Clinical trial NCT05971992: INulin-type Fructans-induced Gut Microbiota Modulation Impact on GUT-SKIN Axis Parameters in Psoriasis
Official title: Effect of Intestinal Microbiota Modulation Induced by the Chicory Inulin-type β-fructans on Metabolic Parameters and Biomarkers of the Gut-skin Axis in Chronic Skin Inflammation
Study type: INTERVENTIONAL
Overall status: ENROLLING_BY_INVITATION
Phase: NA
Conditions: Psoriasis
Keywords: prebiotics
inulin-type fructans
chronic skin inflammation
inflammatory mediators and cytokines
intestinal barrier permeability
Psoriasis Area and Severity Index
dysbiosis
metabolic dysregulation
nutritional status
anthropometric indices
indirect respirometry
functional multi-sugars absorption test
quality of life
characteristics of gut microbiota
short-chain fatty acids
immunohistological skin analysis
gene expression
oxidative stress
volatile organic compounds
Lead sponsor: Polish Academy of Sciences
Sponsor class: OTHER
Collaborators: name: University of Warmia and Mazury
name: Warsaw University of Life Sciences
First posted: 2023-08-02
Enrollment: 100
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: BASIC_SCIENCE

Brief summary: There is increasing evidence of a strong, bidirectional correlation between the gut and the skin, that associates gastrointestinal health with skin homeostasis and allostasis. The dysregulation in the intestinal microbiome-host interplay is connected with the development of many chronic skin inflammations.

Plaque psoriasis is a chronic, immune-mediated non-communicable dermatitis affecting approximately 2-3% of the world's population, regardless of gender and age. In most cases (about 70-80%), the skin lesions are mild and do not require systemic treatment. Its etiology is not fully understood, but apart from the genetic predisposition, it is strongly associated with the "gut-skin axis". The rise of the local and systemic immune response in psoriasis is a consequence of systemic inflammation due to intestinal dysbiosis associated with increased intestinal permeability. Thus, gut microbiota modulation should become a research target due to its great potential to impact inflammation, including skin dermatitis, and its manifested consequences.

Diet is an underestimated element in psoriasis management, meanwhile, the dietary ingredients support skin health. Among them, prebiotics favorably alters the composition and activity of the intestinal microbes and alleviates inflammation in the intestines. It was hypothesized that restoring the balance of the gut microbiome and the proper functioning of the intestinal barrier in subjects with psoriasis will alleviate the inflammatory symptoms and skin lesions observed in this chronic dermatitis.

The goal of this clinical trial is to determine if a diet supplementation with prebiotic (chicory-derived inulin-type β-fructans; ITFs) vs. placebo (maltodextrin) will induce health-related benefits in a mild degree PS, and determine if the identified benefits are evoked by compositional and/or functional shifts of the intestinal bacterial communities. Healthy individuals will constitute a control group (C).

Detailed description: The gut microbiota contributes to the health of the host. It enables the digestion of food, the proper functioning of the immune system, and protection against the invasion of pathogens. The gut microorganisms play a key role in maintaining the integrity of the intestinal epithelium. The epithelium serves as a selective barrier that, on the one hand, separates the immune cells of the intestinal mucosa from the microorganisms present in the lumen of the gut, and at the same time allows microbial metabolites to interact with the host cells and thus regulate the immune response. Dysbiosis of the intestinal microflora may result in damage to the intestinal integrity and, consequently, an increase in the permeability of the intestinal barrier. The translocation of bacterial antigens and metabolites into the bloodstream contributes to the activation of the local and systemic immune response resulting in local and systemic inflammation. Disruption of the interaction between the gut microbiome and the host can lead to inflammation. Plaque psoriasis is a chronic, immune-mediated dermatitis. It is manifested by peeling, itching, and reddening of the skin. Psoriasis is a non-communicable disease affecting approximately 2-3% of the world's population, regardless of gender and age. In most cases (about 70-80%), the skin lesions are mild and do not require systemic treatment. The etiology of psoriasis development is not fully understood. In addition to genetic predisposition, the increased immune response in PS may be a consequence of systemic inflammation due to intestinal dysbiosis associated with increased intestinal permeability.

Dietary ingredients support skin health. Among them, prebiotics gained our special interest as ingredients with proven beneficial effects on host health by modulating gut microflora. Inulin-type fructans derived from chicory are prebiotics that favorably alters the composition and activity of the intestinal microbes and alleviates the inflammation in the intestines. The investigators supposed that restoring the balance of the gut microbiota and the proper functioning of the intestinal barrier in subjects with psoriasis will alleviate the inflammatory symptoms and skin lesions observed in this chronic dermatitis. The aim of the research is to determine whether dietary supplementation with inulin-type β-fructans derived from chicory will transfer health benefits to individuals with psoriasis and to investigate whether these benefits are due to modification of the composition or activity of the gut microbiota.

To achieve this goal, the original, advanced, and complex studies were proposed on subjects with psoriasis to investigate the effects of dietary inulin-type fructans on the characteristics of the gut microflora, metabolic parameters, and biomarkers of the skin-gut axis. The obtained results will provide new knowledge and explain the nature of the interaction between the gut microbiota and the skin, providing further clues about the functioning of the gut-skin axis.

Eligibility criteria: Inclusion Criteria for PS patients:

* mild psoriasis (PASI \< 10),
* omnivorous diet,
* body mass index (BMI) 18 - 30 kg/m2
* general good health
* willing to give the written informed consent to participate the study

Exclusion Criteria for PS patients:

* other chronic or acute inflammatory skin diseases,
* gastrointestinal disease, cancer, cardiovascular complications, heart, kidney, and liver failure,
* bad or average overall health,
* positive tTG antibodies,
* currently receive anti-psoriatic systemic and biologic treatment,
* received antibiotics within previous month,
* use of dietary supplements containing probiotic, prebiotic, and/or symbiotic within previous month,
* Pregnancy, lactation

Primary outcomes:
measure: Concentration of inflammatory mediators
timeFrame: 24 months
Secondary outcomes:
measure: Assessment of the score of the psoriasis area and severity index (PASI)
timeFrame: 24 months
measure: Determination of the body mass index
timeFrame: 24 months
measure: Analysis of the concentration of anti-tissue transglutaminase antibodies
timeFrame: 24 months
measure: Analysis of the body composition
timeFrame: 24 months
measure: Analysis of the concentration of C-reactive protein (CRP)
timeFrame: 24 months
measure: Assessment of liver functions
timeFrame: 24 months
measure: Analysis of the concentration of creatinine
timeFrame: 24 months
measure: Determination of carbohydrate metabolism
timeFrame: 24 months
measure: Determination of lipids metabolism
timeFrame: 24 months
measure: Metabolic rate analysis
timeFrame: 24 months
measure: Assessment of qualitative and quantitative changes in the intestinal microbiota
timeFrame: 24 months
measure: Assessment of the metabolic activity of intestinal microbiota
timeFrame: 24 months
measure: Determination of changes in the expression of genes of inflammatory response in skin
timeFrame: 24 months
measure: Immunohistological skin analysis
timeFrame: 24 months
measure: Determination of the concentration of biomarkers of intestinal barrier permeability and integrity
timeFrame: 24 months
measure: Determination of the activity of oxidative stress parameters
timeFrame: 24 months
measure: Qualitative characteristics of volatile organic compounds
timeFrame: 24 months
measure: Determination of the nutritional status
timeFrame: 24 months
Other outcomes:
Locations:
city: Olsztyn
country: Poland
facility: Chair and Clinic of Dermatology, Sexually Transmitted Diseases and Clinical Immunology, Municipal Hospital Complex, al. Wojska Polskiego 30
city: Olsztyn
country: Poland
facility: Institute of Animal Reproduction and Food Research, Polish Academy of Sciences, ul. Tuwima 10
Study officials:
affiliation: Institute of Animal Reproduction and Food Research of Polish Academy of Sciences in Olsztyn, Poland
name: Urszula Krupa-Kozak, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Faculty of Medical Sciences of the University of Warmia and Mazury in Olsztyn, Poland
name: Agnieszka Owczarczyk-Saczonek, Prof
role: PRINCIPAL_INVESTIGATOR
affiliation: Institute of Human Nutrition Sciences, Warsaw University Of Life Sciences (SGGW), Poland
name: Ewa Lange, PhD
role: PRINCIPAL_INVESTIGATOR
References: