Functional gastrointestinal disorders (FGID) are common in the general population.
Symptoms such as pain, nausea, bloating, diarrhea or constipation may occur. Irritable
bowel syndrome (IBS) is the most common FGID with a prevalence in the range of 5-25%.
Medical attention is sought by 20-75% of patients who meet diagnostic criteria for IBS at
some time in their lives. Quality of life is often impaired in IBS patients. In previous
studies a diet low in FODMAP was shown to reduce gastrointestinal symptoms in IBS
patients.
But still it is unknown which FGID patients (e.g. patients with irritable bowel syndrome,
functional dyspepsia (FD), functional abdominal pain/bloating) profit most from such a
diet which involves costs, time and significant lifestyle alteration.
To test for food intolerances, standard hydrogen breath tests using fructose or lactose
as challenge substance are still commonly used and do present a nutritional challenge,
however the usefulness of information gained is questionable. Fructose intolerance is as
prevalent in IBS as in healthy volunteers, in fact when tested with the usual doses of
25-50g, prevalence of fructose intolerance ranges between 53% and 73%. Testing (genetic)
for hypolactasia, is often, even in the professional setting, misunderstood as lactose
intolerance testing. Most patients, who do have hypolactasia, i.e. almost no activity of
intestinal brush-border enzyme lactase, tolerate up to 12g of lactose per day, remain
asymptomatic and therefore should not be considered lactose intolerant. In addition, one
must realize, that the vast majority in the world is hypolactasic and hypolactasia, or
rather lactase persistence, constitutes a norm variant.
Recently it was shown that a standardized liquid mixed nutrient meal including 25g
lactulose, but not with 15g lactulose, allows differentiation of IBS patients from
healthy controls. This test, incorporating FODMAP lactulose, that, unlike lactose and
fructose, is indigestible in all humans in the small intestine, plus a caloric load,
reflecting a regular meal and everyday life, has therefore the potential to be a useful
marker of nutrient intolerance in patients with suspected functional bowel disease.
Additionally, associations between FGID and JH/JHS have been recognized in the past
decade. JH/JHS constitutes a hereditary disorder of connective tissue in which patients
often report non-musculoskeletal symptoms, among them gastrointestinal complaints.
Previous studies in Europe and the U.S. have reported a JHS prevalence of 20% in the
general population.
A stringent approach to studying possibly JH and JHS-related changes with diagnostic and
interventional arms, such as a nutrient challenge testing or dietary adaptation
(i.e.FODMAP diet, 2-food-elimination diet) has not yet been taken.
Differences in the intestinal microbiome have been shown in IBS patients compared to
healthy volunteers but not in JHS compared to non-JHS patients. Given the differences
noted in patients' symptomatology, the preliminary data on gut function and the
underlying structural abnormalities, the role of microbiome in relation to FGID and JHS
is highly interesting and, as yet, unstudied. In recent years with the advent of more
powerful sequencing tools, a number of studies have been published, that try to
characterize the microbiome in IBS patients. Research on IBS-related changes of the
microbiome is early and incomplete. The number of literature reviews regarding gut
microbiome currently far exceeds the number of original articles reporting on the
microbiome in functional bowel disease. IBS-specific interventional studies are even
rarer and when performed, often lack control groups and the reality of multiple or
repeated intervention, that characterize treatment of FGID. Therefore, and to identify
patients according to their microbiome which profit most from therapeutic intervention
(such as FODMAP diet, 2-food elimination diet) we are also going to analyze microbiome
changes before and after dietary intervention.
Another pathological, impairing aspect of IBS patients is the intestinal
hypersensitivity. Anorectal hypersensitivity measurement has been considered a hallmark
for IBS for many years. We are routinely performing anorectal functions tests in our
specialized unit. Recently we validated high-resolution anorectal manometry and rapid
barostat bag measurements to assess visceral sensitivity; in a further study we assessed
obstructive defecation when compared to magnetic resonance defecography. In an earlier
study employing magnetic resonance defecography (MR defecography) we were able to show
that MR defecography, apart from correlating well with the diagnosis of dyssynergic
defecation suggested by anorectal manometry, additional pelvic floor abnormalities such
as pelvic floor descent, cystocele and enterocele could be identified. Studying these
measures in patients with suspected outlet obstruction in relation to JHS status, which
is considered a risk factor for pelvic floor abnormalities, might lead to more focused
diagnostic and therapeutic approaches in the future for patients who profit most from
certain procedures.
Considering all above mentioned facts we are going to carry out a study analyzing
different subtypes of FGID (in particular IBS, FD, functional abdominal pain/bloating)
for demographics, clinical diagnostics (e.g. nutrient challenge testing, microbiome
testing, anorectal manometry and MR defecography), treatment (FODMAP diet) and
comorbidities (in particular JH, JHS and psychological comorbidities) to identify FGID
patients which profit most from different diagnostics and dietary interventions.
