Effects of β-glucans on Gut Permeability and Microbiota in Elderly

Effects of β-glucan Based Dietary Fibres on Indomethacin-induced Hyperpermeability and Gut Microbiota Composition in Elderly: A Randomized Placebo-controlled Crossover Clinical Trial

The investigators aim was to compare healthy young adults, senior orienteers (model of healthy ageing) and elderly with gastrointestinal symptoms on intestinal permeability, microbiota compositions and well-being. In addition, assess whether 3 weeks of oral intake of soluble or dispersible forms yeast-dervied beta-glucan could improve intestinal barrier function against drug-induced barrier disruption vs placebo for a cohort of elderly people with gastrointestinal symptoms, in a randomized double blinded placebo-controlled cross-over clinical trial.

Study Overview

• Status: Completed
• Conditions: Elderly; Bowel Symptoms; Prebiotics
• Intervention / Treatment: Dietary supplement: yeast-beta glucan

Detailed Description

Baseline samples for measurements of intestinal permeability (multisugar test), microbiota composition (faecal samples) and well-being (questionnaires) were collected during the first week for:

Young healthy adults (healthy young controls) Senior orienteers (healthy elderly controls) Elderly with gastrointestinal (GI) symptoms

Thereafter only the elderly with GI symptoms continued into the randomized cross-over trial where they were blindly and randomly distributed one of the following: Soluble yeast-derived beta-glucan, dispersible (whole) yeast-derived beta-glucan and placebo. Each supplement was taken for 3 weeks with a 1 week washout until all participants had taken all supplements. Towards the end of each supplement period, samples for measurement of intestinal permeability and microbiota were collected, in addition to questionnaires being filled out.

• Study Type: Interventional
• Enrollment (Actual): 43
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Sweden
  • Örebro, Sweden, 70362
    • Campus USÖ, Örebro University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 55 years to 100 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Elderly with gastrointestinal symptoms

Inclusion Criteria:

• Informed consent signed by study participant
• Age >55 years
• Scoring above 2 on the dimensions for diarrhoea and constipation on the Gastrointestinal symptoms rating scale (GSRS)
• Mentally and physically fit to complete questionnaires during the study period

Exclusion Criteria:

• Known or genic gastrointestinal diseasewith strictures, malignance's and ischemia.
• Inflammatory bowel diseases (IBD)
• Participation in other clinical trials in the past three months.
• Intake of medications know to change the inflammatory status (i.e proton pump inhibitors, antibiotic, anti-inflammtory medication (including NSAIDs)

Healthy controls

Inclusion Criteria:

• Age ≥ 18 years
• Informed consent signed by the study participant
• Mentally and physically fit to complete questionnaires during the study period

Exclusion Criteria:

• Previous abdominal surgery
• A hypertonic condition demanding medical treatment
• Diagnosed psychiatric disease
• Lactose intolerance
• Usage of medical prescribed medications, expect oral contraceptives, during the 14 days preceding study start
• Premenstrual syndrome
• Pregnant or breast feeding
• Known or genic gastrointestinal disease, with strictures, malignance's and ischemia.
• Inflammatory bowel diseases (IBD)
• Participation in other clinical trials in the past three months.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Triple

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Elderly with gastrointestinal symptoms; The target group for the intervention and cohort of interest used for comparison of baseline characteristics between control groups. Went into a cross-over design with 2 yeast-derived beta-glucan supplements and a placebo.	Dietary supplement: yeast-beta glucan
No Intervention: Senior orienteers; A model of healthy aged elderly used as a control group for the baseline characteristics.
No Intervention: Young healthy adults; A cohort of young healthy adults used as a control group for the baseline characteristics.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Intestinal permeability at baseline (before indomethacin)	In vivo gastrointestinal permeability measured by oral intake of multi-sugar test before intake of indomethacin. Urine collected over 24 hours for measurement of excreted sugars.	Day 1
Intestinal permeability at baseline (after indomethacin)	In vivo gastrointestinal (GI) permeability measured by oral intake of multi-sugar test after intake of indomethacin (GI barrier disruption challenge). Urine collected over 24 hours for measurement of excreted sugars.	Day 1
Changes in Intestinal permeability 3 weeks after study supplementation 1 (before indomethacin).	Performed after study participants have orally taken study supplementation 1 for 3 weeks. In vivo gastrointestinal permeability measured by oral intake of multi-sugar test before intake of indomethacin. Urine collected over 24 hours for measurement of excreted sugars.	3 weeks
Changes in intestinal permeability 3 weeks after study supplementation 1 (after indomethacin).	Performed after study participants have orally taken study supplementation 1 for 3 weeks. In vivo gastrointestinal (GI) permeability measured by oral intake of multi-sugar test after intake of indomethacin (GI barrier disruption challenge). Urine collected over 24 hours for measurement of excreted sugars.	3 weeks
Changes in intestinal permeability 3 weeks after study supplementation 2 (before indomethacin)	Performed after study participants have orally taken study supplementation 2 for 3 weeks. In vivo gastrointestinal permeability measured by oral intake of multi-sugar test before intake of indomethacin. Urine collected over 24 hours for measurement of excreted sugars.	3 weeks
Changes in intestinal permeability 3 weeks after study supplementation 2 (after indomethacin)	Performed after study participants have orally taken study supplementation 2 for 3 weeks. In vivo gastrointestinal (GI) permeability measured by oral intake of multi-sugar test after intake of indomethacin (GI barrier disruption challenge). Urine collected over 24 hours for measurement of excreted sugars.	3 weeks
Changes in intestinal permeability 3 weeks after study supplementation 3 (before indomethacin)	Performed after study participants have orally taken study supplementation 3 for 3 weeks. In vivo gastrointestinal permeability measured by oral intake of multi-sugar test before intake of indomethacin. Urine collected over 24 hours for measurement of excreted sugars.	3 weeks
Changes in intestinal permeability 3 weeks after study supplementation 3 (after indomethacin)	Performed after study participants have orally taken study supplementation 3 for 3 weeks. In vivo gastrointestinal (GI) permeability measured by oral intake of multi-sugar test after intake of indomethacin (GI barrier disruption challenge). Urine collected over 24 hours for measurement of excreted sugars.	3 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Microbiota diversity - at baseline	Faecal samples will be used for next-generation sequencing and analysed for diversity	Day 1
Bacterial species - at baseline	Faecal samples will be used for next-generation sequencing and analysed for bacterial species	Day 1
Changes in microbiota diversity 3 weeks after study supplementation 1	Faecal samples will be used for next-generation sequencing and analysed for changes in microbiota diversity	3 weeks
Changes in bacterial species 3 weeks after study supplementation 1	Faecal samples will be used for next-generation sequencing and analysed for changes in bacterial species levels	3 weeks
Changes in microbiota diversity 3 weeks after study supplementation 2	Faecal samples will be used for next-generation sequencing and analysed for changes in microbiota diversity	3 weeks
Changes in bacterial species 3 weeks after study supplementation 2	Faecal samples will be used for next-generation sequencing and analysed for changes in bacterial species levels	3 weeks
Changes in microbiota diversity 3 weeks after study supplementation 3	Faecal samples will be used for next-generation sequencing and analysed for changes in microbiota diversity	3 weeks
Changes in bacterial species 3 weeks after study supplementation 3	Faecal samples will be used for next-generation sequencing and analysed for changes in bacterial species levels	3 weeks
Changes in microbiota diversity - Washout (1 week after ending supplementation 1, i.e. 4 weeks after baseline)	Faecal samples will be used for next-generation sequencing and analysed for changes in microbiota diversity from 1 weeks washout, after ending study supplementation 1 (4 weeks after baseline)	4 weeks
Changes in bacterial species - Washout (1 week after ending study supplementation 1, i.e. 4 weeks after baseline)	Faecal samples will be used for next-generation sequencing and analysed for changes in bacterial species from 1 weeks washout, after ending study supplementation 1 (4 weeks after baseline)	4 weeks
Changes in microbiota diversity - Washout (1 week after ending study supplementation 2, i.e. 4 weeks after baseline)	Faecal samples will be used for next-generation sequencing and analysed for changes in microbiota diversity from 1 weeks washout, after ending study supplementation 2 (4 weeks after baseline)	4 weeks
Changes in bacterial species - Washout (1 week after ending study supplementation 2, i.e. 4 weeks after baseline)	Faecal samples will be used for next-generation sequencing and analysed for changes in bacterial species from 1 weeks washout, after ending study supplementation 2 (4 weeks after baseline).	4 weeks
Changes in microbiota diversity - Washout (1 week after ending study supplementation 3, i.e. 4 weeks after baseline)	Faecal samples will be used for next-generation sequencing and analysed for changes in microbiota diversity from 1 weeks washout, after ending study supplementation 3 (4 weeks after baseline)	4 weeks
Changes in bacterial species - Washout (1 week after ending study supplementation 3, i.e. 4 weeks after baseline)	Faecal samples will be used for next-generation sequencing and analysed for changes in bacterial species from 1 weeks washout, after ending study supplementation 3 (4 weeks after baseline)	4 weeks
Changes in gastrointestinal symptom questionnaire scores	The Gastrointestinal Symptoms Rating Scale (GSRS) evaluates gastrointestinal (GI) symptoms based on the 5 domains diarrhoea, constipation, reflux, indigestion and abdominal pain. The symptoms are assessed with 15 items, ranging in scores 1 to 7 depending on their severity. A score of 1 represents "no problems" and score 7 represents "severe problems". The severity of symptoms may be defined as no problems (1 point), mild (1-2 points), moderate (2-4 points), and severe (4-7 points). The scores for each domain was calculated as the mean score of each corresponding item while the mean total GSRS score reflects the general severity of GI symptoms.	up to 13 weeks
Changes in hospital and anxiety depression scores	The Hospital Anxiety and Depression Scale (HADS) was used to evaluate the psychological distress of study participants.This questionnaire consists of 14 items subdivided in two subscales for the assessment of anxiety or depression. The total score is used as a measure of general psychological distress. The minimum score is 0 and the maximum score is 21. A score > 8 on respective subscales indicates a significant level of anxiety or depression.	up to 13 weeks
Changes in perceived stress scale scores	The perceived stress scale (PSS) consists of 10 items, including a number of direct questions about current levels of experienced stress. The respondent answers how often a certain emotion has been present during the past month. PSS scores are obtained by reversing responses (e.g., 0 = 4, 1 = 3, 2 = 2, 3 = 1 & 4 = 0) to the four positively stated items (items 4, 5, 7, & 8) and then summing across all scale items. Each item is rated on a 5-point scale ranging from never (0) to almost always (4). The questions in this scale ask about the responders feelings and thoughts during the last month. In each case the questionnaire requires the respondent to indicate by circling how often they felt or thought a certain way.	Up to 13 weeks
Changes in quality of life questionnaire scores	The EuroQol 5D-5L (EQ-5D-5L) tool consists of two parts; 5Q-5D, which includes 5 items related to wellbeing and function (mobility, self-care, usual activities, pain/discomfort and anxiety/ depression) and the visual analogue scale, 5Q-5D-VAS, ranging from 0 to 100.	Up to 13 weeks

Collaborators and Investigators

• Sponsor: Örebro University, Sweden
• Collaborators: Kerry Group
• Investigators: Principal Investigator: Robert J Brummer, PhD/MD, Örebro University, Sweden

Study record dates

Study Major Dates

• Study Start (Actual): April 1, 2015
• Primary Completion (Actual): August 14, 2017
• Study Completion (Actual): August 14, 2017

Study Registration Dates

• First Submitted: October 3, 2022
• First Submitted That Met QC Criteria: October 13, 2022
• First Posted (Actual): October 18, 2022

Study Record Updates

• Last Update Posted (Actual): March 23, 2023
• Last Update Submitted That Met QC Criteria: March 21, 2023
• Last Verified: March 1, 2023

More Information

Terms related to this study

• Keywords: Microbiota; elderly; clinical trial; Health; prebiotics; permeability
• Other Study ID Numbers: FODI

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No