Aging and Gastrointestinal Barrier Function

Study Overview
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Brief Summary
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The purpose of this study is to assess the gastrointestinal responses of the elderly during hyperthermia.

Detailed Description
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Heat waves are lethal and cause a disproportionate number of deaths in the elderly relative to any other age group. Although gastrointestinal barrier dysfunction is a primary cause of heat related illness, little is known about the effects of aging on gastrointestinal barrier function during hyperthermia. The central hypothesis of this work is that the elderly exhibit greater gastrointestinal barrier dysfunction during hyperthermia. Participants will complete a control trial where gastrointestinal permeability (without heating) will be assessed in young and older adults. In the experimental trial, controlled hyperthermia will be achieved using a water perfused, tube lined suit. Core body temperature will be raised to a maximum of 2 degrees Celsius above the baseline value, or an absolute temperature of 39.5 degrees Celsius. Comprehensive assessments of gastrointestinal barrier function, microbial translocation and systemic inflammation will be assessed in young and older adults. The expected outcome of this work will re-shape out understanding of the consequences of aging on gastrointestinal barrier function during heat waves.

Official Title
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Impact of Aging on Gastrointestinal Barrier Function During Hyperthermia

Conditions
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Hyperthermia, Aging

Intervention / Treatment
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* Other: Controlled hyperthermia


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Healthy male and female individuals 18-35 years or 65+ years of age Free of any underlying moderate to serious medical conditions Exclusion Criteria: Known heart disease Any chronic medical conditions requiring regular medical therapy including cancer, diabetes, uncontrolled hypertension, inflammatory bowel disease, and uncontrolled hypercholestrolmia etc; Abnormality detected on routine screening suggestive of provocable ischemia or previously undetected cardiac disease or resting left bundle branch block on screening electrocardiogram. Current smokers, as well as individuals who regularly smoked within the past 3 years Subject with a body mass index ≥35 kg/m2 Pregnant Chronic fatigue syndrome Use of immunosuppressant drugs within last 4 weeks prior to screening Diagnosed psychiatric disease Use of antibiotics or antimicrobial medication in last month Any previous abdominal surgery Use of steroids in last 6 weeks Regular use of probiotics in last month Use of laxatives or anti-diarrhetic in last month

Ages Eligible for Study
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Minimum Age: 18 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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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Younger participants<br>Individuals aged 18-39 years | Other: Controlled hyperthermia<br>* Individuals will be exposed to a control trial (no hyperthermia) and a controlled hyperthermia trial.<br>|
| Older participants<br>Individuals aged over 65 years | Other: Controlled hyperthermia<br>* Individuals will be exposed to a control trial (no hyperthermia) and a controlled hyperthermia trial.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Gastrointestinal permeability before hyperthermia | In vivo gastrointestinal permeability measured by quantities of orally ingested multi-sugar drink excreted in urine. | Day 1: 3-5 hours after ingestion of multiple sugar drink. | 
| Gastrointestinal permeability after hyperthermia | In vivo gastrointestinal permeability measured by quantities of orally ingested multi-sugar drink excreted in urine. | Day 2: 3-5 hours after ingestion of multiple sugar drink. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Microbiota diversity at baseline | Fecal samples will be used for next-generation sequencing and analyzed for diversity. | Day 1: Control trial | 
| Bacterial species - at baseline | Fecal samples will be used for next-generation sequencing and analyzed for bacterial species. | Day 1: Control trial | 
| Microbial translocation | Venous blood samples will be used for next-generation sequencing and analyzed for bacterial species. | Day 2: Directly before and immediately after the controlled hyperthermia | 
| Systemic inflammation | Venous blood samples will be assessed for systemic pro-inflammatory markers a) tumor necrosis factor alpha, interleukin 6, and soluble cd14 receptor. | Day 2: Directly before and immediately after the controlled hyperthermia | 
| Gastrointestinal blood flow | Gastrointestinal blood flow will be measured by analysing the flow of blood in the superior mesenteric artery using ultrasound | Day 2: Directly before and immediately after the controlled hyperthermia | 
| Skin blood flow | Skin blood flow will be measured using laser doppler flowmetry | Day 2: Before and continuously during controlled hyperthermia |