Comparison of Microbiota in Patients Treated by Surgery or Chemotherapy by 16S rRNA Sequencing Reveals Potential Biomarkers for Colorectal Cancer Therapy

Abstract

Colorectal cancer (CRC) is the third most diagnosed cancer worldwide due to its high difficulty in early diagnosis, high mortality rate and short life span. Recent publications have demonstrated the involvement of the commensal gut microbiota in the initiation, progression and chemoresistance of CRC. However, this microbial community has not been explored within CRC patients after anti-cancer treatments. To this end, we performed next generation sequencing-based metagenomic analysis to determine the composition of the microbiota in CRC patients after anti-cancer treatments. The microbial 16S rRNA genes were analyzed from a total of 69 fecal samples from four clinical groups, including healthy individuals, CRC patients, and CRC patients treated with surgery or chemotherapy. The findings suggested that surgery greatly reduced the bacterial diversity of the microbiota in CRC patients. Moreover, Fusobacterium nucleatum were shown to confer chemoresistance during CRC therapy, and certain bacterial strains or genera, such as the genus Sutterella and species Veillonella dispar, were specifically associated with CRC patients who were treated with chemotherapeutic cocktails, suggesting their potential relationships with chemoresistance. These candidate bacterial genera or strains may have the ability to enhance the dosage response to conventional chemotherapeutic cocktails or reduce the side effects of these cocktails. A combination of common CRC risk factors, such as age, gender and BMI, identified in this study improved our understanding of the microbial community and its compositional variation during anti-cancer treatments. However, the underlying mechanisms of these microbial candidates remain to be investigated in animal models. Taken together, the findings of this study indicate that fecal microbiome-based approaches may provide additional methods for monitoring and optimizing anti-cancer treatments.

Moderate alteration to gut microbiota brought by colorectal adenoma resection

“…Recent research has found great alterations of gut microbiota after the removal of colorectal carcinoma in favor of a more normal microbiota . Moreover, reduced microbial diversity has been reported among CRC patients treated with surgery, while few alterations occur because of the adenoma resection, which is similar to our finding. The reason might be that the impact of carcinoma on the intestinal environment is much greater than adenoma, thus reflecting their corresponding impact on the microbiota.…”

The Role of Gut Microbiome Perturbation in Fatigue Induced by Repeated Stress from Chemoradiotherapy: A Proof of Concept Study

“…Similarly, a small study (n � 11) among mixed pelvic cancer patients, using 454 high-throughput pyrosequencing, found a significant decrease in the Shannon diversity index after pelvic RT compared with before RT [14]. Interestingly, one cross-sectional study compared the fecal microbiota of 33 healthy individuals, 17 colorectal cancer (CRC) patients before treatment, 14 CRC patients treated with chemotherapy, and 5 CRC patients after surgery, but found no significant differences in alpha diversity indexes among groups [29]. Nonetheless, our study findings suggest that the global balance of bacterial populations in the gut changed in response to genotoxic stress such as CRT.…”

Pancreatic Cancer, Gut Microbiota, and Therapeutic Efficacy

“…Zhang et al [26] 5-Fluorouracil Fusobacterium nucleatum Nonbeneficial Induce BIRC3 expression via theTLR4/NF-κB pathway Yuan et al [27] 5-Fluorouracil Antibiotics increase Proteobacteria Nonbeneficial -Deng et al [28] Tegafur plus oxaliplatin Fusobacterium nucleatum Nonbeneficial -Geller et al [29] Gemcitabine Gammaproteobacteria Nonbeneficial Bacterial CDD inactivates gemcitabine Yu et al [30] 5 Attention has been paid to ICIs in the clinic. Immunotherapy targeting PD-1 has emerged as an effective strategy for the treatment of several cancers.…”

“…Distinct responses to chemotherapy and immunotherapy in cancer patients have provoked robust interest in identifying useful biomarkers to optimize patient selection and management. Fecal sample analysis using 16S rRNA sequencing has provided evidence that Fusobacterium nucleatum is related to the chemoresistance of CRC, as well as other specifically chemotherapy-associated bacterial strains [28]. This may be an optimal microbial marker candidate during anticancer treatment.…”