The Symbiont-Restore Study

NCT05942586 | Completed

• 1 other identifier: APC165
• Study Type: interventional
• Target: 137
• Locations: 1 country
• Sites: 1

Brief Summary

Within the framework of the Science Foundation Ireland funded Microbe Restore Project, the Symbiont Restore Study is an Investigator-initiated trial which explores the prospective health advantages associated with a particular bacterium known as Limosilactobacillus reuteri (L. reuteri) PB-W1™. In the Symbiont Restore Study, we seek to determine if supplementation with L. reuteri PB-W1™, can beneficially alter the composition and function of the gut microbiome, particularly in terms of immunomodulatory benefits, intestinal health, satiety, as well as markers of psychological stress and sleep quality. Additionally, this study will explore whether combining this strain with a prebiotic blend of dietary fibres (comprising 50 % raffinose and 50 % xylooligosaccharide) through a "synbiotic" approach can enhance its therapeutic benefits.

Conditions

Obesity

Keywords

Gut Microbiome; Microbiota; Bacterial Physiological Phenomena; Papua New Guinea; Limosilactobacillus reuteri; Probiotics; Prebiotics; Immunomodulation; Synbiotics; Immune System; Metabolome; Gastrointestinal microbiome; Satiation; Hunger; Dietary fibre; Raffinose; Microbial ecology; Randomised Controlled Trial

Outcome Measures

Primary Outcomes (1)

• Change from Baseline Immune Profile at 8 Weeks

  Change from baseline serum cytokine concentrations measured using established methods and immune cell response determined through stimulation assays on peripheral blood mononuclear cells at 8 weeks.

  The assessments will be conducted at baseline (pre-intervention) and at the end of the eight-week intervention period.

Secondary Outcomes (4)

• Change from Baseline Faecal Microbiome Composition and Diversity at 8 Weeks

  The assessments will be conducted at baseline (pre-intervention) and at the end of the eight-week intervention period.

• Change from Baseline Metabolic Profile at 8 Weeks

  The assessments will be conducted at baseline (pre-intervention) and at the end of the eight-week intervention period.

• Change from Baseline Satiety Rating over 8 Week Intervention

  Throughout the eight-week intervention period, assessed at specific time points (i.e., weekly) during the study.

• Gastrointestinal Tolerance to Dietary Fibre

  Throughout the eight-week intervention period, assessed at specific time points (i.e., weekly) during the study.

Other Outcomes (2)

• Change from Baseline Perceived Stress at 8 Weeks

  The assessments will be conducted at baseline (pre-intervention) and at the end of the eight-week intervention period.

• Change from Baseline Sleep Quality at 8 Weeks

  The assessments will be conducted at baseline (pre-intervention) and at the end of the eight-week intervention period.

Study Arms (4)

Probiotic Arm

ACTIVE COMPARATOR

30 Participants in this arm will undergo a two-week run-in period consuming placebo sachet (maltodextrin) for the first week and then increasing the dosage in the second week. Following the run-in period, Participants will receive an eight-week intervention consisting of daily consumption of placebo sachets and probiotic capsule containing L. reuteri PB-W1™.

Dietary Supplement: Probiotic capsule (L. reuteri PB-W1™), Placebo sachet

Prebiotic Arm

ACTIVE COMPARATOR

30 Participants in this arm will undergo a two-week run-in period consuming prebiotic sachets (Prebiotic Blend) for the first week and then increasing the dosage in the second week. During the eight-week intervention, Participants will consume prebiotic sachets three times daily and placebo capsule.

Dietary Supplement: Prebiotic sachet (Prebiotic Blend), Placebo capsule

Synbiotic Arm

EXPERIMENTAL

30 Participants in this arm will undergo a two-week run-in period consuming prebiotic sachets (Prebiotic Blend) for the first week and then increasing the dosage in the second week. Following the run-in period, Participants will receive an eight-week intervention consisting of daily consumption of prebiotic sachets, probiotic capsule containing L. reuteri PB-W1™.

Combination Product: Probiotic capsule (L. reuteri PB-W1™), Prebiotic sachet (Prebiotic Blend)

Placebo Arm

PLACEBO COMPARATOR

30 Participants in this arm will undergo a two-week run-in period consuming placebo sachet (maltodextrin) for the first week and then increasing the dosage in the second week. During the eight-week intervention, Participants will consume placebo sachets three times daily and placebo capsule.

Dietary Supplement: Placebo sachet, Placebo capsule

Interventions

Probiotic capsule (L. reuteri PB-W1™), Placebo sachet DIETARY_SUPPLEMENT

Participants in this arm will consume one probiotic capsule (L. reuteri PB-W1™) daily and placebo sachets three times daily (morning, midday, and evening) for a total daily dose of 7.5 g throughout the eight-week intervention period.

Probiotic Arm

Prebiotic sachet (Prebiotic Blend), Placebo capsule DIETARY_SUPPLEMENT

Participants in this arm will consume one placebo capsule daily and prebiotic sachets (Prebiotic Blend) three times daily (morning, midday, and evening) for a total daily dose of 15 g throughout the eight-week intervention period.

Prebiotic Arm

Probiotic capsule (L. reuteri PB-W1™), Prebiotic sachet (Prebiotic Blend) COMBINATION_PRODUCT

Participants in this arm will consume one probiotic capsule (L. reuteri PB-W1™) daily and prebiotic sachets (Prebiotic Blend) three times daily (morning, midday, and evening) for a total daily dose of 15 g throughout the eight-week intervention period.

Synbiotic Arm

Placebo sachet, Placebo capsule DIETARY_SUPPLEMENT

Participants in this arm will consume one placebo capsule daily and placebo sachets three times daily (morning, midday, and evening) for a total daily dose of 7.5 g throughout the eight-week intervention period.

Placebo Arm

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• To be considered eligible for enrolment into the study, potential Participants must:
• Be able to give written informed consent.
• Be between 18 and 55 years of age.
• Self-identify as White.
• Have a BMI of 30-40 kg/m2 and waist circumference of ≥102cm (males) or ≥88cm (females).
• Have a stable body weight (≤5% change) over the past three months.
• Be in general good health, as determined by interview and having systolic blood pressure less than 160 mm Hg and diastolic blood pressure less than 100 mm Hg (defined as hypertension stage 2), taken by the investigator.
• Be willing to avoid consuming dietary supplements, prebiotics, probiotics, or fibre-rich supplements within four weeks prior to the baseline visit and until the end of the study.
• Be willing to maintain their current level of physical activity.
• Be willing to consume the investigational product daily for the duration of the study.
• Be willing to maintain their habitual diet for the duration of the study.

You may not qualify if:

• Potential Participants will be excluded from the study if they meet any of the below criteria:
• Are pregnant, lactating or post-menopausal or women who are planning to become pregnant over the study period.
• Have hypersensitivity, allergy, or intolerance to any of the components of the investigational products.
• Have received antibiotic treatment within three months prior to baseline.
• Are taking a medication that the investigator believes would interfere with the objectives of the study, pose a safety risk, or confound the interpretation of the study results. Participants should have a wash-out period of two-weeks for each of these medications except for antibiotics, which should not have been taken in the previous three months. Participants taking proton pump inhibitors will be allowed into the study if the dose has been stable for at least two months prior to baseline. Similarly, occasional use of over-the-counter non-steroidal analgesics may be acceptable (at the discretion of the Chief Investigator). However, participants will be required to note any medications consumed via the Medical History, Medications and Supplements Log (MR2006).
• Have a history or indication of drug and/or alcohol abuse at the time of enrolment.
• Have a significant active and medically diagnosed acute or chronic co-existing illness including metabolic, psychiatric, or gastrointestinal disease (such as diarrhoea, Crohn's disease, ulcerative colitis, IBS, diverticulosis, stomach or duodenal ulcers, hepatitis A/B/C, HIV, cancer etc.). Participants that have a significant family history of such diseases or any other condition which contraindicates, in the investigator's judgement, entry to the study will also be excluded.
• Habitual consumption of \>2 alcoholic beverages/day (\>28g ethanol/day).
• Are vegetarian or vegan, those with a typical fibre intake of \>30g/day and those that have used dietary supplements (prebiotics/probiotics) in the month leading up to the study.
• Have made major dietary changes within three months prior to baseline and those with major lifestyle changes planned during the study (e.g., diet, exercise, extensive travel etc).
• Those with clinically diagnosed eating disorders.
• Have active gastrointestinal disorder or previous gastrointestinal surgery.
• Have a chronic medication treatment (e.g., anti-hypertensive medications) of unstable dosage, defined as having been changed within two months prior to baseline.
• Are severely immunocompromised (HIV positive, transplant recipients, on any anti-rejection medications, on a systemic-acting steroid for \>30 days, or have had chemotherapy or radiotherapy in the last 12 months.
• Have a malignant disease or any concomitant end-stage organ disease.

Sponsors & Collaborators

• University College Cork: lead
• Novozymes A/S: collaborator

Study Sites (1)

University College Cork

Cork, Cork, Ireland

Location

Related Publications (6)

• Martinez I, Stegen JC, Maldonado-Gomez MX, Eren AM, Siba PM, Greenhill AR, Walter J. The gut microbiota of rural papua new guineans: composition, diversity patterns, and ecological processes. Cell Rep. 2015 Apr 28;11(4):527-38. doi: 10.1016/j.celrep.2015.03.049. Epub 2015 Apr 16.

  PMID: 25892234 BACKGROUND

• Walter J, Britton RA, Roos S. Host-microbial symbiosis in the vertebrate gastrointestinal tract and the Lactobacillus reuteri paradigm. Proc Natl Acad Sci U S A. 2011 Mar 15;108 Suppl 1(Suppl 1):4645-52. doi: 10.1073/pnas.1000099107. Epub 2010 Jun 25.

  PMID: 20615995 BACKGROUND

• Lorea Baroja M, Kirjavainen PV, Hekmat S, Reid G. Anti-inflammatory effects of probiotic yogurt in inflammatory bowel disease patients. Clin Exp Immunol. 2007 Sep;149(3):470-9. doi: 10.1111/j.1365-2249.2007.03434.x. Epub 2007 Jun 22.

  PMID: 17590176 BACKGROUND

• Cervantes-Barragan L, Chai JN, Tianero MD, Di Luccia B, Ahern PP, Merriman J, Cortez VS, Caparon MG, Donia MS, Gilfillan S, Cella M, Gordon JI, Hsieh CS, Colonna M. Lactobacillus reuteri induces gut intraepithelial CD4+CD8alphaalpha+ T cells. Science. 2017 Aug 25;357(6353):806-810. doi: 10.1126/science.aah5825. Epub 2017 Aug 3.

  PMID: 28775213 BACKGROUND

• Zelante T, Iannitti RG, Cunha C, De Luca A, Giovannini G, Pieraccini G, Zecchi R, D'Angelo C, Massi-Benedetti C, Fallarino F, Carvalho A, Puccetti P, Romani L. Tryptophan catabolites from microbiota engage aryl hydrocarbon receptor and balance mucosal reactivity via interleukin-22. Immunity. 2013 Aug 22;39(2):372-85. doi: 10.1016/j.immuni.2013.08.003.

  PMID: 23973224 BACKGROUND

• Roager HM, Licht TR. Microbial tryptophan catabolites in health and disease. Nat Commun. 2018 Aug 17;9(1):3294. doi: 10.1038/s41467-018-05470-4.

  PMID: 30120222 BACKGROUND

MeSH Terms

Conditions

Obesity

Interventions

Probiotics

Condition Hierarchy (Ancestors)

Overweight; Overnutrition; Nutrition Disorders; Nutritional and Metabolic Diseases; Body Weight; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Dietary Supplements; Food; Diet, Food, and Nutrition; Physiological Phenomena; Food and Beverages

Study Officials

• Jens Walter

  University College Cork

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: FACTORIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: This trial will be conducted as a single-blinded, 2 × 2 factorial design intervention study to systematically compare the effects of the probiotic (L. reuteri PB-W1™), the prebiotic blend (comprising 50 % raffinose and 50 % xylooligosaccharide), the synbiotic (a combination of the probiotic and the prebiotic blend) and relevant placebo controls (maltodextrin in place of the prebiotic blend and placebo capsules in place of the probiotic)

Study Record Dates

• First Submitted: June 2, 2023
• First Posted: July 12, 2023
• Study Start: May 22, 2023
• Primary Completion: December 4, 2024
• Study Completion: December 4, 2024
• Last Updated: February 10, 2025

Record last verified: 2024-12

Data Sharing

• IPD Sharing: Will not share

Locations

IE (1)