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Clinical Research

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

International Journal of Obesity volume 46, pages 655–660 (2022)Cite this article

Subjects

Abstract

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

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Fig. 1: Change in LBP distribution over time, by trial arm.
Fig. 2: Stratified 6-month change in LBP in the intervention arms vs. self-directed control arm.

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Data availability

Data described in the manuscript, code book, and analytic code will be made available upon reasonable request.

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Funding

The SPIRIT study was funded by the Maryland Cigarette Restitution Fund. NTM was supported by the National Heart, Lung, and Blood Institute of the National Institutes of Health (K01HL141589). HCY was supported in part by the National Cancer Institute’s Cancer Centers Support Grant to the Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins (5P30CA006973). CT was supported by the National Heart, Lung, and Blood Institute grant T32HL007024.

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Authors and Affiliations

  1. Department of Epidemiology, Johns Hopkins University Bloomberg School of Public Health, Baltimore, MD, USA

    Curtis Tilves & Noel T. Mueller

  2. Welch Center for Prevention, Epidemiology, and Clinical Research, Johns Hopkins University, Baltimore, MD, USA

    Curtis Tilves, Hsin-Chieh Yeh, Nisa Maruthur, Edgar R. Miller, Lawrence J. Appel & Noel T. Mueller

  3. Division of General Medicine and Primary Care, Beth Israel Deaconess Medical Center, Boston, MA, USA

    Stephen P. Juraschek

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  1. Curtis Tilves
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Contributions

Contributions (in alphabetical order): designed research: HCY, NTM. Conducted research: HCY, LJA, NTM. Performed statistical analysis: CT, NTM. Wrote paper: CT, NTM. Other—data interpretation and manuscript revision: CT, ERM, HCY, LJA, NM, NTM, SPJ.

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Correspondence to Noel T. Mueller.

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Tilves, C., Yeh, HC., Maruthur, N. et al. A behavioral weight-loss intervention, but not metformin, decreases a marker of gut barrier permeability: results from the SPIRIT randomized trial. Int J Obes 46, 655–660 (2022). https://doi.org/10.1038/s41366-021-01039-2

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