Effects of a butyrate enema on systemic concentrations of short chain fatty acids

Short chain fatty acids (mainly butyrate, acetate, and propionate) are produced
in the large intestine by bacterial fermentation of undigested carbohydrates,
such as dietary fibres. Butyrate is an important energy source of the
intestinal epithelium and has a pivotal role in the regulation of epithelial
cell proliferation and differentiation, immune function and mucosal protection.
Non-digestible carbohydrates (prebiotics) increase the concentrations of
colonic butyrate, which has been proposed to be responsible for their
beneficial effects. Furthermore, butyrate has been proven to be effective in
the treatment of active ulcerative colitis, diversion colitis, short bowel
syndrome and pouchitis.
In the present study, the interorgan metabolism of short chain fatty acids will
be studied, with special interest in butyrate metabolism. Patients undergoing
upper abdominal surgery were chosen as study population and will receive a
butyrate enema during surgery. After administering this enema, portal,
arterial and hepatic venous SCFA concentrations will be measured in plasma.
This study population has been chosen, because the required blood vessels are
accessible during this type of surgery. The design used to study the effects of
butyrate administration will be an interventional design. Butyrate is generally
not a dietary ingredient itself, but is mainly produced after the ingestion of
dietary fibre, and as it will be given to patients using a rectal enema, this
study is listed as a pharmaceutical trial. The EudraCT number issued for this
study is: 2008-000158-11.

In the present study the effects of the colonic administration of butyrate on
portal, hepatic, mesenteric venous and arterial SCFA concentrations will be
studied in patients undergoing major upper abdominal surgery. The aim is to
clarify the interorgan metabolism of short chain fatty acids in human beings.

Three patient groups, butyrate enema, placebo and controls, will be studied.
We first want to test the effects of the vehiculum (60 ml enema without
butyrate) in 5 patients, because there might be the possibility of dilution of
SCFA already present in the sigmoid and as a result increased absorption might
occur. The butyrate enemas will be used in 10 patients and another 5 patients
will serve as controls, in which no intervention is done.

patients receive either a butyrate enema, placebo or serve as control group.

According the blood sampling: The methods applied (intra-abdominal blood
sampling) have been used without any problems for the surgical procedure or the
patients (MEC 02-045, MEC 03-032, MEC 06-2067) and as published by Van de Poll
et al [17].
According to the enema: Enemas are clinically used for several purposes, for
example to remove faeces when an individual is constipated, to cleanse the
rectum as preparation for an endoscopic examination, or to administer drugs or
analgetic agents. Enemas differ greatly in volume (3 ml - 1 L) depending on the
area of the colon that has to be reached by the fluid. In the present study 60
ml enemas will be used. In a prior study this relatively small volume was
easily tolerated (MEC 04 127). Another study using enemas of 100 ml in patients
with Ulcerative Colitis also reported no irritation or consecutive bowel
movements or other side effects due to the enema