Effects of a slowly fermentable fiber mixture against the background of a high-protein diet on insulin sensitivity and metabolic health in individuals with overweight: a randomized, placebo-controlled trial.

The gut microbiota ferments dietary fibers, producing short-chain fatty acids (SCFA). Enhanced SCFA production in the distal colon has been linked to improved cardiometabolic health. However, most fibers are fermented proximally, resulting in increased protein fermentation distally, producing metabolites putatively harmful to metabolic health. This 12-week randomized, placebo-controlled trial aimed to improve metabolic health through increasing distal SCFA production while inhibiting proteolytic fermentation using a fiber supplement that increased distal SCFA production in vitro. We assessed the effects of daily potato fiber/sugar beet pectin supplementation (fiber, n = 19) versus maltodextrin (placebo, n = 21), both added to a high-protein diet (25E% protein, ±45% plant-based), on peripheral insulin sensitivity (IS) in adults with overweight/obesity. Secondary outcomes included tissue-specific IS, body composition, microbial composition and functionality, substrate metabolism, and gut permeability. Peripheral IS tended to decrease after fiber supplementation compared to placebo (p = 0.081), while whole-body IS significantly decreased (p = 0.034). Fiber mitigated the increase in insulin-mediated carbohydrate oxidation (p = 0.027) and decrease in fat oxidation (p = 0.006) that occurred in the placebo group. Additionally, fiber prevented an increase in protein oxidation (p = 0.048), while increasing colonic gut permeability (p = 0.046) and plasma interleukin-6 (p = 0.025). Body composition, microbial composition, and fecal and circulating metabolites remained unchanged. In conclusion, fibers combined with a high-protein diet reduced (peripheral) IS and decreased metabolic flexibility compared to placebo. Reduced protein oxidation after fiber may reflect diminished amino acid bioavailability. Additionally, coadministration of fiber and protein may compromise gut barrier function and inflammatory responses. More research investigating the interplay between dietary fibers and proteins is needed.