The perioperative microbiota composition in colorectal surgery patients receiving oral antibiotics or no oral antibiotics

Surgery remains the cornerstone in the curative treatment for colorectal
cancer. Despite the introduction of improvements in perioperative care,
infectious complications after surgery remain a burden for patients and
health-care expenses. Several recent randomized controlled trials show that
oral antibiotic prophylaxis is associated with a reduction of postoperative
infectious complications and potentially anastomotic leaks [1-4]. The
SELECT-trial showed that patients who received oral antibiotic prophylaxis in
the form of SDD had a significant reduction of preoperative Proteobacteria
levels in their gut microbiota [1]. Subsequently, we also presented data which
show that decreased levels of Proteobacteria were associated with a reduction
in infectious complications [5]. Although this explicit evidence for a decrease
in post-operative infectious complications, data on correlation between oral
antibiotic prophylaxis like SDD and its effect on microbiota in the
perioperative phase is scarce. Therefore, several important questions remain to
be answered. First, it is currently unknown how the patient*s microbiota
composition changes and repopulates in the perioperative phase and whether this
can be predicted based on the original microbiota in patients using oral
antibiotic prophylaxis as well as in control patients that not received oral
antibiotics. Secondly, it is uncertain if swabs of the rectal microbiota are
representative for the microbiota located at the site of the anastomosis (i.e.
right sided colon or sigmoid). Thirdly, it is still unclear whether specific
bacterial species can be identified as the cause of infectious complications,
as suggested in our previous study [6]. The latter two questions are important
as it has been proposed in animal studies that the presence of certain bacteria
at the anastomotic site may cause or increase the risk of anastomotic leakage
[7]. Fourthly, it is unknown what effect antifungal medication such as
amphotericin B in SDD has on the perioperative microbiota composition.
In addition, this study will provide knowledge on the prognostic value of a
rectal swab for possible anastomotic complications.

Primary Objective: Exploring peri-operative changes in microbiota composition
between patient receiving oral antibiotics, oral antibiotics with amphotericin
B or no oral prophylaxis, performed by 16S rRNA sequencing, analyzed by
Microbiome Center Amsterdam (MiCA).
Secondary Objective(s):
1. Comparison of peri-operative changes in microbiota composition between colon
cancer patients receiving preoperative oral antibiotic prophylaxis with or
without amphotericin B.
2. Correlation between the gut microbiota composition and specific microbiota
on site of an occurring post-operative infection.
3. Comparison of rectal and anastomotic microbiota composition for right and
left sided colon resections

Prospective multicenter observational cohort study including a total of 120
patients, for each patient 5 swabs are taken on 4 time points, see figures 1
and 2. Follow-up is done in accordance with the Dutch guidelines on colorectal
cancer. Duration of the study is 12 months, excluding follow-up.

Patients will undergo multiple peri-operative rectal swabs as well as an
intra-operative swab from proximal and distal anastomotic and tumour sites. No
negative side effects are anticipated besides minor discomfort of a rectal swab
on the outpatient clinic.