Salmon Intake and Gut Health in Adults

Study Overview
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Brief Summary
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The overall objective of this project is to determine the interplay of salmon as a whole food and its bioactive compound astaxanthin on gut microbiome, fecal metabolome, and inflammation in obese prediabetic individuals. Our central hypothesis is that dietary bioactive astaxanthin in the form of whole food salmon will effectively reduce inflammation in obese prediabetic individuals, and favorably change the gut microbiota composition and diversity. The investigators anticipate that these changes will result in improved metabolic outcomes in obesity and type 2 diabetes. The two primary aims include: Aim 1: Assess the anti-inflammatory effect of the salmon dietary intervention and the underlying mechanisms on the change in plasma levels of inflammatory cytokines important for the host immune response. Aim 2: Identify whether the relationship between salmon consumption and decreased inflammation is mediated by the gut microbiome.

Detailed Description
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The goal of this project is to determine whether increased intake of salmon as a whole food and its bioactive compound astaxanthin has a causal impact on preventing inflammation by promoting human gut microbiome homeostasis. Findings from this study will provide new insights into maintenance of gut microbiome and will inform effective dietary recommendations and interventions, thereby reducing inflammation-associated diseases in humans. Aim: Evaluate the anti-inflammatory properties of astaxanthin-enriched salmon via re-balancing of human gut microbiome in obese prediabetic human subjects. The investigators will use a randomized, double-blind, crossover feeding study with 15 obese prediabetic males and 15 obese prediabetic females (n=30) . Participants will consume two servings (3 oz per serving) of wild salmon (intervention 1) and farmed salmon (intervention 2) daily in random orders. Each intervention is 4 weeks long and the washout duration between the two interventions is 5 weeks. Primary outcomes will be determined by measuring the inflammatory response and gut microbiota composition.

Official Title
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Salmon Intake and Gut Health in Adults

Conditions
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Gut Microbiome, Inflammation

Intervention / Treatment
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* Other: Wild Salmon
* Other: Farmed Salmon


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Males and non-pregnant, non-lactating pre-menopausal females BMI 30-40 kg/m2 Fasting blood glucose (without blood glucose-lowering drug) between 100-125 mg/dL Plasma total cholesterol ≤ 250 mg/dL, plasma triglyceride level ≤ 250 mg/Dl Age 30-50 years Weight stable over the last 3 months (< 2% body weight change) Sedentary and stable physical activity regimen 3 months prior (≤3 h/wk of moderate or high intensity exercise, resistance or aerobic training) Medication use stable for 6 months prior, and not include anti-inflammatory drugs (e.g. ibuprofen, aspirin) Not taking a carotenoid-containing or metabolism-altering supplement for the last 1 month, or have autoimmune diseases, and other malabsorptive disorders (including Crohn's, ileus or ulcerative colitis), liver or kidney insufficiency, allergies to tomatoes No current special diets or nutrient supplements, pre- or probiotics ( 3 months) No tobacco smoking Limited consumption of alcoholic beverages ≤ 1/d No frequent habitual consumption of salmon or other astaxanthin-rich foods. Exclusion Criteria: Pregnant, lactating, or menopausal females BMI < 30 or >40 kg/m2 Fasting blood glucose <100 or >125 mg/dL; or taking blood glucose lowering medication Plasma total cholesterol >250 mg/dL, plasma triglyceride level >250 mg/Dl Age <30 or >50 years 2% body weight change over the last 3 months >3 h/wk of moderate or high intensity exercise, resistance or aerobic training for the 3 months prior Changing medications in the past 6 months Taking anti-inflammatory drugs (e.g. ibuprofen, aspirin), carotenoid-containing or metabolism-altering supplements (for the last 1 month), or have autoimmune diseases, and other malabsorptive disorders (including Crohn's, ileus or ulcerative colitis), liver or kidney insufficiency, or allergies to tomatoes Currently on a special diet or taking nutrient supplements, pre- or probiotics ( 3 months) Tobacco smoking >1/d consumption of alcoholic beverages Frequent habitual consumption of salmon or other astaxanthin-rich foods.

Ages Eligible for Study
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Minimum Age: 30 Years
Maximum Age: 50 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Wild Salmon<br>Wild salmon fillets in a raw form | Other: Wild Salmon<br>* Wild salmon fillets<br>|
| Experimental: Farmed Salmon<br>Farmed salmon fillets in a raw form | Other: Farmed Salmon<br>* Farm salmon fillets<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Blood biomarkers/inflammatory cytokines | Blood from patients will be processed via centrifugation to archive plasma. A panel of 48 factors from Bio-Rad (Bio-Plex Pro™ Human Cytokine Screening Panel, 48-Plex #12007283) will be measured in plasma by Bio-Rad Bio-Plex analyzer. Five primary biomarkers (IL-1β, IL-6, IL-10, TNF-α, and MCP-1) will be confirmed by traditional ELISA | Over 32 weeks | 
| Gut Microbiome | Gut microbiota structure by 16S sequencing | Over 32 weeks | 
| Fecal metabolomics | Small molecules will be extracted using MTBE-based liquid:liquid extraction which results in lipid and aqueous fractions. Compounds will be extracted using commercial software (Mass Hunter, Agilent), quantitated using peak volumes and processed using Mass Profiler Professional (MPP, Agilent) to determine normalized compound intensities | Over 32 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Urine Analysis | Urine samples will be collected for future metabolomics analysis. This analysis will generate a metabolomics profile in biospecimens, which will help us identify potential signatures related to salmon intake | Over 32 weeks |