Human studies demonstrated that dysbiosis at least occurs among patients with cancer, particularly colorectal cancer (CRC).
A small study of 47 CRC cases and 94 controls found that patients with CRC had lower microbial diversity (number of taxa present) than controls, particularly with less Clostridia and more Fusobacterium, and Porphyromonas.3 Risk of CRC was associated with increased amount of Atopobium (odds ratio [OR], 14.36; 95% CI, 2.78-74.30; P < .001), Porphyromonas (OR, 5.17; 95% CI, 1.75-15.25; P = .001), and Fusobacterium (OR, 4.11; 95% CI, 1.62-10.47; P = .004). Another larger study found a difference in microbiota composition among patients with CRC compared with healthy patients, with Bacterioides/Prevotella in significantly greater abundance in patients with CRC (P = .009).4
One study sought to develop a screening tool for CRC by evaluating the microbiome of healthy patients and patients with adenoma and carcinoma.5 Patients with adenoma harbored higher amounts of Ruminococcacea, Clostridium, Pseudomonas, and Porphyromonadacea and lower levels of Bacteroides, Lachnospiraceae, Clostridiales, and Clostridium compared with healthy patients.
Patients with carcinoma harbored higher levels of Fusobacterium, Porphyromonas, Lachnospiraceae, and Enterobacteriaceae, and lower amounts of Bacteroides, Lachnospiraceae, and Clostridiales compared with healthy patients. The additional abundance of 5 or 6 microorganisms to the predictive models of adenoma (age and race) or carcinoma (age, race, and body mass index), respectively, greatly increased sensitivity and specificity of identifying patients with lesions.
Other studies have consistently demonstrated that the levels of Fusobacterium spp. and Porphyromonas are higher and Clostridia and Lachnospiraceae are lower among patients with CRC and within tumors versus adjacent normal tissue.6-8 One study detected Fusobacterium nucleatum in 13% of colon and rectal cancer cases from the Nurses’ Health Study and the Health Professionals Follow-up Study, and demonstrated that the presence of Fusobacterium nucleatum was significantly associated with lower levels of CD3-positive T cells.9
A small, randomized study demonstrated that perioperative probiotics increase microbiota diversity and decrease the abundance of Fusobacterium among patients with CRC compared with others.10 The relative levels of microbiota taxa returned to that similar of healthy volunteers. Another randomized study demonstrated that patients with CRC who received probiotics prior to CRC surgery had improved gut mucosal barrier and decreased infectious complications compared with patients who did not receive probiotics.11
A study of patients with gastric cancer demonstrated that patients had a thicker tongue coating of microbiota, which had lower diversity, than healthy patients.12 Another study demonstrated dysbiosis in the oral microbiota among patients with laryngeal squamous cell carcinoma. The larynx and throat microbiota was substantially different between patients with laryngeal carcinoma and healthy subjects (P = .006), including a greater abundance of Fusobacterium, Prevotella, and Gemella and lower levels of Streptococcus and Rothia compared with healthy subjects.13
Several studies also demonstrated that patients with gastric cancer harbor a less-diverse gut microbiota than do healthy patients, particularly among patients who were positive for Helicobacter pylori.14
Stem Cell Transplantation
The effects of the microbiota on the outcomes of allogeneic stem cell transplantation (allo-SCT) are mixed. One study demonstrated no significant difference in survival, non-relapse mortality, and incidence of graft-vs-host-disease between patients with low or moderate to high microbial diversity when the microbiota was sampled about 2 weeks prior to conditioning.15
Another study, however, demonstrated significantly worse mortality outcomes among patients with lower intestinal microbiota diversity, with a 3-year overall survival of 36% compared with 60% and 67% among patients with intermediate or high diversity (P = .019). This association remained after multivariate adjustment for other clinical predictors of transplant-related mortality (hazard ratio, 5.25; P = .014). In this study, the microbiota was sampled at the time of stem cell engraftment.16
Evidence suggests that microbiota dysbiosis occurs among patients with cancer, particularly those with cancers of the digestive tract. The mechanisms by which this occurs and the timing of the dysbiosis are not clear. More and larger studies are needed to determine whether microbiota screening can identify patients at risk of developing cancer and whether modulation of the microbiota with probiotics or by other means can prevent or treat cancer, or augment other treatment modalities.
- Dzutsev A, Goldszmid RS, Viaud S, Zitvogel L, Trinchieri G. The role of the microbiota in inflammation, carcinogenesis, and cancer therapy. Eur J Immunol. 2015;45:17-31. doi: 10.1002/eji.201444972
- Garrett WS. Cancer and the microbiota. Science. 2015;348:80-6. doi: 10.1126/science.aaa4972
- Ahn J, Sinha R, Pei Z, et al. Human gut microbiome and risk for colorectal cancer. J Natl Cancer Inst. 2013;105;1907-11. doi: 10.1093/jnci/djt300
- Sobhani I, Tap J, Roudot-Thoraval F, et al. Microbial dysbiosis in colorectal cancer (CRC) patients. PLoS One. 2011;6:e16393. doi: 10.1371/journal.pone.0016393
- Zackular JP, Rogers MA, Ruffin RT 4th, Schloss PD. The human gut microbiome as a screening tool for colorectal cancer. Cancer Prev Res (Phila). 2014;7:1112-21. doi: 10.1158/1940-6207.CAPR-14-0129
- Kostic AD, Chun E, Robertson L, et al. Fusobacterium nucleatum potentiates intestinal tumorigenesis and modulates the tumor immune microenvironment. Cell Host Microbe. 2013;14:207-15. doi: 10.1016/j.chom.2013.07.007
- Sinha R, Ahn J, Sampson JN, et al. Fecal microbiota, fecal metabolome, and colorectal cancer interrelations. PLoS One. 2016;11:e0152126. doi: 10.1371/journal.pone.0152126
- Mira-Pascual L, Cabrera-Rubio R, Ocon S, et al. Microbial mucosal colonic shifts associated with the development of colorectal cancer reveal the presence of different bacterial and archaeal biomarkers. J Gastroenterol. 2015;50:167-79. doi: 10.1007/s00535-014-0963-x
- Mima K, Sukawa Y, Nishihara R, et al. Fusobacterium nucleatum and T cells in colorectal carcinoma. JAMA Oncol. 2015;1:653-61. doi:10.1001/jamaoncol.2015.1377
- Gao Z, Guo B, Gao R, Zhu Q, Wu W, Qin H. Probiotics modify human intestinal mucosa-associated microbiota in patients with colorectal cancer. Mol Med Rep. 2015;12:6119-27. doi: 10.3892/mmr.2015.4124
- Liu Z, Qin H, Yang Z, et al. Randomised clinical trial: the effects of perioperative probiotic treatment on barrier function and post-operative infectious complications in colorectal cancer surgery – a double-blind study. Aliment Pharmacol Ther. 2011;33:50-63. doi: 10.1111/j.1365-2036.2010.04492.x
- Hu J, Han S, Chen Y, Ji Z. Variations of tongue coating microbiota in patients with gastric cancer. BioMed Res Int. 2015;173729. doi: 10.1155/2015/173729
- Gong HL, Shi Y, Zhou L, et al. The composition of microbiome in larynx and the throat biodiversity between laryngeal squamous cell carcinoma patients and control population. PLoS ONE. 2013;8:e66476. doi: 10.1371/journal.pone.0066476
- Dias-Jácome E, Libânio D, Borges-Canha M, Galaghar A, Pimentel-Nunes P. Gastric microbiota and carcinogenesis: the role of non-Helicobacter pylori bacteria – a systematic review. Rev Esp Enferm Dig. 2016;108:530-40. doi: 10.17235/reed.2016.4261/2016
- Doki N, Suyama M, Sasajima S, et al. Clinical impact of pre-transplant gut microbial diversity on outcomes of allogeneic hematopoietic stem cell transplantation. Ann Hematol. 2017;96:1517-23. doi: 10.1007/s00277-017-3069-8
- Taur Y, Jeng RR, Perales MA, et al. The effects of intestinal tract bacterial diversity on mortality following allogeneic hematopoietic stem cell transplantation. Blood. 2014;124:1174-82. doi: 10.1182/blood-2014-02-554725