Salmon Intake and Gut Health in Adults

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.

Study Overview

• Status: Completed
• Conditions: Inflammation; Gut Microbiome
• Intervention / Treatment: Other: Wild Salmon; Other: Farmed Salmon

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 40
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Colorado
    • Aurora, Colorado, United States, 80045
      • University of Colorado Anschutz Medical Campus

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 30 years to 50 years (Adult)
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Wild Salmon; Wild salmon fillets in a raw form	Other: Wild Salmon; Wild salmon fillets
Experimental: Farmed Salmon; Farmed salmon fillets in a raw form	Other: Farmed Salmon; Farm salmon fillets

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: University of Colorado, Denver

Study record dates

Study Major Dates

• Study Start (Actual): August 1, 2021
• Primary Completion (Actual): April 3, 2023
• Study Completion (Actual): April 30, 2023

Study Registration Dates

• First Submitted: March 8, 2021
• First Submitted That Met QC Criteria: March 8, 2021
• First Posted (Actual): March 10, 2021

Study Record Updates

• Last Update Posted (Estimated): November 19, 2024
• Last Update Submitted That Met QC Criteria: November 14, 2024
• Last Verified: November 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Inflammation
• Other Study ID Numbers: 20-1033

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

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