Abstract MP16: A Behavioral Weight-loss Intervention, But Not Metformin, Decreases A Marker Of Gut Barrier Permeability In Adult Cancer Survivors With Overweight Or Obesity

Abstract

Background: Serum lipopolysaccharide-binding protein (LBP), a surrogate biomarker for gut barrier permeability, is higher in adults with obesity and type 2 diabetes and may trigger inflammation. It is unknown whether a behavioral weight loss intervention or metformin — current first-line treatments for obesity or diabetes — can reduce gut permeability. Objective: To determine the effects of behavioral weight loss intervention or metformin, compared to self-directed weight loss, on serum LBP. Methods: SPIRIT was a parallel-arm, randomized trial of adult cancer survivors with overweight or obesity. Participants were randomized to a self-directed weight loss (control), metformin, or coach-directed (healthy diet/physical activity) weight loss arm. Of 121 randomized participants, a random subset (n=88) had LBP measured at baseline, 6-months, and 12-months post intervention. The effects of interventions on LBP over time were assessed using generalized estimating equations (GEE). Models were further adjusted for absolute change in fiber intake to investigate potential mediation. Results: Arms were balanced by sex (83% female), race (48% black), and age (mean 60 years). There were no between-group differences in LBP at baseline (median 42.3 μg/dL). Over the 12-month period, only the coach-directed and metformin arms showed weight loss (both mean -3% from baseline). Similar increases in LBP were seen in the self-directed and metformin arms, while a decrease in LBP was seen in the coach-directed arm ( figure ). In GEE models, the difference in slopes between the coach vs. self-directed arms was statistically significant (β=-1.67, p=0.037), but not between the metformin and self-directed arms (β=0.003, p=0.997). The effect of coach-directed weight loss on LBP was similar by sex and race and was not mediated by changes in fiber intake. Conclusion: The manner of weight loss can differentially impact gut permeability and thus subsequent exposure to proinflammatory microbial products.