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.