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.

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.

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.