Background:
Chronic inflammatory bowel disease (IBD) affects the lives of millions of people
worldwide due to recurrent, severe clinical symptoms, potential complications and ongoing
medical interventions. The scientific community currently assumes a multicausal
pathogenesis in IBD caused by an unfavorable constellation of genetic predisposition,
imbalance of pathogenic to symbiotic gut bacteria (dysbiosis) and harmful environmental
and lifestyle factors resulting in an excessive immune response.
The intestinal barrier and the microbiome play a key role in maintaining intestinal
balance and health. The intestinal barrier protects our body from bacteria, viruses and
fungi in the intestinal lumen, while it enables the absorption of nutrients at the same
time. In case of a leaky gut, microbial pathogens or their components can enter the
deeper cell layers of the intestine and cause acute and long-term inflammatory reactions.
The composition of the gut microbiome, i.e. the community of billions of microorganisms
living in the gut, has a significant influence on the intestinal barrier and gut health.
Beneficial bacteria stabilize the intestinal barrier, strengthen local defenses (mucin
and IgA production) and inhibit pro-inflammatory immune reactions and cell death. In
contrast, harmful bacteria (pathobionts) disrupt the intestinal barrier, dysregulate cell
death and proliferation, which leads to the release of pro-inflammatory signaling
substancesand and an immune response causing inflammation.
While previous attempts to develop pharmacological therapies to improve gut barrier
function have been unsuccessful, an increasing number of preclinical and clinical trial
results highlight the significant impact of a plant-based diet through its modulatory
effect on the gut microbiome and the gut barrier in IBD. However, further research is
needed to evaluate the role of individual dietary components and complex dietary
interventions with anti-inflammatory potential in the prevention and treatment of IBD.
The high levels of prebiotic food components in a plant-rich diet are of particular
importance in the treatment of intestinal barrier disorders and the microbiome.
Preclinical and clinical studies highlight the modulatory effect of berries, especially
blueberries (Vaccinium myrtillus), on the microbiome, gut health and inflammation due to
their richness in prebiotically active polyphenols, flavonoids, anthocyanins and fiber.
However, the influence of blueberries on the intestinal barrier and the microbiome in
colitis patients has not yet been investigated. Mechanistically oriented clinical studies
are needed to confirm the prebiotic and preclinical findings in the clinic. Through a
targeted combination of clinical testing on patients, ex vivo examination of biopsy
material and cell biological studies at protein and transcriptome level, it should be
possible to develop a comprehensive picture of the influence of a blueberry-rich diet,
but also of the underlying pathomechanisms affected.
Aim of the study:
Determination of the influence of a three-month blueberry-rich diet compared to a diet
with a low blueberry content on disease activity, intestinal inflammation and symptoms in
patients with chronic colitis - initiated as part of a routine inpatient stay during
which patients are treated with a comprehensive multimodal integrative therapy concept
with dietary changes.
Exploratory study design:
This is an exploratory, prospective, monocentric, randomized, crossover study. 60 IBD
patients are randomized into two groups of 30 subjects each. During a period of 6 months,
which follows the inpatient-initiated integrative medical lifestyle modification program,
participants undergo two consecutive phases of 3 months each marked by a blueberry-rich
and a blueberry-poor diet. Dependent on the study group, half of the study participants
start the supplementary blueberry intake directly after the inpatient stay, the second
half three months later (cross-over principle).
Before the start of the study (W0), the colon of the participants is initially examined
for macroscopic inflammation and for intestinal barrier disorders using confocal laser
endomicroscopy as part of regular inpatient care. In order to investigate the influence
of the integrative therapy with or without blueberry intake on the intestinal barrier and
colonic inflammation, this will be checked after the end of the first 3 months (W12) and
after 6 months (W24) in a voluntary control sigmoidoscopy with confocal laser
endomicroscopy (CLE) as part of a short inpatient stay.
During the endoscopy, biopsies, bile, stool, urine and blood samples important for the
study are taken for examination. These serve to clarify mechanistic relationships between
the intestinal barrier function, the microbiome, its metabolic products (metabolome), the
immune system, the oxidative stress profile, the antioxidative capacity and the
inflammatory process (inflammation markers, immune cells and cytokines). In addition,
participants will receive questionnaires at all three time points (W0, W12, W24) to
evaluate their IBD-specific and general quality of life, symptoms, disease activity,
fatigue and stress levels.