<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/NCT03800147</url>
  </required_header>
  <id_info>
    <org_study_id>FAT Study</org_study_id>
    <nct_id>NCT03800147</nct_id>
  </id_info>
  <brief_title>Effects of Nutritional Fat on the Growth of Intestinal E. Coli</brief_title>
  <official_title>Effects of Nutritional Fat on the Growth of Intestinal E. Coli</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University of Zurich</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>University of Zurich</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
    <is_us_export>No</is_us_export>
  </oversight_info>
  <brief_summary>
    <textblock>
      Recent experiments in the lab of Prof. WD Hardt revealed, that in mice, 24 h exposure to a&#xD;
      high-fat diet results in a breakdown of colonization resistance against Salmonella&#xD;
      typhimurium. Mechanistic experiments identified bile acids as the mediator for reduced&#xD;
      colonization resistance. Exposure to a high fat diet leads to increased bile acid secretion&#xD;
      which in turn modify the intestinal microbiota.&#xD;
&#xD;
      It is now the aim to verify the results of this study in human healthy volunteers. The&#xD;
      nutritional habits of all participants will carefully be evaluated. In the intervention&#xD;
      phase, participants will be exposed to either high-fat or low-fat diet and a controlled dose&#xD;
      of the non-pathogenic bacteria E. coli Nissle. E. coli Nissle is the active compound for&#xD;
      &quot;Mutaflor®&quot; and other probiotics.&#xD;
&#xD;
      It is planned to enumerate E. coli Nissle counts in the stool after Mutaflor ingestion and to&#xD;
      quantify other changes of the human microbiota. The hypothesis is that a high-fat diet leads&#xD;
      to increased bile acid secretion results in favorable growth conditions for E. coli Nissle,&#xD;
      resulting in high bacterial counts in the stool.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Infectious diarrhea causes substantial morbidity in Western countries and the developing&#xD;
      world and leads to the use of considerable health resources. Antibiotic resistance continues&#xD;
      to increase, potentially leading to a decrease in therapeutic options in the future.&#xD;
      Important pathogens include Salmonella typhimurium (S. typhimurium) and pathogenic&#xD;
      Escherichia coli (E. coli) which are genetically closely related.&#xD;
&#xD;
      The human intestine has considerable colonization resistance against bacterial pathogens.&#xD;
      This resistance is largely mediated by the gut microbiota. Therefore, previous exposure to&#xD;
      antibiotics or immunosuppression leading to a breakdown of the intestinal defense systems&#xD;
      increase the risk for subsequent infection with S. typhimurium.&#xD;
&#xD;
      The composition of the human microbiome undergoes dramatic changes upon exposure to various&#xD;
      factors including nutrition, physical activity, drugs and much more. Most studies focused on&#xD;
      long-term exposure to various factors; however, since bacterial growth is rapid (doubling&#xD;
      time of S. typhimurium under optimal conditions = 20min), even short-term variations in the&#xD;
      environment could dramatically influence the human microbiota.&#xD;
&#xD;
      In the lab of Prof. WD Hardt, a mouse model of S. typhimurium enterocolitis has been&#xD;
      established. Since most mouse strains are resistant against colonization with S. typhimurium,&#xD;
      pretreatment with antibiotics is a requirement for induction of S. typhimurium enterolitis.&#xD;
      However, recent experiments in the Hardt lab revealed, that in mice, 24 h exposure to a&#xD;
      high-fat diet also results in a breakdown of colonization resistance, leading to Salmonella&#xD;
      enterocolitis upon S. typhimurium infection. The same is true for E. coli strains. Subsequent&#xD;
      experiments demonstrated that exposure to fatty acids is sufficient to overcome colonization&#xD;
      resistance. Mechanistic experiments identified fat-elicited bile-release as the underlying&#xD;
      mechanism: Exposure to a high fat diet leads to increased bile acid secretion; S. typhimurium&#xD;
      can tolerate 10-fold higher bile acid concentrations than commensal bacterial, leading to a&#xD;
      growth advantage of S. typhimurium compared to competing bacteria (WD Hardt et al.,&#xD;
      unpublished data).&#xD;
&#xD;
      The aim of this study is to verify the results of this study in human healthy volunteers. The&#xD;
      nutritional habits of all participants will be carefully evaluated. In the intervention&#xD;
      phase, participants will be exposed to either high-fat or low-fat diet and a controlled dose&#xD;
      of the non-pathogenic bacteria E. coli Nissle. E. coli Nissle is the active compound for&#xD;
      &quot;Mutaflor®&quot; and other probiotics. E. coli Nissle has therapeutic effects for the treatment of&#xD;
      chronic inflammatory intestinal diseases. In contrast to other non-pathogenic E. coli&#xD;
      strains, it exhibits a specific pattern of fitness factors but lacks prominent virulence&#xD;
      factors. In vivo and in vitro experiments demonstrated both, protective effects against&#xD;
      infection with intestinal pathogens as well as potent immunomodulatory properties. Growth of&#xD;
      E. coli Nissle in the human gut resembles growth of S. typhimurium. Both bacteriae also share&#xD;
      metabolic requirements for intestinal growth. Therefore, growth E. coli Nissle in the human&#xD;
      intestine can be used as a marker for growth of E. coli strains, Salmonella typhimurium and&#xD;
      related pathogens.&#xD;
&#xD;
      It is planned to enumerate E. coli Nissle counts in the stool after Mutaflor ingestion and to&#xD;
      quantify other changes of the human microbiota. The hypothesize is that a high-fat diet,&#xD;
      leading to increased bile acid secretion results in favorable growth conditions for E. coli&#xD;
      Nissle, resulting in high bacterial counts in the stool.&#xD;
&#xD;
      The results of the study will help improving the understanding of the consequences of&#xD;
      nutritional composition on the vulnerability of the human organism to bacterial infections.&#xD;
      Such an improved understanding might enable designing preventive measures for the growth of&#xD;
      unwanted E. coli strains (e.g. ESBL, pathogenic) or S. typhimurium infection and/ or a severe&#xD;
      disease course and might ultimately help limiting antibiotic use and the evolution of&#xD;
      antibiotic resistant pathogens.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Not yet recruiting</last_known_status>
  <start_date type="Anticipated">January 24, 2019</start_date>
  <completion_date type="Anticipated">September 24, 2019</completion_date>
  <primary_completion_date type="Anticipated">September 24, 2019</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>Crossover Assignment</intervention_model>
    <intervention_model_description>randomized controlled crossover clinical study</intervention_model_description>
    <primary_purpose>Basic Science</primary_purpose>
    <masking>Single (Investigator)</masking>
    <masking_description>Participants will not be blinded regarding the composition of their nutrition. Investigators performing stool and blood analyses will be blinded to the group assignment of the participants.</masking_description>
  </study_design_info>
  <primary_outcome>
    <measure>Maximum concentration of E. coli Nissle bacteriae in all stool samples of each participant</measure>
    <time_frame>1, 2 and 5 days after E. coli Nissle inoculation</time_frame>
    <description>Each participant's fecal samples will be analyzed for E. coli Nissle bacteriae. Only the stool samples acquired in intervention phase 1 will be considered. For each participant, the maximum concentration of E. coli Nissle in all stool samples (assessed by qPCR) will be used for the calculation of the primary outcome.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Comparison of E. coli Nissle concentration in feces between high-fat diet and low-fat diet</measure>
    <time_frame>1, 2 and 5 days after E. coli Nissle inoculation</time_frame>
    <description>The concentration of E. coli Nissle bacteriae (CFU per g feces) in participants exposed to high-fat diet will be compared to the concentration of E. coli Nissle bacteriae in individuals exposed to low-fat diet (Mann-Whitney U test, a p-value &lt;0.05 will be considered significant).</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Chemical composition of blood</measure>
    <time_frame>Week 1 - 8</time_frame>
    <description>For each participant's blood samples the chemical composition including bile acids, lipids, cholesterol and other compounds related to fat, cholesterol and bile acid metabolism will be determined (concentration, per μl blood). Samples at baseline, during intervention phase and the washout phase will be analyzed. For each compound the group exposed to low-fat diet and high-fat diet will be compared, respectively (intervention phase) or the group with the lowest and highest fat ingestion according to the nutritional protocol.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Chemical composition of stool</measure>
    <time_frame>Week 1 - 8</time_frame>
    <description>For each participant's stool samples the chemical composition including bile acids, lipids, cholesterol and other compounds related to fat, cholesterol and bile acid metabolism will be determined (concentration, per g stool). Samples at baseline, during intervention phase and the washout phase will be analyzed. For each compound the group exposed to low-fat diet and high-fat diet will be compared, respectively (intervention phase) or the group with the lowest and highest fat ingestion according to the nutritional protocol.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Microbiota composition: taxonomic composition</measure>
    <time_frame>Week 1 - 8</time_frame>
    <description>Same as 4, only the microbiota taxonomic composition in stool samples will be analyzed by ribosomal RNA gene sequencing. Analysis will also include tests for microbiota diversity (i.e. number of bacteria species identified). Findings will be compared to changes occurring in the microbiota of participants in the other study group.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Microbiota composition: metagenomic properties</measure>
    <time_frame>Week 1 - 8</time_frame>
    <description>Same as 4, only the metagenomic properties of the microbiota in stool samples will be analyzed by whole genome shotgun sequencing. Analyses will also test for metabolic pathways used by the microbiota. Microbiological and molecular biology methods will also be used to characterize bacteria strains associated with high-fat diet, low-fat diet and/ or changes in bile acid concentration.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Microbiota composition: E. coli content</measure>
    <time_frame>Week 1 - 8</time_frame>
    <description>Same as 4, only the E. coli content of stool samples will be analyzed by sequencing and conventional plating techniques. This will quantify E. coli Nissle and also all endogenous E. coli strains present in the sample.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Antibody response against E. coli Nissle</measure>
    <time_frame>3 weeks after inoculation of E. coli Nissle</time_frame>
    <description>Antibody titers against E. coli Nissle will be determined by bacterial FACS or other appropriate techniques. Antibody titers at baseline, at 2 weeks and at 3 weeks will be determined. Individuals exposed to low-fat diet and high-fat diet will be compared. Measured variable: Antibody titers against E. coli Nissle and various E. coli strains.</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Anticipated">40</enrollment>
  <condition>Escherichia Coli Infections</condition>
  <arm_group>
    <arm_group_label>High-fat diet</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Participants will follow a high-fat diet. During the intervention phase, they will inoculate &quot;Mutaflor Suspension&quot; (E. coli Nissle 1917) (Single dose, 5 ml = 5x10^8 CFU).&#xD;
Blood samples, stool samples and clinical information will be collected during the study.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Low-fat diet</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Participants will follow a low-fat diet. During the intervention phase, they will inoculate &quot;Mutaflor Suspension&quot; (E. coli Nissle 1917) (Single dose, 5 ml = 5x10^8 CFU).&#xD;
Blood samples, stool samples and clinical information will be collected during the study.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>&quot;Mutaflor Suspension&quot; (E. coli Nissle 1917)</intervention_name>
    <description>Inoculation of &quot;Mutaflor Suspension&quot; (E. coli Nissle 1917)</description>
    <arm_group_label>High-fat diet</arm_group_label>
    <arm_group_label>Low-fat diet</arm_group_label>
    <other_name>Mutaflor Suspension</other_name>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Blood samples</intervention_name>
    <description>Blood samples will be collected and analyzed at different study time points</description>
    <arm_group_label>High-fat diet</arm_group_label>
    <arm_group_label>Low-fat diet</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Stool samples</intervention_name>
    <description>Stool samples will be collected and analyzed at different study time points</description>
    <arm_group_label>High-fat diet</arm_group_label>
    <arm_group_label>Low-fat diet</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Clinical information</intervention_name>
    <description>Clinical information will be collected at different study time points using questionnaires</description>
    <arm_group_label>High-fat diet</arm_group_label>
    <arm_group_label>Low-fat diet</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Individuals free of abdominal complaints or symptoms&#xD;
&#xD;
          -  Written informed consent&#xD;
&#xD;
          -  Age 18 - 85 years&#xD;
&#xD;
          -  Working at ETH Zurich or University of Zurich and trained and experienced in handling&#xD;
             -80°C freezers at biosafety level 2.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Previous history of gastrointestinal disease or surgery (excludes appendectomy, hernia&#xD;
             repair and surgery for anorectal disorders)&#xD;
&#xD;
          -  Known diabetes mellitus, scleroderma, neurological impairment or other major diseases&#xD;
             requiring ongoing management&#xD;
&#xD;
          -  Immunesuppression&#xD;
&#xD;
          -  Subjects with antibiotic therapy, proton pump inhibitors or laxatives within the last&#xD;
             four weeks&#xD;
&#xD;
          -  Pregnancy beyond week 12. &quot;Mutaflor&quot; intake is safe during pregnancy; however, special&#xD;
             regulations are required to gain access to the -80°C freezers. No pregnancy test will&#xD;
             be performed.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>85 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Wolf-Dietrich Hardt, Prof. Dr.</last_name>
    <role>Principal Investigator</role>
    <affiliation>ETH Zurich, Institute of Microbiology</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Benjamin Misselwitz, MD</last_name>
    <phone>+41 44 255 1111</phone>
    <email>benjamin.misselwitz@usz.ch</email>
  </overall_contact>
  <overall_contact_backup>
    <last_name>Wolf-Dietrich Hardt, Prof. Dr.</last_name>
    <phone>+41 44 632 51 43</phone>
    <email>hardt@micro.biol.ethz.ch</email>
  </overall_contact_backup>
  <location>
    <facility>
      <name>Institute of Microbiology (D-BIOL), ETH Zurich</name>
      <address>
        <city>Zürich</city>
        <zip>8093</zip>
        <country>Switzerland</country>
      </address>
    </facility>
    <contact>
      <last_name>Wolf-Dietrich Hardt, Prof. Dr.</last_name>
      <phone>+41446325143</phone>
      <phone_ext>+41446325143</phone_ext>
      <email>hardt@micro.biol.ethz.ch</email>
    </contact>
  </location>
  <location_countries>
    <country>Switzerland</country>
  </location_countries>
  <verification_date>January 2019</verification_date>
  <study_first_submitted>December 13, 2018</study_first_submitted>
  <study_first_submitted_qc>January 7, 2019</study_first_submitted_qc>
  <study_first_posted type="Actual">January 11, 2019</study_first_posted>
  <last_update_submitted>January 7, 2019</last_update_submitted>
  <last_update_submitted_qc>January 7, 2019</last_update_submitted_qc>
  <last_update_posted type="Actual">January 11, 2019</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Escherichia coli Infections</mesh_term>
  </condition_browse>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


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/NCT03800147
org study id: FAT Study
nct id: NCT03800147
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
is us export: No
Recent experiments in the lab of Prof. WD Hardt revealed, that in mice, 24 h exposure to a
      high-fat diet results in a breakdown of colonization resistance against Salmonella
      typhimurium. Mechanistic experiments identified bile acids as the mediator for reduced
      colonization resistance. Exposure to a high fat diet leads to increased bile acid secretion
      which in turn modify the intestinal microbiota.

      It is now the aim to verify the results of this study in human healthy volunteers. The
      nutritional habits of all participants will carefully be evaluated. In the intervention
      phase, participants will be exposed to either high-fat or low-fat diet and a controlled dose
      of the non-pathogenic bacteria E. coli Nissle. E. coli Nissle is the active compound for
      "Mutaflor®" and other probiotics.

      It is planned to enumerate E. coli Nissle counts in the stool after Mutaflor ingestion and to
      quantify other changes of the human microbiota. The hypothesis is that a high-fat diet leads
      to increased bile acid secretion results in favorable growth conditions for E. coli Nissle,
      resulting in high bacterial counts in the stool.
Infectious diarrhea causes substantial morbidity in Western countries and the developing
      world and leads to the use of considerable health resources. Antibiotic resistance continues
      to increase, potentially leading to a decrease in therapeutic options in the future.
      Important pathogens include Salmonella typhimurium (S. typhimurium) and pathogenic
      Escherichia coli (E. coli) which are genetically closely related.

      The human intestine has considerable colonization resistance against bacterial pathogens.
      This resistance is largely mediated by the gut microbiota. Therefore, previous exposure to
      antibiotics or immunosuppression leading to a breakdown of the intestinal defense systems
      increase the risk for subsequent infection with S. typhimurium.

      The composition of the human microbiome undergoes dramatic changes upon exposure to various
      factors including nutrition, physical activity, drugs and much more. Most studies focused on
      long-term exposure to various factors; however, since bacterial growth is rapid (doubling
      time of S. typhimurium under optimal conditions = 20min), even short-term variations in the
      environment could dramatically influence the human microbiota.

      In the lab of Prof. WD Hardt, a mouse model of S. typhimurium enterocolitis has been
      established. Since most mouse strains are resistant against colonization with S. typhimurium,
      pretreatment with antibiotics is a requirement for induction of S. typhimurium enterolitis.
      However, recent experiments in the Hardt lab revealed, that in mice, 24 h exposure to a
      high-fat diet also results in a breakdown of colonization resistance, leading to Salmonella
      enterocolitis upon S. typhimurium infection. The same is true for E. coli strains. Subsequent
      experiments demonstrated that exposure to fatty acids is sufficient to overcome colonization
      resistance. Mechanistic experiments identified fat-elicited bile-release as the underlying
      mechanism: Exposure to a high fat diet leads to increased bile acid secretion; S. typhimurium
      can tolerate 10-fold higher bile acid concentrations than commensal bacterial, leading to a
      growth advantage of S. typhimurium compared to competing bacteria (WD Hardt et al.,
      unpublished data).

      The aim of this study is to verify the results of this study in human healthy volunteers. The
      nutritional habits of all participants will be carefully evaluated. In the intervention
      phase, participants will be exposed to either high-fat or low-fat diet and a controlled dose
      of the non-pathogenic bacteria E. coli Nissle. E. coli Nissle is the active compound for
      "Mutaflor®" and other probiotics. E. coli Nissle has therapeutic effects for the treatment of
      chronic inflammatory intestinal diseases. In contrast to other non-pathogenic E. coli
      strains, it exhibits a specific pattern of fitness factors but lacks prominent virulence
      factors. In vivo and in vitro experiments demonstrated both, protective effects against
      infection with intestinal pathogens as well as potent immunomodulatory properties. Growth of
      E. coli Nissle in the human gut resembles growth of S. typhimurium. Both bacteriae also share
      metabolic requirements for intestinal growth. Therefore, growth E. coli Nissle in the human
      intestine can be used as a marker for growth of E. coli strains, Salmonella typhimurium and
      related pathogens.

      It is planned to enumerate E. coli Nissle counts in the stool after Mutaflor ingestion and to
      quantify other changes of the human microbiota. The hypothesize is that a high-fat diet,
      leading to increased bile acid secretion results in favorable growth conditions for E. coli
      Nissle, resulting in high bacterial counts in the stool.

      The results of the study will help improving the understanding of the consequences of
      nutritional composition on the vulnerability of the human organism to bacterial infections.
      Such an improved understanding might enable designing preventive measures for the growth of
      unwanted E. coli strains (e.g. ESBL, pathogenic) or S. typhimurium infection and/ or a severe
      disease course and might ultimately help limiting antibiotic use and the evolution of
      antibiotic resistant pathogens.
allocation: Randomized
intervention model: Crossover Assignment
intervention model description: randomized controlled crossover clinical study
primary purpose: Basic Science
masking: Single (Investigator)
masking description: Participants will not be blinded regarding the composition of their nutrition. Investigators performing stool and blood analyses will be blinded to the group assignment of the participants.
measure: Maximum concentration of E. coli Nissle bacteriae in all stool samples of each participant
time frame: 1, 2 and 5 days after E. coli Nissle inoculation
description: Each participant's fecal samples will be analyzed for E. coli Nissle bacteriae. Only the stool samples acquired in intervention phase 1 will be considered. For each participant, the maximum concentration of E. coli Nissle in all stool samples (assessed by qPCR) will be used for the calculation of the primary outcome.
measure: Comparison of E. coli Nissle concentration in feces between high-fat diet and low-fat diet
time frame: 1, 2 and 5 days after E. coli Nissle inoculation
description: The concentration of E. coli Nissle bacteriae (CFU per g feces) in participants exposed to high-fat diet will be compared to the concentration of E. coli Nissle bacteriae in individuals exposed to low-fat diet (Mann-Whitney U test, a p-value <0.05 will be considered significant).
measure: Chemical composition of blood
time frame: Week 1 - 8
description: For each participant's blood samples the chemical composition including bile acids, lipids, cholesterol and other compounds related to fat, cholesterol and bile acid metabolism will be determined (concentration, per μl blood). Samples at baseline, during intervention phase and the washout phase will be analyzed. For each compound the group exposed to low-fat diet and high-fat diet will be compared, respectively (intervention phase) or the group with the lowest and highest fat ingestion according to the nutritional protocol.
measure: Chemical composition of stool
time frame: Week 1 - 8
description: For each participant's stool samples the chemical composition including bile acids, lipids, cholesterol and other compounds related to fat, cholesterol and bile acid metabolism will be determined (concentration, per g stool). Samples at baseline, during intervention phase and the washout phase will be analyzed. For each compound the group exposed to low-fat diet and high-fat diet will be compared, respectively (intervention phase) or the group with the lowest and highest fat ingestion according to the nutritional protocol.
measure: Microbiota composition: taxonomic composition
time frame: Week 1 - 8
description: Same as 4, only the microbiota taxonomic composition in stool samples will be analyzed by ribosomal RNA gene sequencing. Analysis will also include tests for microbiota diversity (i.e. number of bacteria species identified). Findings will be compared to changes occurring in the microbiota of participants in the other study group.
measure: Microbiota composition: metagenomic properties
time frame: Week 1 - 8
description: Same as 4, only the metagenomic properties of the microbiota in stool samples will be analyzed by whole genome shotgun sequencing. Analyses will also test for metabolic pathways used by the microbiota. Microbiological and molecular biology methods will also be used to characterize bacteria strains associated with high-fat diet, low-fat diet and/ or changes in bile acid concentration.
measure: Microbiota composition: E. coli content
time frame: Week 1 - 8
description: Same as 4, only the E. coli content of stool samples will be analyzed by sequencing and conventional plating techniques. This will quantify E. coli Nissle and also all endogenous E. coli strains present in the sample.
measure: Antibody response against E. coli Nissle
time frame: 3 weeks after inoculation of E. coli Nissle
description: Antibody titers against E. coli Nissle will be determined by bacterial FACS or other appropriate techniques. Antibody titers at baseline, at 2 weeks and at 3 weeks will be determined. Individuals exposed to low-fat diet and high-fat diet will be compared. Measured variable: Antibody titers against E. coli Nissle and various E. coli strains.
arm group label: High-fat diet
arm group type: Active Comparator
description: Participants will follow a high-fat diet. During the intervention phase, they will inoculate "Mutaflor Suspension" (E. coli Nissle 1917) (Single dose, 5 ml = 5x10^8 CFU).
Blood samples, stool samples and clinical information will be collected during the study.
arm group label: Low-fat diet
arm group type: Active Comparator
description: Participants will follow a low-fat diet. During the intervention phase, they will inoculate "Mutaflor Suspension" (E. coli Nissle 1917) (Single dose, 5 ml = 5x10^8 CFU).
Blood samples, stool samples and clinical information will be collected during the study.
intervention type: Drug
intervention name: "Mutaflor Suspension" (E. coli Nissle 1917)
description: Inoculation of "Mutaflor Suspension" (E. coli Nissle 1917)
arm group label: High-fat diet
arm group label: Low-fat diet
other name: Mutaflor Suspension
intervention type: Other
intervention name: Blood samples
description: Blood samples will be collected and analyzed at different study time points
arm group label: High-fat diet
arm group label: Low-fat diet
intervention type: Other
intervention name: Stool samples
description: Stool samples will be collected and analyzed at different study time points
arm group label: High-fat diet
arm group label: Low-fat diet
intervention type: Other
intervention name: Clinical information
description: Clinical information will be collected at different study time points using questionnaires
arm group label: High-fat diet
arm group label: Low-fat diet
criteria: 
gender: All
minimum age: 18 Years
maximum age: 85 Years
healthy volunteers: Accepts Healthy Volunteers
last name: Wolf-Dietrich Hardt, Prof. Dr.
role: Principal Investigator
affiliation: ETH Zurich, Institute of Microbiology
last name: Benjamin Misselwitz, MD
phone: +41 44 255 1111
email: benjamin.misselwitz@usz.ch
last name: Wolf-Dietrich Hardt, Prof. Dr.
phone: +41 44 632 51 43
email: hardt@micro.biol.ethz.ch
facility: 
contact: 
country: Switzerland
responsible party type: Sponsor
mesh term: Escherichia coli Infections