Our gut microbiome plays an important role in the etiology of obesity and obesity-related disorders. The colonic microbiota ferments indigestible dietary fibers and proteins, yielding saccharolytic products (e.g. short-chain fatty acids (SCFA)) or proteolytic products (branched-chain fatty acids, BCFA) that, respectively, positively or negatively affect human metabolic, gut and brain health. We previously demonstrated that acute SCFA infusion to the distal, but not the proximal, colon, has positive effects on human substrate and energy metabolism. Here, we hypothesize that a fibre mixture that increases distal saccharolytic fermentation, thereby inhibiting distal proteolytic fermentation, increases distal SCFA production and improves metabolic, immune and brain health.

The aim of this project is, firstly, to define a complex fiber mixture that increases saccharolytic and reduces proteolytic fermentation throughout the colon and, secondly, to study the impact of this microbial substrate switch on metabolic, immune and brain health.

 First, we carried out in vitro experiments using the TIM-2 model, a computer-controlled dynamic model simulating colonic fermentation, using a standardized pooled microbiota from individuals with overweight/obesity and insulin resistance (resembling the target population of the clinical trial). Potato fiber, chicory inulin and sugar beet pectin were tested separately and in different combinations against a high protein background. The combination of potato fiber and sugar beet pectin showed the highest distal SCFA to BCFA production ratio.

 This fiber combination will be tested in vivo in a double-blind, randomized, placebo-controlled trial in 44 humans with overweight (BMI 28-40kg/m²) and insulin resistance (Fasting glucose 5.6-6.9mmol/l; HbA1c 42-47mmol/mol; HOMA-IR>2.2). This 12-week intervention consists of fiber (15g) or maltodextrin placebo ingestion against a high-protein background (25E%, 45% plant-based). Primary outcome will be the change in peripheral insulin sensitivity. Furthermore, hepatic and adipose tissue insulin sensitivity, inflammatory profile, microbiome composition and functionality, and neurocognitive functioning will be analyzed.

Research related to this abstract was funded by the Dutch Research Council (NWO) and the Carbohydrate Competence Center (CCC).