Background
Our gut microbiota affects the cardiometabolic phenotype by fermenting dietary fibers which are coupled to production of short-chain fatty acids (SCFA). SCFA can affect adipose tissue function and ectopic fat storage thereby modulating host insulin resistance. Slowly fermentable fibers with a high degree of polymerization that increase SCFA specifically in the distal colon are expected to have higher potential for influencing host metabolism and metabolic health by improving insulin sensitivity.

Rationale
Previous research has shown that acute administration of SCFA in the distal colon has pronounced metabolic effects, whilst proximal infusion did not result in any metabolic effects. In this study we will supplement a unique fiber product extracted from chicory root containing cellulose, pectin and inulin. We hypothesize that this fiber product will ferment and produce SCFA in the whole colon (including the distal colon) and has pronounced effect on insulin sensitivity and metabolic health.

Methods
This 12-week randomized clinical trial aims to investigate the potential of the dietary fiber product on microbial composition and functionality, insulin sensitivity, inflammatory profile and human substrate energy metabolism in individuals with overweight or obesity and impaired glucose metabolism. 42 male and female adult volunteers will consume either placebo or the fiber product twice a day. Our primary outcome parameter is the change in peripheral insulin sensitivity assessed by the gold standard hyperinsulinemic-euglycemic clamp. Secondary parameters include body composition (DXA), liver fat content (¹H-MRS), hepatic and adipose tissue insulin sensitivity as well as circulating plasma markers including SCFA, insulin, glucagon, PYY, GLP-1 in addition to inflammatory markers. Fecal samples will be collected for microbial composition analysis (16SrRNA Illumina sequencing). Furthermore, feces will be collected anaerobically for mechanistic deepening in mice models (fecal transplants, collaboration Leiden University) as well as for in vitro fermentation experiments in the TIM-2 model (collaboration campus Venlo).

Conclusion
No results are currently available as the study is still ongoing. The expected date for the measurement of the last participant will be in August 2022. Overall, this project has potential to provide new and important insights into the link between nutrition, gut microbiota and its products and peripheral tissue insulin sensitivity in humans, which may provide important information for personalized nutritional strategies to prevent insulin resistance and chronic metabolic diseases.