The effects of food-based versus supplement-based very low-energy diets on gut microbiome composition and health outcomes in women with high body mass index (The MicroFit Study): a randomised controlled trial

Objective: To compare the effects of consuming food-based versus supplement-based very low-energy diet (VLED) programs on gut microbiome composition in women with a high body mass index (BMI). Design: An investigator-initiated, single-blind, two-arm, parallel-group randomised controlled-feeding trial with computer-generated 1:1 randomisation. From May 2021 to February 2022, women aged 30-65 years with BMI 30-45 kg/m2 were recruited from southwest Victoria, Australia, and randomised to a three-week food-based or supplement-based VLED program. The primary outcome was between-group differential change in faecal microbiome alpha diversity (Shannon index) from baseline to week three, assessed using shotgun metagenomics. Outcome assessors, study investigators, and analysing statisticians were blinded to group allocation until analysis completion. Allocation concealment was managed by an independent researcher using a computer software system. Modified intention-to-treat (mITT) analyses using linear mixed-effects regression models estimated mean between-group differential changes, reported as beta-coefficient point estimates ({beta}) and 95% confidence intervals (95%CI), adjusted for multiple comparisons. Results: Forty-seven participants were randomised (food-based: n=23, supplement-based: n=24). Of the 45 participants analysed, there was a between-group differential change in the Shannon index (mITT {beta}: 0.37, 95%CI: 0.15 to 0.60) from baseline to week three, with a greater increase in the food-based group (mean change: 0.26, 95%CI: 0.09 to 0.44; n=23) versus supplement-based group (mean change: -0.10, 95%CI: -0.25 to 0.05; n=22). There were 27 non-serious adverse events (food-based: 8, supplement-based: 19), all non-serious. Conclusion: A food-based VLED, with more whole food components and fewer highly processed industrial ingredients, increases gut microbiome diversity more than a supplement-based VLED.