(P30-037-24) Study Protocol: Microbial and Metabolic Impact of Walnut Consumption in Adults With Obesity

Objectives: The intestinal microbiome may mediate the metabolic effects of obesity, including systemic inflammation (SI) and insulin resistance. Our prior research found that walnuts, high in fiber and unsaturated fatty acids, reduced fecal secondary bile acids (BA) and increased Faecalibacterium spp. and Roseburia spp., butyrate-producing bacteria linked to reduced gut inflammation and improved glucose tolerance. Our central hypothesis is that walnut consumption increases Faecalibacterium spp., Roseburia spp., and butyrate concentrations and decreases secondary BA compared to the control groups (corn oil and walnut oil), which in turn reduces SI with subsequent improvements in whole-body insulin sensitivity.

Methods: This was a randomized, controlled, crossover, complete feeding trial with three 3-week diet conditions, each identical except for the daily inclusion of walnut halves (WH), walnut oil (WO), or corn oil (CO) in the diet. A 3-week washout separated each condition. Adults (n=30) with obesity (BMI ≥ 30 kg/m2; 25-75 y) without diabetes or gastrointestinal diseases were enrolled. Fecal samples were collected between days 18 and 20 of each condition. On day 20, participants underwent a mixed meal tolerance test. Fasting blood was collected at t=0 min; participants ingested a 75g glucose beverage and the treatment (WH, WO, or CO); blood samples were collected at t=30, 60, 90, 120, 180, 240, 270, 300, 330, and 360 min. Fecal microbiome was assessed using metagenomic sequencing, and microbial metabolites were quantified via gas chromatography (GC). For blood analysis, glucose concentrations, insulin resistance (HOMA-IR), insulin sensitivity (Matsuda Index), and inflammatory biomarkers (LPS-BP, IL-6, TNFα, and CRP) will be measured. Fecal and circulating BA will be measured via GC. Regional and whole-gut intestinal permeability will be assessed by measuring urinary excretion of ingested sugar substitutes on day 21 of each condition.

Results: N/A

Conclusions: We expect that walnut consumption will lead to beneficial shifts in the intestinal microbiome and metabolome, contributing to reduced SI and improvements in metabolic status.

Funding Sources: This work is supported by the Agriculture and Food Research Initiative grant no. 2020-67017-30836/project accession no. 1021932 from the USDA National Institute of Food and Agriculture and the CONACYT of Mexico.