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Rewilding the Human Gut: Reintroduction of the Species Lactobacillus Reuteri

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03501082
Recruitment Status : Completed
First Posted : April 18, 2018
Last Update Posted : May 5, 2020
Sponsor:
Information provided by (Responsible Party):
University of Alberta

Brief Summary:

Our guts are home to millions of microbes. These microbes help our bodies do important tasks like digesting food, fighting diseases and making vitamins. The type of microbes present in our gut depends on factors like diet, the use of medications, and sanitation practices. Research shows the diversity of the microbes living in our gut is decreasing, especially as countries become more developed. For example, stool samples from rural Papua New Guineans contain an additional 50 species not found in people living in the United States.

What has caused the disappearance of L. retueri is currently unknown. However, it is known that in order to help this species to grow specific types of carbohydrates need to be consumed. People in North America eat much less of these carbohydrates compared to rural Papua New Guineas. Examples of foods containing these carbohydrates include yams, beans, and artichokes. It may be possible for L. reuteri to live in the human gut if it is taken as a probiotic and a diet containing the types of foods which helps it grow is eaten. Furthermore, if L. reuteri can be re-established, it may have beneficial effects on how our immune system works.

The investigators hypothesize that L. Reuteri can be re-established in the gut of Canadians when they are fed a diet containing the types of foods known to help it grow. To test this hypothesize, the survival of two strains of L. Reuteri in the gut of Canadians will be compared when they eat their usual diet, to when they eat a diet containing the types of food known to help L. Reuteri survive. We will measure the amount of L. retueri present in stool samples of participants, and measure changes in metabolic and immune markers that occur as a result of the intervention. This study will help determine if a 'lost' species can be reintroduced into the human gut, and if this is associated with immune and metabolic health.


Condition or disease Intervention/treatment Phase
Microbial Colonization Other: L Reuteri PB-W1 Strain Other: L. Reuteri DSM20016T Strain Other: Placebo Not Applicable

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 30 participants
Allocation: Randomized
Intervention Model: Crossover Assignment
Intervention Model Description: Randomized three arm cross over placebo controlled trial
Masking: Double (Participant, Investigator)
Primary Purpose: Other
Official Title: Rewilding the Human Gut: Reintroduction of the Species Lactobacillus Reuteri
Actual Study Start Date : February 21, 2019
Actual Primary Completion Date : January 31, 2020
Actual Study Completion Date : January 31, 2020

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: L. Reuteri PB-W1 Western Diet Start
5 participants will be assigned to this group and provided with a one time dose of L. Reuteri PB-W1 strain provided on day 4 of each diet period. 5 of the participants will be assigned to consume their usual diet for the first diet period. The L. Reuteri PB-W1 strain will be provided as a drinkable solution (approximately 2.25x10^10 viable cells will be provided in 50 ml of water).
Other: L Reuteri PB-W1 Strain
L. Reuteri PB-W1 strain will be prepared in accordance to the standardized operating procedures to prepare Lactobacillus reuteri in food grade conditions
Other Name: Probiotic

Experimental: L. Reuteri DSM20016T Western Diet Start
5 participants will be assigned to this group and provided with a one time dose of L. Reuteri DSM20016T strain provided on day 4 of each diet period. 5 of the participants will be assigned to consume their usual diet for the first diet period. The L. Reuteri DSM20016T strain will be provided as a drinkable solution (approximately 2.25x10^10 viable cells will be provided in 50 ml of water).
Other: L. Reuteri DSM20016T Strain
L. Reuteri DSM20016T strain will be prepared in accordance to the standardized operating procedures to prepare Lactobacillus reuteri in food grade conditions
Other Name: Probiotic

Placebo Comparator: Placebo Western Diet Start
5 participants will be assigned to this group and provided with a one time dose of a placebo provided on day 4 of each diet period. 5 of the participants will be assigned to consume their usual diet for the first diet period. The placebo will be provided as a drinkable solution (approximately 2 g maltodextrain dissolved in 50 ml of water).
Other: Placebo
2 g of maltodextrin will be dissolved in 50 ml water in food grade conditions

Experimental: L. Reuteri PB-W1 Non-Western Diet Start
5 participants will be assigned to this group and provided with a one time dose of L. Reuteri PB-W1 strain provided on day 4 of each diet period.The participants will be assigned to consume a non-western diet that will be prepared by the research team. The L. Reuteri PB-W1 strain will be provided as a drinkable solution (approximately 2.25x10^10 viable cells will be provided in 50 ml of water).
Other: L Reuteri PB-W1 Strain
L. Reuteri PB-W1 strain will be prepared in accordance to the standardized operating procedures to prepare Lactobacillus reuteri in food grade conditions
Other Name: Probiotic

Experimental: L. Reuteri DSM20016T Non-West Diet Start
5 participants will be assigned to this group and provided with a one time dose of L. Reuteri DSM20016T strain provided on day 4 of each diet period. The participants will be assigned to consume a non-western diet that will be prepared by the research team. The L. Reuteri DSM20016T strain will be provided as a drinkable solution (approximately 2.25x10^10 viable cells will be provided in 50 ml of water).
Other: L. Reuteri DSM20016T Strain
L. Reuteri DSM20016T strain will be prepared in accordance to the standardized operating procedures to prepare Lactobacillus reuteri in food grade conditions
Other Name: Probiotic

Placebo Comparator: Placebo Non-Western Diet Start
5 participants will be assigned to this group and provided with a one time dose of a placebo provided on day 4 of each diet period. The participants will be assigned to consume a non-western diet that will be prepared by the research team. The placebo will be provided as a drinkable solution (approximately 2 g maltodextrain dissolved in 50 ml of water).
Other: Placebo
2 g of maltodextrin will be dissolved in 50 ml water in food grade conditions




Primary Outcome Measures :
  1. Establishment of L. Reuteri (PB-W1 & DSM20016T strains) in the gut of Canadian individuals [ Time Frame: 8 days ]
    The primary outcome of this study is to determine if L. Reuteri PB-W1 strain can be established in the gut of Canadian individuals. This will be measured in stool samples by qPCR and culturing methods.

  2. Colonization of L. Reuteri (PB-W1 & DSM20016T strains) pending consumption of diet designed to provide growth substrates for L. Reuteri [ Time Frame: 21 days ]
    We aim to determine if the survival of L. Reuteri in the gut of Canadian individuals is improved by feeding a diet specifically designed to provide growth substrates for L. Reuteri. This will be measured in stool samples by qPCR and culturing methods


Secondary Outcome Measures :
  1. Fecal microbiotia composition changes following provision of L. reuteri strains. [ Time Frame: 8-21 days ]
    16SrRNA-sequencing and whole metagenome sequencing will performed to determine gut microbial community changes following provision of L. Reuteri.

  2. Fecal microbiota composition changes following the provision of a diet designed to promote survival of L. Reuteri strains. [ Time Frame: 8-21 Days ]
    16SrRNA-sequencing and whole metagenome sequencing will performed to determine gut microbial community changes following provision of a diet designed to promote the growth of L. Reuteri.

  3. Impact of L. reuteri strains on host immune response. [ Time Frame: 8 & 21 Days ]
    Host immune response will be measured in blood samples by quantifying IgA, selected cytokines, TNF-alpha, INF- gamma, regulatory T cells, and white blood cell phenotyping using flow cytometry. We also will measure IgA in fecal samples using an ELISA kit.

  4. To characterize changes to the metabolome following provision of L. Reuteri strains. [ Time Frame: 8 & 21 Days ]
    Plasma metabolome L. Reuteri strain associated changes will be measured, specifically, molecules with known immunological functions such as short chain fatty acids and indole derivatives of tryptophan, and bile acids following the provision of the treatment. This will be measured via high performance chemical isotope labeling liquid chromatography mass spectrometry platform.

  5. To characterize changes to the lipidome following provision of L. Reuteri strains. [ Time Frame: 8 & 21 Days ]
    Plasma lipidome L. Reuteri strain associated changes will be measuredl, specifically, molecules with known immunological functions such as short chain fatty acids. These will be measured via ultra-high pressure liquid chromatography quadrupole time of flight mass spectrometry.

  6. L. Reuteri strain associated changes in blood cholesterol. [ Time Frame: 8 & 21 Days ]
    L. Reuteri strain specific changes in cholesterol (triglycerides, low density lipoprotein, high density lipoprotein), and C-reactive protein will be measured in blood samples.

  7. L. Reuteri strain associated changes in insulin and fasting blood glucose. [ Time Frame: 8 & 21 Days ]
    L. Reuteri strain specific changes in insulin and fasting blood glucose will be measured in blood samples.

  8. L. Reuteri strain associated changes in mood state [ Time Frame: 21 days ]
    L. reuteri strain specific changes in individual mood state as measured by the profile of mood states questionnaire.

  9. L Reuteri strain associated immune response to inflammation (ex vivo) [ Time Frame: Day 8 & 21 ]
    Mononuclear cells will be isolated from whole blood on ficoll gradients and the ability of cells to respond to a bacterial challenge (L. reuteri and lipoplysaccharaide) will be determined ex vivo.



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 45 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • Healthy and overweight individuals with a BMI between 20-29.9 kg/m²
  • Preferably have one bowel movement per day
  • Willing to consume prepared study foods (breakfast, lunch dinner, snacks) for a period of 3 weeks
  • Men and pre-menopausal, non-pregnant or non-lactating women
  • Non-vegetarian, non-smoking, and alcohol intake ≤8 drinks/week, and willing to consume 8 drinks per week or less during the course of the study.
  • If consuming probiotic containing foods, willing to discontinue eating same, and substitute with non-probiotic containing foods

    -≤5 h/week of moderate-vigorous exercise.

  • Quantity of L. reuteri in screening fecal sample below 10^4 CFU/g

Exclusion Criteria:

  • History of diabetes, acute or chronic GI illnesses, conditions, or history of GI surgical intervention
  • antibiotic treatment in the last 3 months
  • use of dietary supplements (including prebiotics and probiotics, fiber supplements/bars, digestive enzymes/beano)- if consumed, willing to undergo 4 week pre-intervention washout period, and remain free of supplements for duration of study. Exception: multivitamin or vitamin d supplement (1 week washout period)
  • use of antihypertensive, lipid-lowering, anti-diabetic, anti-inflammatory (i.e corticosteroids or chronic NSAID use), or laxative medications
  • known food allergies or intolerances (including dairy allergic or lactose intolerant)

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03501082


Locations
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Canada, Alberta
University of Alberta
Edmonton, Alberta, Canada, T6G 2E1
Sponsors and Collaborators
University of Alberta
Investigators
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Principal Investigator: Jens Walter, PhD University of Alberta
Principal Investigator: Andrea Haqq, MD University of Alberta
Publications:

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Responsible Party: University of Alberta
ClinicalTrials.gov Identifier: NCT03501082    
Other Study ID Numbers: Pro00077565
First Posted: April 18, 2018    Key Record Dates
Last Update Posted: May 5, 2020
Last Verified: May 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by University of Alberta:
Gut microbiome
Additional relevant MeSH terms:
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Communicable Diseases
Infections
Disease Attributes
Pathologic Processes