Abstract
Irritable bowel syndrome (IBS) is a common gastrointestinal condition which affects ~11% of the population worldwide. It is heterogeneous in presentation and underlying pathophysiology which has led to difficulties finding optimal treatment for patients. A diet low in fermentable oligosaccharides, disaccharides, monosaccharides and polyols (FODMAP) is effective in reducing symptom severity in ~70% of patients with IBS. This diet reduces fructo-oligosaccharides (FOS) and galacto-oligosaccharides (GOS) intake, and it appears it does not reduce microbial diversity but reduces relative abundance of total Bifidobacterium. Breath testing has been advocated as a diagnostic tool for small intestine bacteria overgrowth (SIBO), however, its clinical utility is debated. The aims of this thesis are to contribute to further understanding of how a low FODMAP diet affects the microbiota: and secondly, to further examine the use of breath tests in gastrointestinal conditions especially IBS.
In the first study, 114 participants with IBS and 62 participants without IBS were enrolled. All participants completed the diet history questionnaire version 2 (DHQ II), the hospital anxiety and depression scale, the physical activity adult questionnaire and provided a faecal specimen for microbiota analysis. Participants with IBS also completed the IBS symptom severity scoring system, the IBS quality of life questionnaire and were tested for SIBO using a glucose breath test. DNA was extracted using the DNAeasy kit with the V4 region of the 16S rRNA gene amplified. DNA was sequenced on Illumina MiSeq. Sequence variants were annotated using the Silva database version 128. Data was treated compositionally. There was no difference in the total gut microbiota or any sequence variants between participants with and without IBS. Similarly, there was no difference in the microbiota by the severity of IBS or any other measured clinical characteristic, including a diagnosis of SIBO. There was a high proportion of participants who appeared to under-report their dietary intake on the DHQ II, with the severity of disease and number of foods the participants reported provoking symptoms being associated with being an under-reporter.
Two participants, one with and one without IBS completed a longitudinal study of two cases where dietary oligosaccharide intake was altered, and the day-to-day effect on the microbiota was measured. In the participant with IBS, the total gut microbiota clustered by diet and in the participant without IBS there was an increase in three sequence variants from Faecalibacterium and one from Roseburia when oligosaccharide intake was increased.
Five participants with IBS completed a pilot study using a wireless motility capsule to measure pH and gastrointestinal transit time when altering FODMAP intake. There was a non-significant increase in whole gastrointestinal transit time when participants changed from their usual diet to a low FODMAP diet from 18:47 hours (11:47-25:17) to 22:08 hours (19:54-78:56) (p=0.125) and through the colon 11:14 hours (4:42-19:14) to 13:54 hours (10:12-68:19) (p=0.1875).
Finally, an audit of 107 patients who had lactulose breath tests with hydrogen and methane analysis was conducted. SIBO was diagnosed as a rise from baseline of ≥20 ppm in either hydrogen or methane, and a methane producer had a baseline reading of ≥5ppm of methane. 10/26 of methane producers had at least one reading lower than their baseline level and 6/26 did not have a significant rise in methane during testing.