The GUT-BRAIN study: Short-term effect of a high-fiber diet on gut-brain communication

Background. Based on recent experimental neuroscientific studies, it has been suggested that high-fiber diets, rich in naturally occurring prebiotics such as soluble fibers, might affect brain structure and functions through changes in the gut microbiome. However, due to a lack of evidence from randomized controlled trials in humans, it remains to be shown whether fibers affect brain structure and cognitive function through “bottom-up” metabolic mechanisms via the gut-brain axis. Aim. We therefore aim to elucidate whether there is a causal link between diet, gut microbial signalling and the brain. To do so, we are conducting a double-blind within-subject cross-over dietary intervention study with inulin as high-fiber supplement versus placebo. This study includes the analysis of blood-based biomarkers and stool-derived microbiota composition, as well as the assessment of task-based brain activation in food decision making and memory performance. Hypotheses. We hypothesize that supplementary high-fiber compared to placebo intake modulates food wanting and memory performance and its neuronal correlates. We further presume that changes in the gut microbial composition (e.g. higher α- and β-diversity) and in carbohydrate-specific metabolic pathways (e.g. short-chain fatty acid synthesis) may mediate potential effects of the high-fiber diet. Methods. Each participant (ntotal = 60, 18-45 years old) takes part in five experiment days out of which four include MRI sessions (Siemens Magnetom Prisma 3T) directly before and after the dietary intervention/placebo period. As dietary intervention, participants take 30g of inulin supplement (extracted from the chicory plant) daily for two weeks or a calorie-matched placebo supplement (maltodextrin) while maintaining their usual omnivorous diet. Food wanting and memory performance and related brain activity are assessed using functional magnetic resonance imaging (fMRI, 3T, TR 2000ms, 2mm³ isotropic). Briefly, participants have to indicate wanting of different food and, as contrast condition, art stimuli on an 8-point Likert scale. Memory performance is assessed after a delay of 20 minutes (fMRI) and after 12 weeks (behaviour). We further collect structural and diffusion-weighted images. Besides brain imaging, participants perform the Attentional Network Test. In addition, we monitor anthropometry, metabolic and emotional health makers with blood samples and questionnaires (e.g. WHO 5, BDI-II, GQLI, PANAS) as well as fecal samples to characterize microbial diversity (16S rRNA gene sequencing) and metabolic activity. Conclusions. This randomized controlled trial comprehensively determines the effects of a high-fiber dietary intervention on food wanting and neuronal correlates and whether these effects are mediated by changes in gut microbial composition and metabolism. Advantages of the study design are the within-subject contrasts which account for the large inter-individual differences in gut microbial composition and in the evaluation of food items. Further, we thoroughly control for hunger state, personal characteristics and other confounders. Art pictures as non-food control stimuli showed consistent activation of brain-areas related to wanting evaluation. Therefore, we propose our fMRI task as a robust and reliable tool to evaluate specific aspects of food wanting against other reward dimensions. This study will help to elucidate whether high-fiber diets affect body and brain and which underlying mechanisms mediate these effects