Probiotics are live microorganisms that are believed to confer a health benefit to the host when taken in sufficient quantitites.1 The theory underlying their use is that gut dysbiosis — an imbalance in the normal flora of the gastrointestinal (GI) system — may contribute to disease, impaired metabolism, and/or dysregulation of the immune system.2 The gut microbiota consists of all of the commensal microorganisms, including predominately bacteria, but also fungi, archaea, and viruses, and evidence indicates that it participates in a complex interaction with the GI tract and immune system.
The microbiota in the setting of cancer has been an active area of research, particularly for colorectal cancer (CRC).2 According to animal studies, and depending on the predominant strains of the microbiota, microbial-derived factors can promote or suppress tumorigenesis and may modulate the efficacy of anticancer treatments. In addition, administration of probiotics has been shown to modify the microbiota of patients with cancer.3 It has therefore been hypothesized that modulation of the microbiota with probiotics may have positive effects on cancer prevention and treatment.
Supportive Care
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Although there is much excitement about the possibility that probiotics could prevent cancer, the most well-studied use of probiotics is as supportive care for patients undergoing anticancer treatment. Randomized controlled trials (RCTs) suggest that probiotics can reduce certain toxicities associated with chemotherapy and radiation therapy (RT), though the sample sizes of these trials were small.4
Treatment-Induced Diarrhea
A meta-analysis published in 2019 of all RCTs published up to mid-2018 that included 9 trials with a total of 1508 subjects found that probiotics significantly decreased the incidence of RT-induced diarrhea compared with placebo (relative risk [RR], 0.61; 95% CI, 0.45-0.81; P =.0007).5 This effect was particularly evident with more severe diarrhea, including grade 2 or higher (RR, 0.52; 95% CI, 0.30-0.98; P =.02) or grade 3 and higher (RR, 0.32; 95% CI, 0.12-0.82; P =.02). However, a Cochrane meta-analysis found no difference between probiotics and placebo for grade 2 or higher RT-induced diarrhea (risk ratio, 0.75; 95% CI, 0.55-1.03).6 The authors stated that they were unable to conduct a meta-analysis on other outcomes due to heterogeneity.
Most studies suggest that probiotics are effective against chemotherapy-induced diarrhea. The same Cochrane review included 3 RCTs in its analysis and demonstrated that probiotics significantly decreased the occurrence of any diarrhea compared with placebo (pooled risk ratio; 0.59; 95% CI, 0.36-0.96).6
Since this meta-analysis, a phase 1/2 RCT evaluated the effect of high-dose probiotics versus placebo on chemotherapy-induced diarrhea.7 Patients began treatment 2 weeks prior to chemotherapy initiation and continued until 2 weeks after their third cycle. Probiotics significantly decreased the incidence of all grades of diarrhea with 199 cases compared with 220 cases with placebo (P =.019). Though there was a trend toward a lower incidence of grade 3 (8% vs 4%; P =.088) or grade 4 (2% vs 0%; P =.05) diarrhea, the difference was not significant.
Another small RCT assigned patients with lung cancer to receive probiotics or placebo 3 times daily for 3 weeks beginning the day before their first platinum-based multiagent chemotherapy.8 Probiotics were significantly associated with a higher rate of no diarrhea (75%) compared with placebo (38%; P =.017), with lower rates of grade 1 (20% vs 43%) and grade 2 (5% vs 14%) diarrhea, with similar rates of grade 3 (0% vs <1%) diarrhea. There were no reports of grade 4/5 diarrhea. However, there was no difference in the rates of nausea or vomiting between arms.
