Precision Microbiome Modulation with Discrete Dietary Fiber Structures Directs Short-Chain Fatty Acid Production

Dietary fibers (DFs) impact the gut microbiome in ways often considered beneficial. However, it is unknown if precise and predictable manipulations of the gut microbiota, and especially its metabolic activity, can be achieved through DFs with discrete chemical structures. Using a dose-response trial with three type-IV resistant starches (RS4s) in healthy humans, we found that crystalline and phosphate cross-linked starch structures induce divergent and highly specific effects on microbiome composition that are linked to directed shifts in the output of either propionate or butyrate. The dominant RS4-induced effects were remarkably consistent within treatment groups, dose-dependent plateauing at 35 g/day, and can be explained by substrate-specific binding and utilization of the RS4s by bacterial taxa with different pathways for starch metabolism. Overall, these findings support the potential of using discrete DF structures to achieve targeted manipulations of the gut microbiome and its metabolic functions relevant to health. [Display omitted] •Small differences in DF structure distinctly affect the gut microbiome•Discrete DF structures can direct SCFA output toward either butyrate or propionate•Dominant effects of DF are dose-dependent and plateau at a daily dose of 35 g/day•While all responses were individualized, dominant effects were remarkably consistent Deehan et al. show that chemically modified resistant starches with small structural differences induce divergent and highly specific effects on the gut microbiome that direct changes in the output of either propionate or butyrate. Dominant effects were remarkably consistent within treatment groups and dose-dependent with a plateau at 35 g.