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.

Study Overview
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Brief Summary
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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.

Official Title
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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.

Conditions
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Obesity, Metabolic Syndrome, Insulin Resistance

Participation Criteria
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Eligibility Criteria
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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)

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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What is the study measuring?
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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) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Glycaemic Control, Gut Permeability, Gut Microbiota, Metabolic Endotoxemia, Metabolic Health