The effects of a powdered meal replacement intake on inflammation, gut microbiota, and metabolism compared to habitual diet in people with excess body weight – results from a randomized controlled trial

Excess body weight is associated with chronic low-grade inflammation and metabolic abnormalities, such as insulin resistance, and dyslipidemia. This study aimed to assess the impact of a soy protein-yogurt-honey powdered meal replacement (PMR) on inflammation, gut microbiota, and metabolism in individuals with excess body weight and in weight-stable conditions. The Premium Study was a 12-week, parallel-arm, randomized controlled trial. Participants (body mass index 25–37 kg/m 2 ) were randomized into either control (CON; usual diet, n=34) or PMR (two daily doses added to usual diet, n=29) groups, maintaining a stable body weight. Assessments occurred at baseline, week 6, and week 12, and included inflammation markers (primary outcome: interleukin-6 IL-6), gut microbiota diversity and composition (secondary outcome), metabolic blood markers (glucose and lipid profile), body composition (via dual-energy X-ray absorptiometry), and dietary intake. Data of completers was analyzed by two-way repeated measures analysis of variance or generalized estimating equations with Bonferroni-corrected post-hoc tests. Between-group differences in changes over time are expressed as mean and 95% confidence intervals. Adherence to PMR was 98% of total doses, which increased protein intake (6.53 5.04, 8.02%, p<0.001) and decreased fat intake (-5.23 -7.10, -3.35%, p<0.001) compared to CON. By design, body weight remained stable. There were no changes in IL-6 (0.01 -0.47, 0.45 pg/mL, p=0.412, with a low statistical power of 13.7%). Minor changes in gut microbiota composition included an increase in relative abundance of Subdoligranulum (0.72 Log 2 fold-change, q=0.002). In exploratory outcomes, PMR increased lean soft tissue (LST; 0.57 0.12, 1.02 kg, p=0.014) and reduced total cholesterol (-0.33 -0.58, -0.08 mmol/L, p=0.01) and low-density lipoprotein cholesterol (-0.28 -0.46, -0.10 mmol/L, p=0.003). In this population, PMR intake did not improve chronic low-grade inflammation and had limited effects on gut microbiota. Improvements in LST and lipid profile warrant further exploration. Number NCT03235804 registered on August 1 st , 2017: https://clinicaltrials.gov/study/NCT03235804.