Chemistry Reference
In-Depth Information
passage through the stomach of mice, and subsequently altered the interaction of the
prebiotic with the intestinal epithelium.
Lactulose is another prebiotic that has recently demonstrated a capacity to reduce
the severity of DSS colitis in rats.
75
Twice daily prebiotic administration for 6 days
was shown to significantly reduce colonic lesions and MPO activity; however, the
effects on the microbiota were not determined. Furthermore, inulin administration
has also proved efficacious in the setting of DSS colitis, reducing mucosal inflam-
mation, MPO activity, and release of inflammatory mediators, such a prostaglandin
E2.
76
Interestingly, this effect was observed only following oral administration, as
rectal administration of the prebiotic showed no beneficial effects. This is surprising
as the method of administration should not have affected prebiotic availability and
hence its ability to exert it beneficial effects.
As is the case with probiotics, not all prebiotics have demonstrated antiinflam-
matory effects in the setting of IBD, with some prebiotics actually increasing the
severity of damage. FOS is one prebiotic that has demonstrated antagonistic effects
in the intestine. FOS, administered as a dietary supplement (6 percent w/w of total
diet), has been shown to stimulate lactobacilli and bifidobacteria77,78
77,78
and increase
SCFAs in the large bowel (a result that has been replicated in humans with ulcerative
colitis
85
).
86
Therefore, FOS has been proposed to have the capacity to be beneficial
in the IBD setting; however, it has also been demonstrated that, while FOS could
decrease the colonization of pathogenic bacteria, it actually increased translocation
of bacteria, increased mucosal irritation, and increased cecal and colonic MPO activ-
it y.
78
The proposed mechanism of injury involves elevated FOS levels in the cecum
promoting rapid bacterial fermentation, thus increasing organic acid concentrations.
These organic acids then damage the mucosa of the cecum and colon.
87
Interestingly,
however, when FOS was administered by oral gavage in the TNBS rat model of coli-
tis, it was shown to decrease the severity of damage, indicated by increased lactic
acid bacteria, lactate, and butyrate and decreased inflammation scores and MPO
act ivit y.
79
The effect of the route of administration on the efficacy of the prebiotic is
similar to those reported by Moreau et al.
84
and Winkler et al.
83
described above, with
oral administration leading to an increased efficacy of treatment. These inconsistent
findings may be due to differences in the model of colitis, differences between the
remainder of the diet between trials (i.e., levels of fiber, indigestible carbohydrates),
or a result of alterations in the delivery or dosage of FOS, leading to different rates
of fermentation, and in turn SCFA production. Optimizing SCFA production by the
microbiota is an important determinant of probiotic efficacy, as SCFAs are a vital
energy source for intestinal epithelial cells.
12.3.1.2 Prebiotics in Human Trials
Lactulose was recently shown to have no beneficial effects in human IBD patients,
despite promising findings from murine models.
88
Patients were treated with either
10 g of lactulose combined with standard medication or standard medication alone
for 4 months. The study group comprised both UC and CD sufferers, but the results
