A behavioral weight-loss intervention, but not metformin, decreases a marker of gut barrier permeability: results from the SPIRIT randomized trial

Background/objectives: Lipopolysaccharide-binding protein (LBP), a biomarker of gut barrier permeability to lipopolysaccharides, is higher in adults with obesity and type 2 diabetes. Behavioral weight loss and metformin have distinct effects on the gut microbiome, but their impact on gut permeability to lipopolysaccharides is unknown. This study’s objective was to determine the effects of a behavioral weight-loss intervention or metformin treatment on plasma LBP. Subjects/methods: SPIRIT was a randomized trial of adults with overweight or obesity. Participants were randomized to one of three arms: metformin treatment, coach-directed behavioral weight loss on a DASH diet, or self-directed care (control). Of 121 participants, a random subset (n = 88) was selected to have LBP measured at baseline, 6 months, and 12 months post intervention. Intervention effects on LBP over time were assessed using generalized estimating equations (GEE). We also examined whether the intervention effects were modified by change in diet and weight. Results: Arms were balanced by sex (83% female), race (51% white), and age (mean 60 years), with no differences in baseline LBP (median 4.23 μg/mL). At 1 year, mean weight change was −3.00% in the metformin arm, −3.02% in the coach-directed behavioral weight-loss arm, and +0.33% in the self-directed (control) arm. The corresponding change in LBP was +1.03, −0.98, +1.03 μg/mL. The behavioral weight-loss intervention reduced LBP compared to self-directed care (β = −0.17, 95% CI: −0.33 to −0.01); no other between-arm comparisons were significant. Behavioral weight-loss participants who reduced dietary fat showed the greatest reductions in 6-month LBP (β = −2.84, 95% CI: −5.17 to −0.50). Conclusions: Despite similar weight loss in the behavioral weight loss arm and the metformin arm, only the behavioral weight-loss intervention reduced LBP compared to control. Lifestyle weight-loss interventions that promote a DASH diet may be effective at reducing gut barrier permeability to lipopolysaccharides. Clinical trials registration number: NCT02431676, https://clinicaltrials.gov