Exploring colonic fermentation and new technical applications for understanding functional & inflammatory bowel disease
Chu Kion Yao
10.4225/03/58f6c6e37ce5f
https://bridges.monash.edu/articles/thesis/Exploring_colonic_fermentation_and_new_technical_applications_for_understanding_functional_inflammatory_bowel_disease/4887374
The colonic
microbiota has major functions in the fermentation and metabolism of undigested
dietary substrates. Abnormalities in these metabolic functions have been
implicated in the pathogenesis of functional bowel disorders (FBD) and
ulcerative colitis (UC). Restoration of these functions could potentially
provide an opportunity for formulating new therapies. However, research is
currently hampered by physical inaccessibility of colonic contents and
inaccurate measurements of highly volatile metabolites such as hydrogen
sulphide (H<sub>2</sub>S). Biomarkers to target and measure success of therapy are also
lacking. <br>
<br>
This thesis aims to investigate the utility of new systems
that profile the modulation of bacterial metabolites in a series of studies.
These included (i) breath hydrogen testing in the management of FBD patients,
(ii) a novel faecal gas-profiling system in the modulation of H<sub>2</sub>S and nitric
oxide for ulcerative colitis, (iii) an ingestible pH-motility capsule in
assessing colonic fermentation and regional pH profiles with regards to
pH-dependent drug delivery systems; and (iv) a novel ingestible gas-sensing
capsule in assessing colonic gas production in response to dietary manipulation
of fermentable fibre. <br>
<br>
Findings from a retrospective evaluation of FBD patients with
repeated lactulose and fructose breath hydrogen tests demonstrated poor
test-retest reproducibility of testing outcomes and a poor ability to predict
gastrointestinal symptoms. Hence, routine use of lactulose and fructose breath
tests to guide clinical management of these patients was not recommended. <br>
<br>
Investigation of the newly developed faecal-gas profiling
system in a proof-of-concept study was successful in producing reliable and
accurate real-time measurements of faecal gas production, specifically H<sub>2</sub>S.
Subsequently, assessment of H<sub>2</sub>S modulation <i>in vitro </i>identified that faecal H<sub>2</sub>S
production was altered in a small cohort of UC patients, effectively suppressed
by readily fermentable carbohydrates, vigorously stimulated by sulphur amino
acids but minimally affected by 5-aminosalicylic acid and inorganic sulphur.
These results have implications for the future design of dietary therapies to
reduce excessive colonic H<sub>2</sub>S production implicated in UC and the utility of the
technology as a biomarker for monitoring treatment success. <br>
<br>
The results of a randomised, double-blind, cross-over
intervention study in patients with clinically quiescent UC documented features
of reduced carbohydrate fermentation in comparison to healthy volunteers using
the ingestible pH-motility capsule. A proportion of patients with UC also had
colonic pH profiles that were sub-optimal for the activation of pH-dependent
drug delivery systems. Acute supplementation of fermentable and slowly
fermentable carbohydrates improved pH profiles in the proximal colon and normalised
colonic transit but did not correct for impaired fermentative activity in the
distal colon. <br>
<br>
In another proof-of-concept trial, divergent patterns of
intestinal carbon dioxide production were detected in real time by the
gas-sensing capsule following dietary interventions with high and low
fermentable fibre content in a pig model. However, further animal trials are
needed to improve its operation and safety before use in human trials. <br>
<br>
In conclusion, accurate and reliable systems are now
available to measure the functional capacity of the colonic microbiota and
create new frontiers in nutrition and gastroenterology research. These systems
enabled identification of pathological and regional differences in the function
of the microbiota in UC compared to health that will have implications in the
design of new dietary therapies and drug delivery systems in UC. Further work
is needed to expand on these preliminary findings.
2017-04-19 02:09:37
Gas
Dietary fibre
Ulcerative colitis
Colonic fermentation
Hydrogen sulphide
Functional bowel disorders
Protein
Diet
Nutrition and Dietetics not elsewhere classified