Background: Dietary fiber is an integral part of a healthy diet, but questions remain about the mechanisms that underlie effects and the causal contributions of the gut microbiota. Here, we performed a 6-week exploratory trial in adults with excess weight (BMI: 25–35 kg/m²) to compare the effects of a high-dose (females: 25 g/day; males: 35 g/day) supplement of fermentable corn bran arabinoxylan (AX;n= 15) with that of microbiota-non-accessible microcrystalline cellulose (MCC;n= 16). Obesity-related surrogate endpoints and biomarkers of host-microbiome interactions implicated in the pathophysiology of obesity (trimethylamineN-oxide, gut hormones, cytokines, and measures of intestinal barrier integrity) were assessed. We then determined whether clinical outcomes could be predicted by fecal microbiota features or mechanistic biomarkers.Results: AX enhanced satiety after a meal and decreased homeostatic model assessment of insulin resistance (HOMA-IR), while MCC reduced tumor necrosis factor-α and fecal calprotectin. Machine learning models determined that effects on satiety could be predicted by fecal bacterial taxa that utilized AX, as identified by bioorthogonal non-canonical amino acid tagging. Reductions in HOMA-IR and calprotectin were associated with shifts in fecal bile acids, but correlations were negative, suggesting that the benefits of fiber may not be mediated by their effects on bile acid pools. Biomarkers of host-microbiome interactions often linked to bacterial metabolites derived from fiber fermentation (short-chain fatty acids) were not affected by AX supplementation when compared to non-accessible MCC.Conclusion: This study demonstrates the efficacy of purified dietary fibers when used as supplements and suggests that satietogenic effects of AX may be linked to bacterial taxa that ferment the fiber or utilize breakdown products. Other effects are likely microbiome independent. The findings provide a basis for fiber-type specific therapeutic applications and their personalization.Trial registration: Clinicaltrials.gov,NCT02322112, registered on July 3, 2015.

Introduction Excess body weight is associated with a state of low-grade chronic inflammation and alterations of the gut microbiome. Powdered meal replacements (PMR) have been shown to be an effective strategy for weight management; however, their effect on inflammation and the gut microbiome remains unclear. The aim of this 12-week randomised control clinical trial is to investigate the effects of PMR consumption, here given as a soy-yoghurt-honey formula, on inflammation, gut microbiome and overall metabolism in individuals with excessive body weight. Methods and analysis Healthy adults with excess body weight (n=88) are being recruited and randomly assigned to one of the following groups: (1) Control group (CON): maintaining usual diet for 12 weeks, or (2) PMR group: replacing morning and afternoon snacks daily with a PMR for 12 weeks. Participants are asked to maintain body weight throughout the study and fill out a journal with information about PMR consumption, body weight, food intake, appetite sensations and medications. Three study visits are required: baseline, week 6 and week 12. Outcome measures include systemic inflammatory biomarkers, gut microbiome composition, metabolic blood markers, host energy metabolism, body composition, appetite sensations and host gene expression profile. Ethics and dissemination This research protocol was approved by the University of Alberta Ethics Board (Pro00070712) and adheres to the Canadian Tri-Council Policy statement on the use of human participants in research. Procedures and potential risks are fully discussed with participants. Study findings will be disseminated in peer-reviewed journals, conference presentations and social media. Trial registration number NCT03235804.

Dietary fiber supplementation can reduce cardiometabolic risk, but its effective use is limited by incomplete understanding of fibre-microbiome interactions and highly individualized responses. We tested acacia gum (AG; fermentable fibre), resistant starch type 4 (RS4; fermentable fibre), and microcrystalline cellulose (MCC; non-fermentable control fibre) in a six-week randomized trial in adults with excess body weight. Multi-omics profiling revealed distinct, structure-specific microbiota and short-chain fatty acid shifts with AG and RS4, which were not directly linked to physiological outcomes. Improvements in inflammation, gut barrier function, and satiety occurred across all arms, indicating fermentation-independent effects. AG reduced plasma ghrelin, linked to microbial carbohydrate-active enzyme genes targeting its structures. Machine-learning models predicted individualized, fiber-specific effects on blood pressure (AG) and C-reactive protein (RS4) from microbial pathways and fecal bile acids. These findings delineate fermentation-dependent and independent mechanisms of fibre action and provide a mechanistic basis for personalized fibre supplementation. Trial registration: ClinicalTrials.gov NCT02322112

1. Development and modulation of the gut microbiome is shaped by factors including birthing mode and exposures, medications, lifestyle (including diet), environment, genetics, and age. 1-4 Once est...