Introduction
5-Fluorouracil (5-FU) remains the cornerstone of palliative and adjuvant chemotherapy of colorectal cancer (CRC) [1, 2]. The majority of patients with advanced CRC are initially responsive to the implementation of 5-FU-based combination regimens and 5-FU pro-drugs [3, 4]. However, the 5-year survival rate eventually demonstrates lower than 10% in these CRC patients [5]. Unfortunately, colorectal tumors are generally not responsive to novel immune checkpoint therapy [6]. Thus, it is of paramount significance to elucidate the underlying risk factors of 5-FU resistance, which aims to reform the guidelines of 5-FU diagnostics and treatments for CRC patients.
CRC chemoresistance results from the complex crosstalk between gene regulation and the environment. Accumulating evidence indicates that gut microbiota is linked to the initiation and development of CRC via affecting intestinal inflammation and DNA mutations [7-10]. However, few studies have focused on their host response to CRC treatment. This systematic review has summarized the clinical correlations between 5-FU resistance of CRC and three common intestinal bacteria, includingFusobacterium nucleatum , Bacteroides fragilis andEscherichia coli .
Fusobacterium nucleatum (F. nucleatum , Fn ), a human’s oral cavity colonizer, has been frequently reported to enrich in stools from CRC patients as compared with the normal controls [11-13]. The previous study has revealed that F. nucleatumoverabundance could impair the therapeutic efficacy of 5-FU by inducing LC3-II expression, autophagic flux and autophagosome synthesis in colorectal cancer [14]. Besides, the amount of F. nucleatumis associated with the upregulation of BIRC3 in CRC cells cocultured with Fn , which revealed Fn inhabiting in intestinal lumen of CRC patients can directly impair the efficacy of 5-FU [15].Bacteroides fragilis (B. fragilis ), is the most frequent anaerobe isolated from clinical cases of diarrhea, peritonitis, intra-abdominal abscesses and sepsis [16-19]. Several studies showed the significant correlation between the presence of B. fragilisin stool or colonic biopsy specimens and poor prognosis of CRC [20-22]. The detection of B. fragilis may be a potential marker for the diagnosis of colorectal cancer. Despite the fact thatEscherichia coli (E. coli ) is a commensal bacterium of the human microbiota and represents the most common cultivable, gram-negative, aero-anaerobic bacteria [23, 24], various studies have demonstrated a clear link between mucosa-adherent E. coliand colorectal cancer [20, 25].
Although mechanisms and causalities between the above three intestinal bacteria and 5-FU resistance of CRC have been still uncovered, some studies have explored the diagnostic performance of their presence in feces or tumor tissues in 5-FU-treated CRC patients. This meta‑analysis has summarized the published data which aims to evaluate the value ofF. nucleatum , B. fragilis or E. coli detection in 5-FU efficacy for CRC treatment.