xml: <clinical_study>
    <!-- This xml conforms to an XML Schema at:
      https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
    <required_header>
      <download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
      <link_text>Link to the current ClinicalTrials.gov record.</link_text>
      <url>https://clinicaltrials.gov/ct2/show/NCT05971992</url>
    </required_header>
    <id_info>
      <org_study_id>2022/45/B/NZ9/03004</org_study_id>
      <nct_id>NCT05971992</nct_id>
    </id_info>
    <brief_title>INulin-type Fructans-induced Gut Microbiota Modulation Impact on GUT-SKIN Axis Parameters in Psoriasis</brief_title>
    <acronym>INGUTSKIN</acronym>
    <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</official_title>
    <sponsors>
      <lead_sponsor>
        <agency>Polish Academy of Sciences</agency>
        <agency_class>Other</agency_class>
      </lead_sponsor>
      <collaborator>
        <agency>University of Warmia and Mazury</agency>
        <agency_class>Other</agency_class>
      </collaborator>
      <collaborator>
        <agency>Warsaw University of Life Sciences</agency>
        <agency_class>Other</agency_class>
      </collaborator>
    </sponsors>
    <source>Polish Academy of Sciences</source>
    <oversight_info>
      <is_fda_regulated_drug>No</is_fda_regulated_drug>
      <is_fda_regulated_device>No</is_fda_regulated_device>
    </oversight_info>
    <brief_summary>
      <textblock>
        There is increasing evidence of a strong, bidirectional correlation between the gut and the&#xD;
        skin, that associates gastrointestinal health with skin homeostasis and allostasis. The&#xD;
        dysregulation in the intestinal microbiome-host interplay is connected with the development&#xD;
        of many chronic skin inflammations.&#xD;
  &#xD;
        Plaque psoriasis is a chronic, immune-mediated non-communicable dermatitis affecting&#xD;
        approximately 2-3% of the world's population, regardless of gender and age. In most cases&#xD;
        (about 70-80%), the skin lesions are mild and do not require systemic treatment. Its etiology&#xD;
        is not fully understood, but apart from the genetic predisposition, it is strongly associated&#xD;
        with the &quot;gut-skin axis&quot;. The rise of the local and systemic immune response in psoriasis is&#xD;
        a consequence of systemic inflammation due to intestinal dysbiosis associated with increased&#xD;
        intestinal permeability. Thus, gut microbiota modulation should become a research target due&#xD;
        to its great potential to impact inflammation, including skin dermatitis, and its manifested&#xD;
        consequences.&#xD;
  &#xD;
        Diet is an underestimated element in psoriasis management, meanwhile, the dietary ingredients&#xD;
        support skin health. Among them, prebiotics favorably alters the composition and activity of&#xD;
        the intestinal microbes and alleviates inflammation in the intestines. It was hypothesized&#xD;
        that restoring the balance of the gut microbiome and the proper functioning of the intestinal&#xD;
        barrier in subjects with psoriasis will alleviate the inflammatory symptoms and skin lesions&#xD;
        observed in this chronic dermatitis.&#xD;
  &#xD;
        The goal of this clinical trial is to determine if a diet supplementation with prebiotic&#xD;
        (chicory-derived inulin-type β-fructans; ITFs) vs. placebo (maltodextrin) will induce&#xD;
        health-related benefits in a mild degree PS, and determine if the identified benefits are&#xD;
        evoked by compositional and/or functional shifts of the intestinal bacterial communities.&#xD;
        Healthy individuals will constitute a control group (C).&#xD;
      </textblock>
    </brief_summary>
    <detailed_description>
      <textblock>
        The gut microbiota contributes to the health of the host. It enables the digestion of food,&#xD;
        the proper functioning of the immune system, and protection against the invasion of&#xD;
        pathogens. The gut microorganisms play a key role in maintaining the integrity of the&#xD;
        intestinal epithelium. The epithelium serves as a selective barrier that, on the one hand,&#xD;
        separates the immune cells of the intestinal mucosa from the microorganisms present in the&#xD;
        lumen of the gut, and at the same time allows microbial metabolites to interact with the host&#xD;
        cells and thus regulate the immune response. Dysbiosis of the intestinal microflora may&#xD;
        result in damage to the intestinal integrity and, consequently, an increase in the&#xD;
        permeability of the intestinal barrier. The translocation of bacterial antigens and&#xD;
        metabolites into the bloodstream contributes to the activation of the local and systemic&#xD;
        immune response resulting in local and systemic inflammation. Disruption of the interaction&#xD;
        between the gut microbiome and the host can lead to inflammation. Plaque psoriasis is a&#xD;
        chronic, immune-mediated dermatitis. It is manifested by peeling, itching, and reddening of&#xD;
        the skin. Psoriasis is a non-communicable disease affecting approximately 2-3% of the world's&#xD;
        population, regardless of gender and age. In most cases (about 70-80%), the skin lesions are&#xD;
        mild and do not require systemic treatment. The etiology of psoriasis development is not&#xD;
        fully understood. In addition to genetic predisposition, the increased immune response in PS&#xD;
        may be a consequence of systemic inflammation due to intestinal dysbiosis associated with&#xD;
        increased intestinal permeability.&#xD;
  &#xD;
        Dietary ingredients support skin health. Among them, prebiotics gained our special interest&#xD;
        as ingredients with proven beneficial effects on host health by modulating gut microflora.&#xD;
        Inulin-type fructans derived from chicory are prebiotics that favorably alters the&#xD;
        composition and activity of the intestinal microbes and alleviates the inflammation in the&#xD;
        intestines. The investigators supposed that restoring the balance of the gut microbiota and&#xD;
        the proper functioning of the intestinal barrier in subjects with psoriasis will alleviate&#xD;
        the inflammatory symptoms and skin lesions observed in this chronic dermatitis. The aim of&#xD;
        the research is to determine whether dietary supplementation with inulin-type β-fructans&#xD;
        derived from chicory will transfer health benefits to individuals with psoriasis and to&#xD;
        investigate whether these benefits are due to modification of the composition or activity of&#xD;
        the gut microbiota.&#xD;
  &#xD;
        To achieve this goal, the original, advanced, and complex studies were proposed on subjects&#xD;
        with psoriasis to investigate the effects of dietary inulin-type fructans on the&#xD;
        characteristics of the gut microflora, metabolic parameters, and biomarkers of the skin-gut&#xD;
        axis. The obtained results will provide new knowledge and explain the nature of the&#xD;
        interaction between the gut microbiota and the skin, providing further clues about the&#xD;
        functioning of the gut-skin axis.&#xD;
      </textblock>
    </detailed_description>
    <overall_status>Enrolling by invitation</overall_status>
    <start_date type="Actual">February 2, 2023</start_date>
    <completion_date type="Anticipated">February 2027</completion_date>
    <primary_completion_date type="Anticipated">February 2025</primary_completion_date>
    <phase>N/A</phase>
    <study_type>Interventional</study_type>
    <has_expanded_access>No</has_expanded_access>
    <study_design_info>
      <allocation>Randomized</allocation>
      <intervention_model>Parallel Assignment</intervention_model>
      <primary_purpose>Basic Science</primary_purpose>
      <masking>Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)</masking>
    </study_design_info>
    <primary_outcome>
      <measure>Concentration of inflammatory mediators</measure>
      <time_frame>24 months</time_frame>
      <description>The concentration of cytokines and chemokines: interferon-γ, interleukins: 1β, 1ra, 2, 4, 5, 6, 7, 8, 9, 10, 12 (p70), 13, 15, 17A, and tumor necrosis factor-α will be analyzed in blood using dedicated assay kit (Bio-Plex Pro Human Cytokine Assay; Bio-Rad)</description>
    </primary_outcome>
    <secondary_outcome>
      <measure>Assessment of the score of the psoriasis area and severity index (PASI)</measure>
      <time_frame>24 months</time_frame>
      <description>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).</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Determination of the body mass index</measure>
      <time_frame>24 months</time_frame>
      <description>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</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Analysis of the concentration of anti-tissue transglutaminase antibodies</measure>
      <time_frame>24 months</time_frame>
      <description>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.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Analysis of the body composition</measure>
      <time_frame>24 months</time_frame>
      <description>Body composition (percentage of total body fat, water, fat-free mass) will be assessed using a bioelectrical impedance analyser</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Analysis of the concentration of C-reactive protein (CRP)</measure>
      <time_frame>24 months</time_frame>
      <description>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</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Assessment of liver functions</measure>
      <time_frame>24 months</time_frame>
      <description>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.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Analysis of the concentration of creatinine</measure>
      <time_frame>24 months</time_frame>
      <description>The concentration of creatinine will be analyzed in urine according to standard procedures in the outpatient clinic of the Municipal Hospital in Olsztyn.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Determination of carbohydrate metabolism</measure>
      <time_frame>24 months</time_frame>
      <description>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.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Determination of lipids metabolism</measure>
      <time_frame>24 months</time_frame>
      <description>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.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Metabolic rate analysis</measure>
      <time_frame>24 months</time_frame>
      <description>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.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Assessment of qualitative and quantitative changes in the intestinal microbiota</measure>
      <time_frame>24 months</time_frame>
      <description>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.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Assessment of the metabolic activity of intestinal microbiota</measure>
      <time_frame>24 months</time_frame>
      <description>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.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Determination of changes in the expression of genes of inflammatory response in skin</measure>
      <time_frame>24 months</time_frame>
      <description>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</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Immunohistological skin analysis</measure>
      <time_frame>24 months</time_frame>
      <description>The concentration of tumor necrosis factor-α, 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.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Determination of the concentration of biomarkers of intestinal barrier permeability and integrity</measure>
      <time_frame>24 months</time_frame>
      <description>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, β-defensin-2, α1-Antitrypsin, sIgA) samples.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Determination of the activity of oxidative stress parameters</measure>
      <time_frame>24 months</time_frame>
      <description>Superoxide dismutase activity and catalase activity will be analyzed in blood serum</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Qualitative characteristics of volatile organic compounds</measure>
      <time_frame>24 months</time_frame>
      <description>The profile of volatile organic compounds will be determined by headspace microextraction coupled with gas-chromatography and mass spectrometry in urine and stool samples</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Determination of the nutritional status</measure>
      <time_frame>24 months</time_frame>
      <description>Nutritional status will be evaluated based on Food Frequency Questionnaire and a 3-days food record</description>
    </secondary_outcome>
    <number_of_arms>3</number_of_arms>
    <enrollment type="Anticipated">100</enrollment>
    <condition>Psoriasis</condition>
    <arm_group>
      <arm_group_label>Prebiotic</arm_group_label>
      <arm_group_type>Experimental</arm_group_type>
      <description>Adult women and men (N = 35) with mild psoriasis (Psoriasis Area and Severity Index; PASI &lt; 10) will receive 15g of prebiotic (chicory-derived inulin-type β-fructans) daily for 8 weeks</description>
    </arm_group>
    <arm_group>
      <arm_group_label>Placebo</arm_group_label>
      <arm_group_type>Placebo Comparator</arm_group_type>
      <description>Adult women and men (N = 35) with mild psoriasis (Psoriasis Area and Severity Index; PASI &lt; 10) will receive 15g of placebo (maltodextrin) daily for 8 weeks</description>
    </arm_group>
    <arm_group>
      <arm_group_label>Control</arm_group_label>
      <arm_group_type>No Intervention</arm_group_type>
      <description>Healthy adult women and men (N = 30) will not receive any dietary intervention</description>
    </arm_group>
    <intervention>
      <intervention_type>Dietary Supplement</intervention_type>
      <intervention_name>Chicory-derived inulin-type β-fructans</intervention_name>
      <description>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.</description>
      <arm_group_label>Prebiotic</arm_group_label>
      <other_name>Orafti®Synergy1 (Beneo, Tienen, Belgium)</other_name>
    </intervention>
    <intervention>
      <intervention_type>Dietary Supplement</intervention_type>
      <intervention_name>Maltodextrin</intervention_name>
      <description>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.</description>
      <arm_group_label>Placebo</arm_group_label>
    </intervention>
    <eligibility>
      <criteria>
        <textblock>
          Inclusion Criteria for PS patients:&#xD;
  &#xD;
            -  mild psoriasis (PASI &lt; 10),&#xD;
  &#xD;
            -  omnivorous diet,&#xD;
  &#xD;
            -  body mass index (BMI) 18 - 30 kg/m2&#xD;
  &#xD;
            -  general good health&#xD;
  &#xD;
            -  willing to give the written informed consent to participate the study&#xD;
  &#xD;
          Exclusion Criteria for PS patients:&#xD;
  &#xD;
            -  other chronic or acute inflammatory skin diseases,&#xD;
  &#xD;
            -  gastrointestinal disease, cancer, cardiovascular complications, heart, kidney, and&#xD;
               liver failure,&#xD;
  &#xD;
            -  bad or average overall health,&#xD;
  &#xD;
            -  positive tTG antibodies,&#xD;
  &#xD;
            -  currently receive anti-psoriatic systemic and biologic treatment,&#xD;
  &#xD;
            -  received antibiotics within previous month,&#xD;
  &#xD;
            -  use of dietary supplements containing probiotic, prebiotic, and/or symbiotic within&#xD;
               previous month,&#xD;
  &#xD;
            -  Pregnancy, lactation&#xD;
        </textblock>
      </criteria>
      <gender>All</gender>
      <minimum_age>18 Years</minimum_age>
      <maximum_age>65 Years</maximum_age>
      <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
    </eligibility>
    <overall_official>
      <last_name>Urszula Krupa-Kozak, PhD</last_name>
      <role>Principal Investigator</role>
      <affiliation>Institute of Animal Reproduction and Food Research of Polish Academy of Sciences in Olsztyn, Poland</affiliation>
    </overall_official>
    <overall_official>
      <last_name>Agnieszka Owczarczyk-Saczonek, Prof</last_name>
      <role>Principal Investigator</role>
      <affiliation>Faculty of Medical Sciences of the University of Warmia and Mazury in Olsztyn, Poland</affiliation>
    </overall_official>
    <overall_official>
      <last_name>Ewa Lange, PhD</last_name>
      <role>Principal Investigator</role>
      <affiliation>Institute of Human Nutrition Sciences, Warsaw University Of Life Sciences (SGGW), Poland</affiliation>
    </overall_official>
    <location>
      <facility>
        <name>Chair and Clinic of Dermatology, Sexually Transmitted Diseases and Clinical Immunology, Municipal Hospital Complex, al. Wojska Polskiego 30</name>
        <address>
          <city>Olsztyn</city>
          <zip>10-229</zip>
          <country>Poland</country>
        </address>
      </facility>
    </location>
    <location>
      <facility>
        <name>Institute of Animal Reproduction and Food Research, Polish Academy of Sciences, ul. Tuwima 10</name>
        <address>
          <city>Olsztyn</city>
          <zip>10-748</zip>
          <country>Poland</country>
        </address>
      </facility>
    </location>
    <location_countries>
      <country>Poland</country>
    </location_countries>
    <verification_date>July 2023</verification_date>
    <study_first_submitted>July 14, 2023</study_first_submitted>
    <study_first_submitted_qc>July 24, 2023</study_first_submitted_qc>
    <study_first_posted type="Actual">August 2, 2023</study_first_posted>
    <last_update_submitted>July 24, 2023</last_update_submitted>
    <last_update_submitted_qc>July 24, 2023</last_update_submitted_qc>
    <last_update_posted type="Actual">August 2, 2023</last_update_posted>
    <responsible_party>
      <responsible_party_type>Principal Investigator</responsible_party_type>
      <investigator_affiliation>Polish Academy of Sciences</investigator_affiliation>
      <investigator_full_name>Urszula Krupa-Kozak</investigator_full_name>
      <investigator_title>Principal Investigator</investigator_title>
    </responsible_party>
    <keyword>prebiotics</keyword>
    <keyword>inulin-type fructans</keyword>
    <keyword>chronic skin inflammation</keyword>
    <keyword>inflammatory mediators and cytokines</keyword>
    <keyword>intestinal barrier permeability</keyword>
    <keyword>Psoriasis Area and Severity Index</keyword>
    <keyword>dysbiosis</keyword>
    <keyword>metabolic dysregulation</keyword>
    <keyword>nutritional status</keyword>
    <keyword>anthropometric indices</keyword>
    <keyword>indirect respirometry</keyword>
    <keyword>functional multi-sugars absorption test</keyword>
    <keyword>quality of life</keyword>
    <keyword>characteristics of gut microbiota</keyword>
    <keyword>short-chain fatty acids</keyword>
    <keyword>immunohistological skin analysis</keyword>
    <keyword>gene expression</keyword>
    <keyword>oxidative stress</keyword>
    <keyword>volatile organic compounds</keyword>
    <condition_browse>
      <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
      <mesh_term>Psoriasis</mesh_term>
    </condition_browse>
    <patient_data>
      <sharing_ipd>No</sharing_ipd>
      <ipd_description>Research results presented as average (+/- SD) or median will be successively made available in the form of English-language scientific publications in the Open Access format published in international journals and/or presented in the form of conference reports.</ipd_description>
    </patient_data>
    <!-- Results have not yet been posted for this study                                          -->
  </clinical_study>
  
  
text: download date: ClinicalTrials.gov processed this data on September 20, 2023
  link text: Link to the current ClinicalTrials.gov record.
  url: https://clinicaltrials.gov/ct2/show/NCT05971992
  org study id: 2022/45/B/NZ9/03004
  nct id: NCT05971992
  lead sponsor: 
  collaborator: 
  collaborator: 
  is fda regulated drug: No
  is fda regulated device: No
  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).
  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.
  allocation: Randomized
  intervention model: Parallel Assignment
  primary purpose: Basic Science
  masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
  measure: Concentration of inflammatory mediators
  time frame: 24 months
  description: The concentration of cytokines and chemokines: interferon-γ, interleukins: 1β, 1ra, 2, 4, 5, 6, 7, 8, 9, 10, 12 (p70), 13, 15, 17A, and tumor necrosis factor-α will be analyzed in blood using dedicated assay kit (Bio-Plex Pro Human Cytokine Assay; Bio-Rad)
  measure: Assessment of the score of the psoriasis area and severity index (PASI)
  time frame: 24 months
  description: 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).
  measure: Determination of the body mass index
  time frame: 24 months
  description: 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
  measure: Analysis of the concentration of anti-tissue transglutaminase antibodies
  time frame: 24 months
  description: 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.
  measure: Analysis of the body composition
  time frame: 24 months
  description: Body composition (percentage of total body fat, water, fat-free mass) will be assessed using a bioelectrical impedance analyser
  measure: Analysis of the concentration of C-reactive protein (CRP)
  time frame: 24 months
  description: 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
  measure: Assessment of liver functions
  time frame: 24 months
  description: 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.
  measure: Analysis of the concentration of creatinine
  time frame: 24 months
  description: The concentration of creatinine will be analyzed in urine according to standard procedures in the outpatient clinic of the Municipal Hospital in Olsztyn.
  measure: Determination of carbohydrate metabolism
  time frame: 24 months
  description: 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.
  measure: Determination of lipids metabolism
  time frame: 24 months
  description: 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.
  measure: Metabolic rate analysis
  time frame: 24 months
  description: 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.
  measure: Assessment of qualitative and quantitative changes in the intestinal microbiota
  time frame: 24 months
  description: 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.
  measure: Assessment of the metabolic activity of intestinal microbiota
  time frame: 24 months
  description: 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.
  measure: Determination of changes in the expression of genes of inflammatory response in skin
  time frame: 24 months
  description: 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
  measure: Immunohistological skin analysis
  time frame: 24 months
  description: The concentration of tumor necrosis factor-α, 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.
  measure: Determination of the concentration of biomarkers of intestinal barrier permeability and integrity
  time frame: 24 months
  description: 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, β-defensin-2, α1-Antitrypsin, sIgA) samples.
  measure: Determination of the activity of oxidative stress parameters
  time frame: 24 months
  description: Superoxide dismutase activity and catalase activity will be analyzed in blood serum
  measure: Qualitative characteristics of volatile organic compounds
  time frame: 24 months
  description: The profile of volatile organic compounds will be determined by headspace microextraction coupled with gas-chromatography and mass spectrometry in urine and stool samples
  measure: Determination of the nutritional status
  time frame: 24 months
  description: Nutritional status will be evaluated based on Food Frequency Questionnaire and a 3-days food record
  arm group label: Prebiotic
  arm group type: Experimental
  description: Adult women and men (N = 35) with mild psoriasis (Psoriasis Area and Severity Index; PASI < 10) will receive 15g of prebiotic (chicory-derived inulin-type β-fructans) daily for 8 weeks
  arm group label: Placebo
  arm group type: Placebo Comparator
  description: Adult women and men (N = 35) with mild psoriasis (Psoriasis Area and Severity Index; PASI < 10) will receive 15g of placebo (maltodextrin) daily for 8 weeks
  arm group label: Control
  arm group type: No Intervention
  description: Healthy adult women and men (N = 30) will not receive any dietary intervention
  intervention type: Dietary Supplement
  intervention name: Chicory-derived inulin-type β-fructans
  description: 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.
  arm group label: Prebiotic
  other name: Orafti®Synergy1 (Beneo, Tienen, Belgium)
  intervention type: Dietary Supplement
  intervention name: Maltodextrin
  description: 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.
  arm group label: Placebo
  criteria: 
  gender: All
  minimum age: 18 Years
  maximum age: 65 Years
  healthy volunteers: Accepts Healthy Volunteers
  last name: Urszula Krupa-Kozak, PhD
  role: Principal Investigator
  affiliation: Institute of Animal Reproduction and Food Research of Polish Academy of Sciences in Olsztyn, Poland
  last name: Agnieszka Owczarczyk-Saczonek, Prof
  role: Principal Investigator
  affiliation: Faculty of Medical Sciences of the University of Warmia and Mazury in Olsztyn, Poland
  last name: Ewa Lange, PhD
  role: Principal Investigator
  affiliation: Institute of Human Nutrition Sciences, Warsaw University Of Life Sciences (SGGW), Poland
  facility: 
  facility: 
  country: Poland
  responsible party type: Principal Investigator
  investigator affiliation: Polish Academy of Sciences
  investigator full name: Urszula Krupa-Kozak
  investigator title: Principal Investigator
  mesh term: Psoriasis
  sharing ipd: No
  ipd description: Research results presented as average (+/- SD) or median will be successively made available in the form of English-language scientific publications in the Open Access format published in international journals and/or presented in the form of conference reports.