Investigating the Possible Link Between Habitual Diet, Physical Activity, Sleeping Patterns, Obesity Status and Age With Gut Bacterial Composition, Gut Barrier Function, Metabolic Endotoxemia, Systemic Inflammation and Glycaemic Control.

In the UK, 25% of the adults are affected by metabolic syndrome (NHS, 2016). Metabolic syndrome is a cluster of different conditions including: hyperglycaemia, insulin resistance hypertriglyceridemia, dyslipidaemia and hypertension. Such individuals also have increased risk of developing type 2 diabetes and cardiovascular disease. The factors contributing to the development of metabolic syndrome are potentially numerous and understudied in humans, with much of what we think we know coming from animal research. Recent animal studies have pointed towards gut health playing a role in metabolic health. More specifically it has been suggested that changes in the composition of the gut microbiota may drive insulin resistance and type 2 diabetes through a mechanism that is linked to increased gut permeability and the development of metabolic endotoxemia and inflammation. Yet, this link has not been confirmed in humans. This research will look at the relationship between diet, physical activity, sleeping patterns, obesity status and age etc. and measures of gut bacterial composition, gut barrier function and metabolic health. Findings will provide us with new insights on the effect of different physiological and behavioural/ lifestyle variables on gut health and metabolic function.

Study Overview

• Status: Unknown
• Conditions: Obesity; Metabolic Syndrome; Insulin Resistance

• Study Type: Observational
• Enrollment (Anticipated): 100

Contacts and Locations

• Study Contact: Name: Malvina Begalli, MSc; Email: M.Begalli@lboro.ac.uk

Study Locations

• United Kingdom
  • Leicestershire
    • Loughborough, Leicestershire, United Kingdom, LE11 3TU
      • Recruiting
      • School of Sport, Exercise and Health Sciences

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

Men and women living in and around Loughborough, Leicestershire, United Kingdom

Description

Inclusion Criteria:

• Men and women aged 18-70 years
• BMI 18.5-50 kg/m2
• Not taking antibiotics and antimicrobial drugs for at least three months
• Both physically active and sedentary individuals will be eligible to take part in the study
• Weight stable (±5kg) for at least 6 months

Excusion Criteria:

• No cardiometabolic (e.g. heart disease, high blood pressure) or inflammatory illness
• Smokers (including the use of vaporisers and e-cigarettes)
• Taking anti-inflammatory drugs (excluding aspirin)

Study Plan

How is the study designed?

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Glycaemic control / Whole body insulin sensitivity index	Assessed by oral glucose tolerance test	Cross-sectional (all outcome measures will be collected within a 4 week period)
Systemic Markers of Metabolic Endotoxemia (for example LBP determined using an ELISA)	Assessed following the collection of fasted blood samples	Cross-sectional (all outcome measures will be collected within a 4 week period)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Gut permeability	Urine samples will be used to assess the ratio of lactulose to mannitol excretion	Cross-sectional (all outcome measures will be collected within a 4 week period)
Anthropometric Measurements (for example height and weight that will be aggregated to report BMI in kg/m^2)	Measured using standard equipment	Cross-sectional (all outcome measures will be collected within a 4 week period)
Fasting Serum Lipid Profile (for example total, HDL and LDL cholesterol, TAG, free fatty acids measured by spectrophotometric assay)	Assessed following the collection of fasted blood samples	Cross-sectional (all outcome measures will be collected within a 4 week period)
Systemic Markers of Inflammation (for example IL-6, CRP determined using an ELISA/ spectrophotometric assay)	Assessed following the collection of fasted blood samples	Cross-sectional (all outcome measures will be collected within a 4 week period)
Systemic Markers of Oxidative Stress (for example protein carbonyls, glutathione and redox enzymes by ELISA/ spectrophotometric assay (in sub-cohort of participants not taking high-dose antioxidant supplements)	Assessed following the collection of fasted blood samples	Cross-sectional (all outcome measures will be collected within a 4 week period)
Fasting hormone concentration (for example ghrelin, leptin measured by ELISA)	Assessed following the collection of fasted blood samples	Cross-sectional (all outcome measures will be collected within a 4 week period)
Characterisation of immune cell migratory capacity using an ex vivo model (in a sub-cohort of obese participants only)	Assessed following the collection of fasted blood samples by flow cytometry analysis	Cross-sectional (all outcome measures will be collected within a 4 week period)
Characterisation of immune cell populations (monocyte subsets) from peripheral blood mononuclear cells	Assessed following the collection of fasted blood samples by flow cytometry analysis	Cross-sectional (all outcome measures will be collected within a 4 week period)
Dietary intake	Assessed via a Food Frequency Questionnaire (FFQ)	Cross-sectional (all outcome measures will be collected within a 4 week period)
Fasting blood pressure	Systolic and diastolic blood pressure and central blood pressure, measured in triplicate using a Mobil-O-Graph following 20 min period of seated rest	Cross-sectional (all outcome measures will be collected within a 4 week period)
Fasting arterial stiffness	Pulse wave analysis and velocity, measured in triplicate using a Mobil-O-Graph following 20 min period of seated rest	Cross-sectional (all outcome measures will be collected within a 4 week period)
Step count	Habitual daily step count as measured by pedometer for 7 consecutive days prior to the first experimental session	Cross-sectional (all outcome measures will be collected within a 4 week period)
Self-reported activity	Participants will complete the International Physical Activity Questionnaire to measure participants' time spent in physical activity.	Cross-sectional (all outcome measures will be collected within a 4 week period)
Sleeping pattern	Habitual sleep pattern will be assessed by sleep diary 7 consecutive days prior to the first experimental session	Cross-sectional (all outcome measures will be collected within a 4 week period)
Functional tests	To be assessed by handgrip strength (measured in force) and timed sit-to-stand movements (measured as time in seconds to perform 5 sit-to-stand movements followed by the maximum number of movements that can be completed in 60 seconds)	Cross-sectional (all outcome measures will be collected within a 4 week period)
Questionnaires	Morningness and Eveningness questionnaire; Mood state	Cross-sectional (all outcome measures will be collected within a 4 week period)
Urinary metabolomics	Urine samples will be used for metabolic profiling of excreted metabolites	Cross-sectional (all outcome measures will be collected within a 4 week period)
Microbiome analysis	Faecal samples will be used to analyse gut microbiota composition through the 16S ribosomal RNA gene sequencing technique	Cross-sectional (all outcome measures will be collected within a 4 week period)

Collaborators and Investigators

• Sponsor: Loughborough University
• Collaborators: University of Reading

Study record dates

Study Major Dates

• Study Start (Actual): March 21, 2019
• Primary Completion (Anticipated): March 1, 2022
• Study Completion (Anticipated): March 1, 2022

Study Registration Dates

• First Submitted: February 14, 2019
• First Submitted That Met QC Criteria: March 5, 2019
• First Posted (Actual): March 6, 2019

Study Record Updates

• Last Update Posted (Actual): February 24, 2021
• Last Update Submitted That Met QC Criteria: February 23, 2021
• Last Verified: February 1, 2021

More Information

Terms related to this study

• Keywords: Gut Microbiota; Glycaemic Control; Metabolic Health; Gut Permeability; Metabolic Endotoxemia
• Additional Relevant MeSH Terms: Pathologic Processes; Glucose Metabolism Disorders; Metabolic Diseases; Infections; Systemic Inflammatory Response Syndrome; Overnutrition; Nutrition Disorders; Overweight; Body Weight; Sepsis; Hyperinsulinism; Bacteremia; Toxemia; Obesity; Inflammation; Metabolic Syndrome; Insulin Resistance; Endotoxemia
• Other Study ID Numbers: R18-P206

Drug and device information, study documents

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