symptoms • No significant benefit of administering resistant starch to patients receiving pelvic radiotherapy
Shao et al, 44 China	46 patients with abdominal or pelvic cancer completing radiotherapy or within 3 weeks post-radiotherapy, mean age 60 years, 48% male	Randomized, controlled trial	Treatment: Probiotic “Golden Bifid” with Bifidobacterium, lactobacillus and Streptococcus thermophilus, 0.35 g/capsule, Bifidobacterium adolescent 0.5 Billion CFU, 3 tabs 3× daily, and Glutamine enteric capsule (0.25 g/capsule) 2 capsules 2× daily, and Fish oil capsule (1200 mg/capsule), 1 capsule 3× daily, or Peptisorb Duration: 2 weeks	Not specified	• Occurrence rate of abdominal pain, flatulence and diarrhea on 7 and 14 days post-treatment was significantly lower in treatment group vs controls (P < .05) • In patients with acute radiation enteritis, enteral nutrition may improve bowel function
Wierdsma et al, 45 The Netherlands	32 head and neck cancer survivors, mean age 58 years, 75% male	Prospective, randomized, double-blind pilot trial	Treatment: Prebiotic Standard no residue tube feeding with: (i) “Osmolite” non-fructooligosaccharides (FOS) group with no fiber, (ii) FOS and fiber-enriched with “Jevity FOS” 10.6 g fiber, 7 g FOS per liter, or (iii) control (standard western diet) Duration: 6 weeks	(i) Gastrointestinal Quality of Life Index (GIQLI) questionnaire for gastrointestinal QoL	• GIQOL in the FOS group remained stable, but in the non-FOS group decreased significantly during the 6 weeks intervention (P = .027). • Prebiotic tube feeding with FOS may improve patient QoL byway of modulating the gut microbiota, specifically increasing Bifidobacteria.
Yoon et al, 48 Korea	36 rectal cancer patients, stages 1-3, receiving surgery for lower anterior resection and ileostomy reversal, plus preoperative chemoradiation (69.4%) completed 5 months prior. Mean age of 60 years, 64% male	Randomized, double-blind, placebo-controlled pilot trial	Treatment: Probiotic Lactobacillus plantarum CJLP243 (KCCM11045P), isolated from kimchi, 1× daily at a dose of 1 × 1010 or placebo, beginning 1 day after surgery Duration: 3 weeks	(i) Memorial Sloan Kettering Cancer Centre (MSKCC) Bowel Function Index (BFI) and LARS scores (ii) EORTC: QLQ-C30, QLQ-CR29	• No significant effects for GI or QOL outcomes