INulin-type Fructans-induced Gut Microbiota Modulation Impact on GUT-SKIN Axis Parameters in Psoriasis

Psoriasis Clinical Trial

— INGUTSKIN  

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

Clinical Trial Details — Status: Enrolling by invitation

Administrative data

• NCT number: NCT05971992
• Other study ID #: 2022/45/B/NZ9/03004
• Status: Enrolling by invitation
• Phase: N/A
• Start date: February 2, 2023
• Est. completion date: February 2027

Study information

• Verified date: July 2023
• Source: Polish Academy of Sciences
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

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.

Recruitment information / eligibility

• Status: Enrolling by invitation
• Enrollment: 100
• Est. completion date: February 2027
• Est. primary completion date: February 2025
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 65 Years

Eligibility

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

Related Conditions & MeSH terms

• Psoriasis

Intervention

Dietary Supplement:
• Chicory-derived inulin-type ß-fructans
This supplement will be portioned into moisture-impermeable sachets containing 7.5 grams of prebiotic. During the first two weeks, to avoid eventual side effects, PS participants will be advised to consume the contents of one sachet at breakfast only. Starting in week 3 until the end of the 8-weeks intervention the participants will consume the content of two sachets daily (at breakfast and at dinner) resulting in a total dose of 15 grams of prebiotic per day. Participants will be provided with a package of sachets in the amount required for the whole 8-weeks nutritional intervention. They will be instructed to dissolve the sachet content with water or juice and to drink it 15-20 minutes prior to their regular meal. The medium for suspending the supplement (water or juice) could be chosen by the participants and could be changed during the study.
• Maltodextrin
This supplement will be portioned into moisture-impermeable sachets containing 7.5 grams of maltodextrin. During the first two weeks, to avoid eventual side effects, PS participants will be advised to consume the contents of one sachet at breakfast only. Starting in week 3 until the end of the 8-week intervention the participants will consume the content of two sachets daily (at breakfast and at dinner) resulting in a total dose of 15 grams of placebo per day. Participants will be provided with a package of sachets in the amount required for the whole 8-weeks nutritional intervention. They will be instructed to dissolve the sachet content with water or juice and to drink it 15-20 minutes prior to their regular meal. The medium for suspending the supplement (water or juice) could be chosen by the participants and could be changed during the study.

Locations

Country	Name	City	State
Poland	Chair and Clinic of Dermatology, Sexually Transmitted Diseases and Clinical Immunology, Municipal Hospital Complex, al. Wojska Polskiego 30	Olsztyn
Poland	Institute of Animal Reproduction and Food Research, Polish Academy of Sciences, ul. Tuwima 10	Olsztyn

Sponsors (3)

Lead Sponsor	Collaborator
Polish Academy of Sciences	University of Warmia and Mazury, Warsaw University of Life Sciences

Country where clinical trial is conducted

Poland, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Concentration of inflammatory mediators	The concentration of cytokines and chemokines: interferon-?, interleukins: 1ß, 1ra, 2, 4, 5, 6, 7, 8, 9, 10, 12 (p70), 13, 15, 17A, and tumor necrosis factor-a will be analyzed in blood using dedicated assay kit (Bio-Plex Pro Human Cytokine Assay; Bio-Rad)	24 months
Secondary	Assessment of the score of the psoriasis area and severity index (PASI)	The psoriasis area and severity index (PASI) combines the assessment of the severity of and area affected by psoriasis into a single score in the range 0 (no disease) to 72 (maximal disease).	24 months
Secondary	Determination of the body mass index	The body height (in meters) and body weight (in kilograms) will be measeure and will be combined to report body mass index (BMI) in kg/m^2	24 months
Secondary	Analysis of the concentration of anti-tissue transglutaminase antibodies	The concentration of anti-tissue transglutaminase antibodiesanty-tTG will be determined in blood serum according to standard procedures in the outpatient clinic of the Municipal Hospital in Olsztyn.	24 months
Secondary	Analysis of the body composition	Body composition (percentage of total body fat, water, fat-free mass) will be assessed using a bioelectrical impedance analyser	24 months
Secondary	Analysis of the concentration of C-reactive protein (CRP)	The concentration of the C-reactive protein (CRP) will be analyzed according to standard procedures in the outpatient clinic of the Municipal Hospital in Olsztyn. Serum anty-tTG will be determined to exclude the gluten-related disorders	24 months
Secondary	Assessment of liver functions	The concentration of aspartate aminotransferase and alanine aminotransferase will be analyzed according to standard procedures in the outpatient clinic of the Municipal Hospital in Olsztyn.	24 months
Secondary	Analysis of the concentration of creatinine	The concentration of creatinine will be analyzed in urine according to standard procedures in the outpatient clinic of the Municipal Hospital in Olsztyn.	24 months
Secondary	Determination of carbohydrate metabolism	The concentration of glycated hemoglobin, glucose and insulin will be determined in fasting blood and analyzed according to standard procedures in the outpatient clinic of the Municipal Hospital in Olsztyn.	24 months
Secondary	Determination of lipids metabolism	The concentration of apolipoproteins A and B will be determined in fasting blood and analyzed according to standard procedures in the outpatient clinic of the Municipal Hospital in Olsztyn.	24 months
Secondary	Metabolic rate analysis	The resting energy expenditure will be measured by indirect respirometry with ventilated open-circuit (with canopy system) using Cosmed K5 mobile device, in conditions of thermal comfort, under fasting conditions, and in the supine position. Determining the volume of oxygen and carbon dioxide enables the determination of respiratory quotients and the degree of utilization of fat and carbohydrates in the body.	24 months
Secondary	Assessment of qualitative and quantitative changes in the intestinal microbiota	The hyper-variable regions of the 16S rRNA bacterial gene (V3-V8) will be amplified. Bacterial libraries will be created using a Ligation Sequencing Kit 1D plus either Native Barcoding Expansion or a set of custom barcodes. Final libraries will be sequenced on a GridION X5 sequencer (Oxford Nanopore Technologies, Oxford, UK). High-quality reads will be processed for taxonomic identification by matching the NGS sequences with sequences deposited in the NCBI using a modified uSEARCH algorithm.	24 months
Secondary	Assessment of the metabolic activity of intestinal microbiota	The concentration and profile of short-chain fatty acids (SCFA) will be analyzed using the gas chromatograph with a flame-ionization detector and the autosampler in stool samples collected from patients after nutritional intervention with prebiotic or placebo.	24 months
Secondary	Determination of changes in the expression of genes of inflammatory response in skin	Changes in the expression of genes of inflammatory response will be determined by real-time PCR in skin biopsies collected from patients after nutritional intervention with prebiotic or placebo	24 months
Secondary	Immunohistological skin analysis	The concentration of tumor necrosis factor-a, interleukins 17A, 17F, 12, 23, 8, 22, 35, and interferon-gamma will be determined in lesional and non-lesional skin specimens collected from study participants.	24 months
Secondary	Determination of the concentration of biomarkers of intestinal barrier permeability and integrity	The concentration of the selected intestinal barrier permeability and integrity biomarkers will be analyzed using the ELISA method in the blood (zonulin, iFABP, claudin-3, bacterial LPS) and in stool (calprotectin, ß-defensin-2, a1-Antitrypsin, sIgA) samples.	24 months
Secondary	Determination of the activity of oxidative stress parameters	Superoxide dismutase activity and catalase activity will be analyzed in blood serum	24 months
Secondary	Qualitative characteristics of volatile organic compounds	The profile of volatile organic compounds will be determined by headspace microextraction coupled with gas-chromatography and mass spectrometry in urine and stool samples	24 months
Secondary	Determination of the nutritional status	Nutritional status will be evaluated based on Food Frequency Questionnaire and a 3-days food record	24 months