Aging and Gastrointestinal Barrier Function
Study Details
Study Description
Brief Summary
The purpose of this study is to assess the gastrointestinal responses of the elderly during hyperthermia.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
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Detailed Description
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.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Younger participants Individuals aged 18-39 years |
Other: Controlled hyperthermia
Individuals will be exposed to a control trial (no hyperthermia) and a controlled hyperthermia trial.
|
| Older participants Individuals aged over 65 years |
Other: Controlled hyperthermia
Individuals will be exposed to a control trial (no hyperthermia) and a controlled hyperthermia trial.
|
Outcome Measures
Primary Outcome Measures
- Gastrointestinal permeability before hyperthermia [Day 1: 3-5 hours after ingestion of multiple sugar drink.]
In vivo gastrointestinal permeability measured by quantities of orally ingested multi-sugar drink excreted in urine.
- Gastrointestinal permeability after hyperthermia [Day 2: 3-5 hours after ingestion of multiple sugar drink.]
In vivo gastrointestinal permeability measured by quantities of orally ingested multi-sugar drink excreted in urine.
Secondary Outcome Measures
- Microbiota diversity at baseline [Day 1: Control trial]
Fecal samples will be used for next-generation sequencing and analyzed for diversity.
- Bacterial species - at baseline [Day 1: Control trial]
Fecal samples will be used for next-generation sequencing and analyzed for bacterial species.
- Microbial translocation [Day 2: Directly before and immediately after the controlled hyperthermia]
Venous blood samples will be used for next-generation sequencing and analyzed for bacterial species.
- Systemic inflammation [Day 2: Directly before and immediately after the controlled hyperthermia]
Venous blood samples will be assessed for systemic pro-inflammatory markers a) tumor necrosis factor alpha, interleukin 6, and soluble cd14 receptor.
- Gastrointestinal blood flow [Day 2: Directly before and immediately after the controlled hyperthermia]
Gastrointestinal blood flow will be measured by analysing the flow of blood in the superior mesenteric artery using ultrasound
- Skin blood flow [Day 2: Before and continuously during controlled hyperthermia]
Skin blood flow will be measured using laser doppler flowmetry
Eligibility Criteria
Criteria
Inclusion Criteria:
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Healthy male and female individuals
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18-35 years or 65+ years of age
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Free of any underlying moderate to serious medical conditions
Exclusion Criteria:
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Known heart disease
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Any chronic medical conditions requiring regular medical therapy including cancer, diabetes, uncontrolled hypertension, inflammatory bowel disease, and uncontrolled hypercholestrolmia etc;
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Abnormality detected on routine screening suggestive of provocable ischemia or previously undetected cardiac disease or resting left bundle branch block on screening electrocardiogram.
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Current smokers, as well as individuals who regularly smoked within the past 3 years
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Subject with a body mass index ≥35 kg/m2
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Pregnant
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Chronic fatigue syndrome
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Use of immunosuppressant drugs within last 4 weeks prior to screening
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Diagnosed psychiatric disease
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Use of antibiotics or antimicrobial medication in last month
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Any previous abdominal surgery
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Use of steroids in last 6 weeks
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Regular use of probiotics in last month
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Use of laxatives or anti-diarrhetic in last month
Contacts and Locations
Locations
No locations specified.Sponsors and Collaborators
- University of Texas Southwestern Medical Center
Investigators
- Principal Investigator: Craig G Crandall, Ph.D., University of Texas Southwestern Medical Center
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- STU-2023-0171