Infections

A meta-analysis evaluated clinical trial reports to determine the preventive effect of probiotics on infections associated with CRC resection.9 Probiotics significantly reduced the overall rate of infection post-CRC surgery compared with placebo (odds ratio [OR], 0.51; 95% CI, 0.38-0.68; P =.00), including incision infection (OR, 0.59; 95% CI, 0.39-0.88; P =.01) and the time to flatus (standardized mean difference, -0.70; 95% CI, -1.13 to 0.27; P =.002). There was also a significantly lower rate of pneumonia in the probiotic arm versus the placebo arm (OR, 0.56; 95% CI, 0.32-0.98; P =.04). There were no differences between arms for urinary tract infection, anastomotic leakage, and duration of pyrexia.

Mucositis

A trial evaluated mucositis among randomly assigned patients with advanced nasopharyngeal cancer undergoing chemoradiotherapy 2:1 to receive a probiotic or placebo.10  The treatment included 3 capsules taken twice daily for up to 7 weeks, starting at the beginning of chemoradiotherapy. Probiotics significantly reduced the rate of grade 3 mucositis compared with placebo (16% vs 46%). Probiotics also increased the levels of CD4-, CD8-, and CD3-positive T cells. There was no difference in suppression of bone marrow, levels of lymphocytes, leukocytes, hemoglobin, or albumin, or weight loss.

Adjunctive Treatment

Animal studies suggest that the composition of the microbiota is important for efficacy of anticancer therapies.2 For example, tumor-bearing mice whose microbiota is depleted fail to respond to chemotherapy, and combined treatment with chemotherapy and probiotics improves efficacy. Similarly, enrichment of mouse microbiota with certain bacterial strains enhances the efficacy of immune checkpoint inhibitors. In humans, one study found an association between the administration of antibiotics with immune checkpoint inhibitors with antibiotics and lower survival rate. In addition, several studies suggest that the microbiota of patients who respond to immune checkpoint inhibition differs from those patients who do not respond. Therefore, the theory of treating patients with antibiotics during anticancer therapy is currently a topic of ongoing research.

Safety of Probiotics

Probiotics are widely marketed as a safe means to improve health among healthy individuals and to modify disease processes.11 Although it appears that probiotics are associated with few adverse events (AEs), it is important to note that there is no structured reporting of AEs for manufacturers and studies may or may not report AEs. Therefore, the true incidence of AEs is unknown. In addition, there is no regulation regarding what manufactures claim are in their product, in terms of live organisms and the type of organisms, as probiotics generally fall into the realm of supplements, which have limited regulatory oversight by the US Food and Drug Administration (FDA). Cross-contamination with strains has been observed, and among manufacturing facilities determined by FDA to have violated regulations related to current good manufacturing practices, the identity, purity, strength, and composition of the probiotic product were called into question.

In the literature, few AEs have been reported. A meta-analysis of 6 RCTs among healthy adults found no significant difference from placebo in the rate of AEs, including gastrointestinal, respiratory, thoracic, and mediastinal disorders; as well as infections.12

In a meta-analysis that included 5 RCTs that reported AEs, there were 5 studies in which patients reported adverse reactions among 2242 study participants (approximately 0.2% of studies).4 Another study retrospectively identified a rate of 0.5% (19 of 3796 patients) for bloodstream infections among immunocompromised patients with cancer who had undergone hematopoietic cell transplant within the prior year.13

Conclusions

Several small RCTs suggest that probiotics may help reduce the incidence and/or severity of anticancer treatment-induced toxicities, particularly diarrhea, postsurgical infections, and mucositis. Probiotics appear to be associated with few AEs, though it is important to note that the United States does not regulate the labeling of probiotics. Bloodstream infections are possible, although rare, particularly among patients who are immunocompromised.

References

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  2. Vivarelli S, Salemi R, Candido S, et al. Gut microbiota and cancer: from pathogenesis to therapy. Cancers (Basel). 2019;11(1):38.
  3. Gao Z, Guo B, Gao R, Zhu Q, Qu W, Qin H. Probiotics modify human intestinal mucosa-associated microbiota in patients with colorectal cancer. Mol Med Rep. 2015;12(4):6119-6127.
  4. Hassan H, Rompola M, Glaser AW, Kinsey SE, Philips RS. Systematic review and meta-analysis investigating the efficacy and safety of probiotics in people with cancer. Support Care Cancer. 2018;26(8):2503-2509.
  5. Qiu G, Yu Y, Wang Y, Wang X. The significance of probiotics in preventing radiotherapy-induced diarrhea in patients with cervical cancer: A systematic review and meta-analysis. Int J Surg. 2019;65:61-69.
  6. Wei D, Heus P, van de Wetering FT, van Tienhoven G, Verleye L, Scholten RJ. Probiotics for the prevention or treatment of chemotherapy‐ or radiotherapy‐related diarrhoea in people with cancer. Cochrane Database Syst Rev. 2018;8:CD008831.
  7. Sharma A, Chaudhary SP, Raina V, et al. Final results of a phase II/III, randomized, double blind, placebo-controlled study to investigate the efficacy of a high potency multistrain probiotic, on chemotherapy induced diarrhea in cancer patients receiving Fluropyrimidines and/or Irinotecan based therapy. Ann Oncol. 2018;29(suppl 8;abstr 16820_PR):mdy424.085.
  8. Tian Y, Li M, Song W, Jiang R, Li YQ. Effects of probiotics on chemotherapy in patients with lung cancer. Oncol Lett. 2019;17(3):2836-2848.
  9. Ouyang X, Li Q, Shi M, et al. Probiotics for preventing postoperative infection in colorectal cancer patients: a systematic review and meta-analysis. Int J Colorectal Dis. 2019;34:459-469.
  10. Jiang C, Wang H, Xia C, et al. A randomized, double-blind, placebo-controlled trial of probiotics to reduce the severity of oral mucositis induced by chemoradiotherapy for patients with nasopharyngeal carcinoma. Cancer. 2019;125(7):1081-1090.
  11. Cohen PA. Probiotic safety—no guarantees. JAMA Intern Med. 2018;178(12):1577-1578.
  12. Tapiovaara L, Lehtoranta L, Poussa T, Mäkivuokko H, Korpela R, Pitkäranta A. Absence of adverse events in healthy individuals using probiotics—analysis of six randomized studies by one study group. Benef Microbes. 2016;7(2):161-169.
  13. Cohen SA, Woodfield MC Boyle N, Stednick Z, Boeckh M, Pergam SA. Incidence and outcomes of bloodstream infections among hematopoietic cell transplant recipients from species commonly reported to be in over-the-counter probiotic formulations. Transpl Infect Dis. 2016;18(5):699-705.