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

ObjectiveTo 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). DesignAn 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. ResultsForty-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. ConclusionA food-based VLED, with more whole food components and fewer highly processed industrial ingredients, increases gut microbiome diversity more than a supplement-based VLED. Summary BoxWhat is already known on this topic Dietary interventions can alter gut microbiome composition, but the impact of food processing, including in nutritionally balanced very low energy diets (VLEDs), is less understood. What this study adds This study shows that 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. How this study might affect research, practice, or policy. Summarise the implications of this study Our findings underscore the need for further research into how specific components and attributes of diets, both including and beyond nutritional composition, influence the gut microbiome.